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Literature review, alive program, implications for school social work practice.

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Trauma and Early Adolescent Development: Case Examples from a Trauma-Informed Public Health Middle School Program

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Jason Scott Frydman, Christine Mayor, Trauma and Early Adolescent Development: Case Examples from a Trauma-Informed Public Health Middle School Program, Children & Schools , Volume 39, Issue 4, October 2017, Pages 238–247, https://doi.org/10.1093/cs/cdx017

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Middle-school-age children are faced with a variety of developmental tasks, including the beginning phases of individuation from the family, building peer groups, social and emotional transitions, and cognitive shifts associated with the maturation process. This article summarizes how traumatic events impair and complicate these developmental tasks, which can lead to disruptive behaviors in the school setting. Following the call by Walkley and Cox for more attention to be given to trauma-informed schools, this article provides detailed information about the Animating Learning by Integrating and Validating Experience program: a school-based, trauma-informed intervention for middle school students. This public health model uses psychoeducation, cognitive differentiation, and brief stress reduction counseling sessions to facilitate socioemotional development and academic progress. Case examples from the authors’ clinical work in the New Haven, Connecticut, urban public school system are provided.

Within the U.S. school system there is growing awareness of how traumatic experience negatively affects early adolescent development and functioning ( Chanmugam & Teasley, 2014 ; Perfect, Turley, Carlson, Yohannan, & Gilles, 2016 ; Porche, Costello, & Rosen-Reynoso, 2016 ; Sibinga, Webb, Ghazarian, & Ellen, 2016 ; Turner, Shattuck, Finkelhor, & Hamby, 2017 ; Woodbridge et al., 2016 ). The manifested trauma symptoms of these students have been widely documented and include self-isolation, aggression, and attentional deficit and hyperactivity, producing individual and schoolwide difficulties ( Cook et al., 2005 ; Iachini, Petiwala, & DeHart, 2016 ; Oehlberg, 2008 ; Sajnani, Jewers-Dailley, Brillante, Puglisi, & Johnson, 2014 ). To address this vulnerability, school social workers should be aware of public health models promoting prevention, data-driven investigation, and broad-based trauma interventions ( Chafouleas, Johnson, Overstreet, & Santos, 2016 ; Johnson, 2012 ; Moon, Williford, & Mendenhall, 2017 ; Overstreet & Chafouleas, 2016 ; Overstreet & Matthews, 2011 ). Without comprehensive and effective interventions in the school setting, seminal adolescent developmental tasks are at risk.

This article follows the twofold call by Walkley and Cox (2013) for school social workers to develop a heightened awareness of trauma exposure's impact on childhood development and to highlight trauma-informed practices in the school setting. In reference to the former, this article will not focus on the general impact of toxic stress, or chronic trauma, on early adolescents in the school setting, as this work has been widely documented. Rather, it begins with a synthesis of how exposure to trauma impairs early adolescent developmental tasks. As to the latter, we will outline and discuss the Animating Learning by Integrating and Validating Experience (ALIVE) program, a school-based, trauma-informed intervention that is grounded in a public health framework. The model uses psychoeducation, cognitive differentiation, and brief stress reduction sessions to promote socioemotional development and academic progress. We present two clinical cases as examples of trauma-informed, school-based practice, and then apply their experience working in an urban, public middle school to explicate intervention theory and practice for school social workers.

Impact of Trauma Exposure on Early Adolescent Developmental Tasks

Social development.

Impact of Trauma on Early Adolescent Development

Traumatic experiences may create difficulty with developing and differentiating another person's point of view (that is, mentalization) due to the formation of rigid cognitive schemas that dictate notions of self, others, and the external world ( Frydman & McLellan, 2014 ). For early adolescents, the ability to diversify a single perspective with complexity is central to modulating affective experience. Without the capacity to diversify one's perspective, there is often difficulty differentiating between a nonthreatening current situation that may harbor reminders of the traumatic experience and actual traumatic events. Incumbent on the school social worker is the need to help students understand how these conflicts may trigger a memory of harm, abandonment, or loss and how to differentiate these past memories from the present conflict. This is of particular concern when these reactions are conflated with more common middle school behaviors such as withdrawing, blaming, criticizing, and gossiping ( Card, Stucky, Sawalani, & Little, 2008 ).

Encouraging cognitive discrimination is particularly meaningful given that the second social developmental task for early adolescents is the re-orientation of their primary relationships with family toward peers ( Henderson & Thompson, 2010 ). This shift may become complicated for students facing traumatic stress, resulting in a stunted movement away from familiar connections or a displacement of dysfunctional family relationships onto peers. For example, in the former, a student who has witnessed and intervened to protect his mother from severe domestic violence might believe he needs to sacrifice himself and be available to his mother, forgoing typical peer interactions. In the latter, a student who was beaten when a loud, intoxicated family member came home might become enraged, anxious, or anticipate violence when other students raise their voices.

Cognitive Development and Emotional Regulation

During normative early adolescent development, the prefrontal cortex undergoes maturational shifts in cognitive and emotional functioning, including increased impulse control and affect regulation ( Wigfield, Lutz, & Wagner, 2005 ). However, these developmental tasks can be negatively affected by chronic exposure to traumatic events. Stressful situations often evoke a fear response, which inhibits executive functioning and commonly results in a fight-flight-freeze reaction. If a student does not possess strong anxiety management skills to cope with reminders of the trauma, the student is prone to further emotional dysregulation, lowered frustration tolerance, and increased behavioral problems and depressive symptoms ( Iachini et al., 2016 ; Saltzman, Steinberg, Layne, Aisenberg, & Pynoos, 2001 ).

Typical cognitive development in early adolescence is defined by the ambiguity of a transitional stage between childhood remedial capacity and adult refinement ( Casey & Caudle, 2013 ; Van Duijvenvoorde & Crone, 2013 ). Casey and Caudle (2013) found that although adolescents performed equally as well as, if not better than, adults on a self-control task when no emotional information was present, the introduction of affectively laden social cues resulted in diminished performance. The developmental challenge for the early adolescent then is to facilitate the coordination of this ever-shifting dynamic between cognition and affect. Although early adolescents may display efficient and logically informed behaviors, they may struggle to sustain these behaviors, especially in the presence of emotional stimuli ( Casey & Caudle, 2013 ; Van Duijvenvoorde & Crone, 2013 ). Because trauma often evokes an emotional response ( Johnson & Lubin, 2015 ), these findings insinuate that those early adolescents who are chronically exposed will have ongoing regulation difficulties. Further empirical findings considering the cognitive effects of trauma exposure on the adolescent brain have highlighted detriments in working memory, inhibition, memory, and planning ability ( Moradi, Neshat Doost, Taghavi, Yule, & Dalgleish, 1999 ).

Using a Public Health Framework for School-Based, Trauma-Informed Services

The need for a more informed and comprehensive approach to addressing trauma within the schools has been widely articulated ( Chafouleas et al., 2016 ; Durlak, Weissberg, Dymnicki, Taylor, & Schellinger, 2011 ; Jaycox, Kataoka, Stein, Langley, & Wong, 2012 ; Overstreet & Chafouleas, 2016 ; Perry & Daniels, 2016 ). Overstreet and Matthews (2011) suggested that using a public health model to address trauma in schools will promote prevention, early identification, and data-driven investigation and yield broad-based intervention on a policy and communitywide level. A public health approach focuses on developing interventions that address the underlying causal processes that lead to social, emotional, and cognitive maladjustment. Opening the dialogue to the entire student body, as well as teachers and administrators, promotes inclusion and provides a comprehensive foundation for psychoeducation, assessment, and prevention.

ALIVE: A Comprehensive Public Health Intervention for Middle School Students

Note: ALIVE = Animating Learning by Integrating and Validating Experience.

Psychoeducation

The classroom is a place traditionally dedicated to academic pursuits; however, it also serves as an indicator of trauma's impact on cognitive functioning evidenced by poor grades, behavioral dysregulation, and social turbulence. ALIVE practitioners conduct weekly trauma-focused dialogues in the classroom to normalize conversations addressing trauma, to recruit and rehearse more adaptive cognitive skills, and to engage in an insight-oriented process ( Sajnani et al., 2014 ).

Using a parable as a projective tool for identification and connection, the model helps students tolerate direct discussions about adverse experiences. The ALIVE practitioner begins each academic year by telling the parable of a woman named Miss Kendra, who struggled to cope with the loss of her 10-year-old child. Miss Kendra is able to make meaning out of her loss by providing support for schoolchildren who have encountered adverse experiences, serving as a reminder of the strength it takes to press forward after a traumatic event. The intention of this parable is to establish a metaphor for survival and strength to fortify the coping skills already held by trauma-exposed middle school students. Furthermore, Miss Kendra offers early adolescents an opportunity to project their own needs onto the story, creating a personalized figure who embodies support for socioemotional growth.

Following this parable, the students’ attention is directed toward Miss Kendra's List, a poster that is permanently displayed in the classroom. The list includes a series of statements against adolescent maltreatment, comprehensively identifying various traumatic stressors such as witnessing domestic violence; being physically, verbally, or sexually abused; and losing a loved one to neighborhood violence. The second section of the list identifies what may happen to early adolescents when they experience trauma from emotional, social, and academic perspectives. The practitioner uses this list to provide information about the nature and impact of trauma, while modeling for students and staff the ability to discuss difficult experiences as a way of connecting with one another with a sense of hope and strength.

Furthermore, creating a dialogue about these issues with early adolescents facilitates a culture of acceptance, tolerance, and understanding, engendering empathy and identification among students. This fostering of interpersonal connection provides a reparative and differentiated experience to trauma ( Hartling & Sparks, 2008 ; Henderson & Thompson, 2010 ; Johnson & Lubin, 2015 ) and is particularly important given the peer-focused developmental tasks of early adolescence. The positive feelings evoked through classroom-based conversation are predicated on empathic identification among the students and an accompanying sense of relief in understanding the scope of trauma's impact. Furthermore, the consistent appearance of and engagement by the ALIVE practitioner, and the continual presence of Miss Kendra's list, effectively counters traumatically informed expectations of abandonment and loss while aligning with a public health model that attends to the impact of trauma on a regular, systemwide basis.

Participatory and Somatic Indicators for Informal Assessment during the Psychoeducation Component of the ALIVE Intervention

Notes: ALIVE = Animating Learning by Integrating and Validating Experience. Examples are derived from authors’ clinical experiences.

In addition to behavioral symptoms, the content of conversation is considered. All practitioners in the ALIVE program are mandated reporters, and any content presented that meets criteria for suspicion of child maltreatment is brought to the attention of the school leadership and ALIVE director. According to Johnson (2012) , reports of child maltreatment to the Connecticut Department of Child and Family Services have actually decreased in the schools where the program has been implemented “because [the ALIVE program is] catching problems well before they have risen to the severity that would require reporting” (p. 17).

Case Example 1

The following demonstrates a middle school classroom psychoeducation session and assessment facilitated by an ALIVE practitioner (the first author). All names and identifying characteristics have been changed to protect confidentiality.

Ms. Skylar's seventh grade class comprised many students living in low-income housing or in a neighborhood characterized by high poverty and frequent criminal activity. During the second week of school, I introduced myself as a practitioner who was here to speak directly about difficult experiences and how these instances might affect academic functioning and students’ thoughts about themselves, others, and their environment.

After sharing the Miss Kendra parable and list, I invited the students to share their thoughts about Miss Kendra and her journey. Tyreke began the conversation by wondering whether Miss Kendra lost her child to gun violence, exploring the connection between the list and the story and his own frequent exposure to neighborhood shootings. To transition a singular connection to a communal one, I asked the students if this was a shared experience. The majority of students nodded in agreement. I referred the students back to the list and asked them to identify how someone's school functioning or mood may be affected by ongoing neighborhood gun violence. While the students read the list, I actively monitored reactions and scanned for inattention and active avoidance. Performing both active facilitation of discussion and monitoring students’ reactions is critical in accomplishing the goals of providing quality psychoeducation and identifying at-risk students for intervention.

After inspection, Cleo remarked that, contrary to a listed outcome on Miss Kendra's list, neighborhood gun violence does not make him feel lonely; rather, he “doesn't care about it.” Slumped down in his chair, head resting on his crossed arms on the desk in front of him, Cleo's body language suggested a somatized disengagement. I invited other students to share their individual reactions. Tyreke agreed that loneliness is not the identified affective experience; rather, for him, it's feeling “mad or scared.” Immediately, Greg concurred, expressing that “it makes me more mad, and I think about my family.”

Encouraging a variety of viewpoints, I stated, “It sounds like it might make you mad, scared, and may even bring up thoughts about your family. I wonder why people have different reactions?” Doing so moved the conversation into a phase of deeper reflection, simultaneously honoring the students’ voiced experience while encouraging critical thinking. A number of students responded by offering connections to their lives, some indicating they had difficulty identifying feelings. I reflected back, “Sometimes people feel something, but can't really put their finger on it, and sometimes they know exactly how they feel or who it makes them think about.”

I followed with a question: “How do you think it affects your schoolwork or feelings when you're in school?” Greg and Natalia both offered that sometimes difficult or confusing thoughts can consume their whole day, even while in class. Sharon began to offer a related comment when Cleo interrupted by speaking at an elevated volume to his desk partner, Tyreke. The two began to snicker and pull focus. By the time they gained the class's full attention, Cleo was openly laughing and pushing his chair back, stating, “No way! She DID!? That's crazy”; he began to stand up, enlisting Tyreke in the process. While this disruption may be viewed as a challenge to the discussion, it is essential to understand all behavior in context of the session's trauma content. Therefore, Cleo's outburst was interpreted as a potential avenue for further exploration of the topic regarding gun violence and difficulties concentrating. In turn, I posed this question to the class: “Should we talk about this stuff? I wonder if sometimes people have a hard time tolerating it. Can anybody think of why it might be important? Sharon, I think you were saying something about this.” While Sharon continued to share, Cleo and Tyreke gradually shifted their attention back to the conversation. I noted the importance of an individual follow-up with Cleo.

Natalia jumped back in the conversation, stating, “I think we talk about stuff like this so we know about it and can help people with it.” I checked in with the rest of the class about this strategy for coping with the impact of trauma exposure on school functioning: “So it sounds like these thoughts have a pretty big impact on your day. If that's the case, how do you feel less worried or mad or scared?” Marta quickly responded, “You could talk to someone.” I responded, “Part of my job here is to be a person to talk to one-on-one about these things. Hopefully, it will help you feel better to get some of that stuff off your chest.” The students nodded, acknowledging that I would return to discuss other items on the list and that there would be opportunities to check in with me individually if needed.

On reflection, Cleo's disruption in the discussion may be attributed to his personal difficulty emotionally managing intrusive thoughts while in school. This clinical assumption was not explicitly named in the moment, but was noted as information for further individual follow-up. When I met individually with Cleo, Cleo reported that his cousin had been shot a month ago, causing him to feel confused and angry. I continued to work with him individually, which resulted in a reduction of behavioral disruptions in the classroom.

In the preceding case example, the practitioner performed a variety of public health tasks. Foremost was the introduction of how traumatic experience may affect individuals and their relationships with others and their role as a student. Second, the practitioner used Miss Kendra and her list as a foundational mechanism to ground the conversation and serve as a reference point for the students’ experience. Finally, the practitioner actively monitored individual responses to the material as a means of identifying students who may require more support. All three of these processes are supported within the public health framework as a means toward assessment and early intervention for early adolescents who may be exposed to trauma.

Individualized Stress Reduction Intervention

Students are seen for individualized support if they display significant externalizing or internalizing trauma-related behavior. Students are either self-referred; referred by a teacher, administrator, or staff member; or identified by an ALIVE practitioner. Following the principle of immediate engagement based on emergent traumatic material, individual sessions are brief, lasting only 15 to 20 minutes. Using trauma-centered psychotherapy ( Johnson & Lubin, 2015 ), a brief inquiry addressing the current problem is conducted to identify the trauma trigger connected to the original harm, fostering cognitive discrimination. Conversation about the adverse experience proceeds in a calm, direct way focusing on differentiating between intrusive memories and the current situation at school ( Sajnani et al., 2014 ). Once the student exhibits greater emotional regulation, the ALIVE practitioner returns the student to the classroom in a timely manner and may provide either brief follow-up sessions for preventive purposes or, when appropriate, refer the student to more regular, clinical support in or out of the school.

Case Example 2

The following case example is representative of the brief, immediate, and open engagement with traumatic material and encouragement of cognitive discrimination. This intervention was conducted with a sixth grade student, Jacob (name and identifying information changed to ensure confidentiality), by an ALIVE practitioner (the second author).

I found Jacob in the hallway violently shaking a trash can, kicking the classroom door, and slamming his hands into the wall and locker. His teacher was standing at the door, distressed, stating, “Jacob, you need to calm down and go to the office, or I'm calling home!” Jacob yelled, “It's not fair, it was him, not me! I'm gonna fight him!” As I approached, I asked what was making him so angry, but he said, “I don't want to talk about it.” Rather than asking him to calm down or stop slamming objects, I instead approached the potential memory agitating him, stating, “My guess is that you are angry for a very good reason.” Upon this simple connection, he sighed and stopped kicking the trash can and slamming the wall. Jacob continued to demonstrate physical and emotional activation, pacing the hallway and making a fist; however, he was able to recount putting trash in the trash can when a peer pushed him from behind, causing him to yell. Jacob explained that his teacher heard him yelling and scolded him, making him more mad. Jacob stated, “She didn't even know what happened and she blamed me. I was trying to help her by taking out all of our breakfast trash. It's not fair.”

The ALIVE practitioner listens to students’ complaints with two ears, one for the current complaint and one for affect-laden details that may be connected to the original trauma to inquire further into the source of the trigger. Affect-laden details in case example 2 include Jacob's anger about being blamed (rather than toward the student who pushed him), his original intention to help, and his repetition of the phrase “it's not fair.” Having met with Jacob previously, I was aware that his mother suffers from physical and mental health difficulties. When his mother is not doing well, he (as the parentified child) typically takes care of the household, performing tasks like cooking, cleaning, and helping with his two younger siblings and older autistic brother. In the past, Jacob has discussed both idealizing his mother and holding internalized anger that he rarely expresses at home because he worries his anger will “make her sick.”

I know sometimes when you are trying to help mom, there are times she gets upset with you for not doing it exactly right, or when your brothers start something, she will blame you. What just happened sounds familiar—you were trying to help your teacher by taking out the garbage when another student pushed you, and then you were the one who got in trouble.

Jacob nodded his head and explained that he was simply trying to help.

I moved into a more detailed inquiry, to see if there was a more recent stressor I was unaware of. When I asked how his mother was doing this week, Jacob revealed that his mother's health had deteriorated and his aunt had temporarily moved in. Jacob told me that he had been yelled at by both his mother and his aunt that morning, when his younger brother was not ready for school. I asked, “I wonder if when the student pushed you it reminded you of getting into trouble because of something your little brother did this morning?” Jacob nodded. The displacement was clear: He had been reminded of this incident at school and was reacting with anger based on his family dynamic, and worries connected to his mother.

My guess is that you were a mix of both worried and angry by the time you got to school, with what's happening at home. You were trying to help with the garbage like you try to help mom when she isn't doing well, so when you got pushed it was like your brother being late, and then when you got blamed by your teacher it was like your mom and aunt yelling, and it all came flooding back in. The problem is, you let out those feelings here. Even though there are some similar things, it's not totally the same, right? Can you tell me what is different?

Jacob nodded and was able to explain that the other student was probably just playing and did not mean to get him into trouble, and that his teacher did not usually yell at him or make him worried. Highlighting this important differentiation, I replied, “Right—and fighting the student or yelling at the teacher isn't going to solve this, but more importantly, it isn't going to make your mom better or have your family go any easier on you either.” Jacob stated that he knew this was true.

I reassured Jacob that I could help him let out those feelings of worry and anger connected to home so they did not explode out at school and planned to meet again. Jacob confirmed that he was willing to do that. He was able to return to the classroom without incident, with the entire intervention lasting less than 15 minutes.

In case example 2, the practitioner was available for an immediate engagement with disturbing behaviors as they were happening by listening for similarities between the current incident and traumatic stressors; asking for specific details to more effectively help Jacob understand how he was being triggered in school; providing psychoeducation about how these two events had become confused and aiding him in cognitively differentiating between the two; and, last, offering to provide further support to reduce future incidents.

Germane to the practice of school social work is the ability to work flexibly within a public health model to attend to trauma within the school setting. First, we suggest that a primary implication for school social workers is not to wait for explicit problems related to known traumatic experiences to emerge before addressing trauma in the school, but, rather, to follow a model of prevention-assessment-intervention. School social workers are in a unique position within the school system to disseminate trauma-informed material to both students and staff in a preventive capacity. Facilitating this implementation will help to establish a tone and sharpened focus within the school community, norming the process of articulating and engaging with traumatic material. In the aforementioned classroom case example, we have provided a sample of how school social workers might work with entire classrooms on a preventive basis regarding trauma, rather than waiting for individual referrals.

Second, in addition to functional behavior assessments and behavior intervention plans, school social workers maintain a keen eye for qualitative behavioral assessment ( National Association of Social Workers, 2012 ). Using this skill set within a trauma-informed model will help to identify those students in need who may be reluctant or resistant to explicitly ask for help. As called for by Walkley and Cox (2013) , we suggest that using the information presented in Table 1 will help school social workers understand, identify, and assess the impact of trauma on early adolescent developmental tasks. If school social workers engage on a classroom level in trauma psychoeducation and conversations, the information in Table 3 may assist with assessment of children and provide a basis for checking in individually with students as warranted.

Third, school social workers are well positioned to provide individual targeted, trauma-informed interventions based on previous knowledge of individual trauma and through widespread assessment ( Walkley & Cox, 2013 ). The individual case example provides one way of immediately engaging with students who are demonstrating trauma-based behaviors. In this model, school social workers engage in a brief inquiry addressing the current trauma to identify the trauma trigger, discuss the adverse experience in a calm but direct way, and help to differentiate between intrusive memories and the current situation at school. For this latter component, the focus is on cognitive discrimination and emotional regulation so that students can reengage in the classroom within a short time frame.

Fourth, given social work's roots in collaboration and community work, school social workers are encouraged to use a systems-based approach in partnering with allied practitioners and institutions ( D'Agostino, 2013 ), thus supporting the public health tenet of establishing and maintaining a link to the wider community. This may include referring students to regular clinical support in or out of the school. Although the implementation of a trauma-informed program will vary across schools, we suggest that school social workers have the capacity to use a public health school intervention model to ecologically address the psychosocial and behavioral issues stemming from trauma exposure.

As increasing attention is being given to adverse childhood experiences, a tiered approach that uses a public health framework in the schools is necessitated. Nevertheless, there are some limitations to this approach. First, although the interventions outlined here are rooted in prevention and early intervention, there are times when formal, intensive treatment outside of the school setting is warranted. Second, the ALIVE program has primarily been implemented by ALIVE practitioners; the results from piloting this public health framework in other school settings with existing school personnel, such as school social workers, will be necessary before widespread replication.

The public health framework of prevention-assessment-intervention promotes continual engagement with middle school students’ chronic exposure to traumatic stress. There is a need to provide both broad-based and individualized support that seeks to comprehensively ameliorate the social, emotional, and cognitive consequences on early adolescent developmental milestones associated with traumatic experiences. We contend that school social workers are well positioned to address this critical public health issue through proactive and widespread psychoeducation and assessment in the schools, and we have provided case examples to demonstrate one model of doing this work within the school day. We hope that this article inspires future writing about how school social workers individually and systemically address trauma in the school system. In alignment with Walkley and Cox (2013) , we encourage others to highlight their practice in incorporating trauma-informed, school-based programming in an effort to increase awareness of effective interventions.

Card , N. A. , Stucky , B. D. , Sawalani , G. M. , & Little , T. D. ( 2008 ). Direct and indirect aggression during childhood and adolescence: A meta-analytic review of gender difference, intercorrelations, and relations to maladjustment . Child Development, 79 , 1185 – 1229 .

Google Scholar

Casey , B. J. , & Caudle , K. ( 2013 ). The teenage brain: Self control . Current Directions in Psychological Science, 22 ( 2 ), 82 – 87 .

Chafouleas , S. M. , Johnson , A. H. , Overstreet , S. , & Santos , N. M. ( 2016 ). Toward a blueprint for trauma-informed service delivery in schools . School Mental Health, 8 ( 1 ), 144 – 162 .

Chanmugam , A. , & Teasley , M. L. ( 2014 ). What should school social workers know about children exposed to intimate partner violence? [Editorial]. Children & Schools, 36 , 195 – 198 .

Cook , A. , Spinazzola , J. , Ford , J. , Lanktree , C. , Blaustein , M. , Cloitre , M. , et al.  . ( 2005 ). Complex trauma in children and adolescents . Psychiatric Annals, 35 , 390 – 398 .

D'Agostino , C. ( 2013 ). Collaboration as an essential social work skill [Resources for Practice] . Children & Schools, 35 , 248 – 251 .

Durlak , J. A. , Weissberg , R. P. , Dymnicki , A. B. , Taylor , R. D. , & Schellinger , K. B. ( 2011 ). The impact of enhancing students’ social and emotional learning: A meta-analysis of school-based universal interventions . Child Development, 82 , 405 – 432 .

Frydman , J. S. , & McLellan , L. ( 2014 ). Complex trauma and executive functioning: Envisioning a cognitive-based, trauma-informed approach to drama therapy. In N. Sajnani & D. R. Johnson (Eds.), Trauma-informed drama therapy: Transforming clinics, classrooms, and communities (pp. 179 – 205 ). Springfield, IL : Charles C Thomas .

Google Preview

Hartling , L. , & Sparks , J. ( 2008 ). Relational-cultural practice: Working in a nonrelational world . Women & Therapy, 31 , 165 – 188 .

Henderson , D. , & Thompson , C. ( 2010 ). Counseling children (8th ed.). Belmont, CA : Brooks-Cole .

Iachini , A. L. , Petiwala , A. F. , & DeHart , D. D. ( 2016 ). Examining adverse childhood experiences among students repeating the ninth grade: Implications for school dropout prevention . Children & Schools, 38 , 218 – 227 .

Jaycox , L. H. , Kataoka , S. H. , Stein , B. D. , Langley , A. K. , & Wong , M. ( 2012 ). Cognitive behavioral intervention for trauma in schools . Journal of Applied School Psychology, 28 , 239 – 255 .

Johnson , D. R. ( 2012 ). Ask every child: A public health initiative addressing child maltreatment [White paper]. Retrieved from http://www.traumainformedschools.org/publications.html

Johnson , D. R. , & Lubin , H. ( 2015 ). Principles and techniques of trauma-centered psychotherapy . Arlington, VA : American Psychiatric Publishing .

Moon , J. , Williford , A. , & Mendenhall , A. ( 2017 ). Educators’ perceptions of youth mental health: Implications for training and the promotion of mental health services in schools . Child and Youth Services Review, 73 , 384 – 391 .

Moradi , A. R. , Neshat Doost , H. T. , Taghavi , M. R. , Yule , W. , & Dalgleish , T. ( 1999 ). Everyday memory deficits in children and adolescents with PTSD: Performance on the Rivermead Behavioural Memory Test . Journal of Child Psychology and Psychiatry, 40 , 357 – 361 .

National Association of Social Workers . ( 2012 ). NASW standards for school social work services . Retrieved from http://www.naswdc.org/practice/standards/NASWSchoolSocialWorkStandards.pdf

Oehlberg , B. ( 2008 ). Why schools need to be trauma informed . Trauma and Loss: Research and Interventions, 8 ( 2 ), 1 – 4 .

Overstreet , S. , & Chafouleas , S. M. ( 2016 ). Trauma-informed schools: Introduction to the special issue . School Mental Health, 8 ( 1 ), 1 – 6 .

Overstreet , S. , & Matthews , T. ( 2011 ). Challenges associated with exposure to chronic trauma: Using a public health framework to foster resilient outcomes among youth . Psychology in the Schools, 48 , 738 – 754 .

Perfect , M. , Turley , M. , Carlson , J. S. , Yohannan , J. , & Gilles , M. S. ( 2016 ). School-related outcomes of traumatic event exposure and traumatic stress symptoms in students: A systematic review of research from 1990 to 2015 . School Mental Health, 8 ( 1 ), 7 – 43 .

Perry , D. L. , & Daniels , M. L. ( 2016 ). Implementing trauma-informed practices in the school setting: A pilot study . School Mental Health, 8 ( 1 ), 177 – 188 .

Porche , M. V. , Costello , D. M. , & Rosen-Reynoso , M. ( 2016 ). Adverse family experiences, child mental health, and educational outcomes for a national sample of students . School Mental Health, 8 ( 1 ), 44 – 60 .

Sajnani , N. , Jewers-Dailley , K. , Brillante , A. , Puglisi , J. , & Johnson , D. R. ( 2014 ). Animating Learning by Integrating and Validating Experience. In N. Sajnani & D. R. Johnson (Eds.), Trauma-informed drama therapy: Transforming clinics, classrooms, and communities (pp. 206 – 242 ). Springfield, IL : Charles C Thomas .

Saltzman , W. R. , Steinberg , A. M. , Layne , C. M. , Aisenberg , E. , & Pynoos , R. S. ( 2001 ). A developmental approach to school-based treatment of adolescents exposed to trauma and traumatic loss . Journal of Child and Adolescent Group Therapy, 11 ( 2–3 ), 43 – 56 .

Sibinga , E. M. , Webb , L. , Ghazarian , S. R. , & Ellen , J. M. ( 2016 ). School-based mindfulness instruction: An RCT . Pediatrics, 137 ( 1 ), e20152532 .

Tucker , C. , Smith-Adcock , S. , & Trepal , H. C. ( 2011 ). Relational-cultural theory for middle school counselors . Professional School Counseling, 14 , 310 – 316 .

Turner , H. A. , Shattuck , A. , Finkelhor , D. , & Hamby , S. ( 2017 ). Effects of poly-victimization on adolescent social support, self-concept, and psychological distress . Journal of Interpersonal Violence, 32 , 755 – 780 .

van der Kolk , B. A. ( 2005 ). Developmental trauma disorder: Toward a rational diagnosis for children with complex trauma histories . Psychiatric Annals, 35 , 401 – 408 .

Van Duijvenvoorde , A.C.K. , & Crone , E. A. ( 2013 ). The teenage brain: A neuroeconomic approach to adolescent decision making . Current Directions in Psychological Science, 22 ( 2 ), 114 – 120 .

Walkley , M. , & Cox , T. L. ( 2013 ). Building trauma-informed schools and communities [Trends & Resources] . Children & Schools, 35 , 123 – 126 .

Wigfield , A. W. , Lutz , S. L. , & Wagner , L. ( 2005 ). Early adolescents’ development across the middle school years: Implications for school counselors . Professional School Counseling, 9 ( 2 ), 112 – 119 .

Woodbridge , M. W. , Sumi , W. C. , Thornton , S. P. , Fabrikant , N. , Rouspil , K. M. , Langley , A. K. , & Kataoka , S. H. ( 2016 ). Screening for trauma in early adolescence: Findings from a diverse school district . School Mental Health, 8 ( 1 ), 89 – 105 .

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Trauma Case 1: Stab to Left Chest

Boston medical center – trauma case of the month, case #1: diagnostic laparoscopy in penetrating chest trauma.

by Rie Aihara, M.D. and Wayne LaMorte, M.D., Ph.D., M.P.H.

Pre-Hospital Data

A 17 year-old male from Michigan was visiting his cousins and friends in Boston, when he became a victim of a stabbing. This all began when the victim confronted an old friend about a personal conflict which occurred between them years ago. What started out as a verbal argument eventually resulted in physical violence. The victim sustained a single stab wound to the left chest in the mid axillary line, just below the level of the nipple. He was transported to our emergency department by Boston EMS. He was noted to be awake and alert throughout the entire transport.

Past Medical/Surgical History: Asthma Family History: Non-significant Medications: Inhalers as needed Allergy: No Known Drug Allergy (NKDA)

Trauma Room Assessment:

The patient was moved from the stretcher onto the examination table, and the only complaint obtained from the patient was shortness of breath.

Cardiac monitors, blood pressure-cuff and oxygen saturation probes were then placed on the patient.

Vital signs:

Heart rate- 90/min Blood Pressure- 130/70 Respiratory rate 25 Temperature- 97 F

Primary Survey:

Airway- patent airway as demonstrated by his ability to talk. Breathing- decreased breath sounds at the left base.

• Oxygen mask with 100% FiO2 was placed; & an oxygen saturation of 100% was obtained

Circulation – no active external bleeding Deficits – neurological exam grossly intact Exposure – the patient’s clothes were removed to throughly examine for other injuries Secondary survey: HEENT: no lacerations, no hematomas, no fractures palpated Neck: midline trachea, no JVD, no crepitus Chest: clear on right, single stab wound to the left chest in the mid-axillary line in the 4 th intercostal space, no crepitus, no bleeding, decreased breath sounds at the left base Cardiac: regular rate and rhythm (RRR), normal S1 and S2 Abdomen: present bowel sounds, soft, non-tender, non-distended Extremities: warm, present distal pulses Neuro: awake, GCS 15, no focal deficits

Radiological Survey:

Chest X-ray: left sided hemopneumothorax

• An upright CXR was obtained. We were able to sit the patient up because he had an isolated penetrating injury to the chest, and the mechanism of injury did not warrant spinal precautions. A pelvis and lateral C-spine films were also not obtained because of the isolated nature of the injury.

Other Pertinent Studies:

Transthoracic Echocardiogram: no pericardial effusion

• Because the weapon can be aimed at any direction (medially, superiorly, inferiorly), the heart can be potentially injured. A pericardial tamponade is lethal unless discovered and treated quickly.

Blood Work Ordered:

• Type and screen
• Coagulation panel
• Complete blood count (CBC)
• Arterial blood gas
• Toxicology screen

ER Procedures:

Chest tube placement: drained 300cc of frank blood

Change in status:

The patient at this time began complaining of a new subscapular pain, or pain between the shoulder blades. This was alarming to the trauma team for the following reasons.

• Patients with diaphragmatic injuries and irritation from the blood frequently exhibit referred pain in this distribution. If the knife wound had projected inferiorly penetrating the diaphragm, there was also a high likelihood of intraabdominal injuries. Therefore, it was decided that the patient required surgical exploration, and the patient was taken to the operating room.

Operating Room:

The surgical team performed a diagnostic laparoscopy in order to determine whether or not the diaphragm had been penetrated. The laparoscopy demonstrated an obvious defect in the diaphragm, as shown here.

Inspection within the abdomen demonstrated blood clots on the anterior surface of the stomach and the left lateral segment of the liver. In order to more carefully assess the extent of intra-abdominal injuries and carry out repair, the procedure was converted to an open laparotomy.

Upon exploration, there were three lacerations on the surface of the liver which required suture closure. There was also a 2 cm perforation of the anterior surface of the stomach which was closed primarily in two layers.

In order to assess the extent of intrathoracic injuries more closely, the laparoscope was advanced from the abdomen into the thorax through the diaphragmatic defect.

Examination of the pericardium showed no evidence of bleeding, contusion, or penetration.

We therefore proceeded to close the diaphragmatic perforation with interrupted Ethibond suture with pledgets.

Upon completion of the procedure the patient recovered without complications and was discharged to home in four days.

Major Teaching Points:

• Arterial blood gas is a better indicator of hemorrhage than hematocrit for the reasons described above.
• The peritoneal cavity can extend into the thoracic cavity as high as the 4th intercostal space. Any penetrating chest injury at or below that level has the potential to injure intra-abdominal organs.
• The presence of subscapular pain in a patient with a penetrating injury to the chest strongly suggests penetration of the diaphragm and a high risk of associated intra-abdominal injuries. This situation warrants surgical evaluation of the abdomen in the operating room.

Surgical exploration can be undertaken in one of two ways: a) the conventional approach is to perform an open laparotomy, and b) the alternate approach is to do a diagnostic laparoscopy. The primary purpose of the laparoscopy is to determine the presence of diaphragmatic perforation. If the diaphragm is intact, then there should be no intra-abdominal injuries. In this case, a midline incision can be avoided, and the recovery period will be shortened significantly. This can be beneficial to high risk patients such as those with pulmonary disease, cardiac disease and morbid obesity where a long midline incision can be a source of morbidity such as infection and respiratory compromise

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• Published: 16 June 2020

A patient with severe polytrauma with massive pulmonary contusion and hemorrhage successfully treated with multiple treatment modalities: a case report

• Futoshi Nagashima 1   na1 ,
• Satoshi Inoue 1   na1 &
• Miho Ohta 1  

Journal of Medical Case Reports volume  14 , Article number:  69 ( 2020 ) Cite this article

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The mortality rate is very high for patients with severe multiple trauma with massive pulmonary contusion containing intrapulmonary hemorrhage. Multiple treatment modalities are needed not only for a prevention of cardiac arrest and quick hemostasis against multiple injuries, but also for recovery of oxygenation to save the patient’s life.

Case presentation

A 48-year-old Japanese woman fell down stairs that had a height of approximately 4 m. An X-ray showed pneumothorax, pulmonary contusion in her right lung, and an unstable pelvic fracture. A chest drain was inserted and preperitoneal pelvic packing was performed to control bleeding, performing resuscitative endovascular balloon occlusion of the aorta. A computed tomography scan revealed massive lung contusion in the lower lobe of her right lung, pelvic fractures, and multiple fractures and hematoma in other areas. An emergency thoracotomy was performed, and then we performed wide wedge resection of the injured lung, clamping proximal to suture lines with two Satinsky blood vessel clamps. The vessel clamps were left in the right thoracic cavity. The other hemorrhagic areas were embolized by transcatheter arterial embolization. However, since her respiratory functions deteriorated in the intensive care unit, veno-venous extracorporeal membrane oxygenation was used for lung assist. Planned reoperation under veno-venous extracorporeal membrane oxygenation was performed on day 2. Since her respiratory condition improved gradually, the veno-venous extracorporeal membrane oxygenation circuit was withdrawn on day 7. She was transferred to the psychiatric ward of our hospital on day 75.

Utilizing multiple treatment modalities such as resuscitative endovascular balloon occlusion of the aorta, damage control surgery, transcatheter arterial embolization, and veno-venous extracorporeal membrane oxygenation with appropriate timing saves a patient with severe polytrauma with massive pulmonary contusion including intrapulmonary hemorrhage.

Peer Review reports

The mortality of multiple trauma with severe chest trauma of Abbreviated Injury Scale (AIS) > 3 is very high: 15.1% in all ages and 28.4% in those 65 years or older [ 1 ]. Quick hemostasis and treatments with appropriate prioritization for injured organs are essential to rescue patients with polytrauma, especially severe truncal trauma with pulmonary contusion with massive hemorrhage. Severe lung contusion can lead to massive hemothorax and severe tracheobronchial bleeding. Emergency surgery is determined based on the chest drainage volume in cases of hemothorax. However, it is relatively difficult to find tracheobronchial bleeding due to positive airway pressure ventilation at the early phase of injury. Massive amounts of tissue factor are released due to the lung contusion, which worsens coagulopathy and results in an increased amount of bleeding. Respiratory dysfunction can also be caused from blood flowing into the normal lung area from the pulmonary contusion area. In such cases, it is very difficult to maintain respiratory function with conventional respiratory management of a respirator only. Therefore, veno-venous extracorporeal membrane oxygenation (VV-ECMO) may be the best option, as well as the last resort, to save those patients’ lives.

Here we report a case of severe polytrauma of a 48-year-old woman with massive pulmonary contusion containing intrapulmonary hemorrhage; we were able to successfully save her life utilizing multiple treatment modalities, including resuscitative endovascular balloon occlusion of the aorta (REBOA), damage control surgery (DCS), transcatheter arterial embolization (TAE), intrabronchial block balloon, and VV-ECMO.

A 48-year-old Japanese woman fell down stairs that had a height of approximately 4 m. Her family called 119 (a direct-dial emergency number that connects the caller to the fire and emergency medical services) and the fire station simultaneously dispatched a “doctor-helicopter” from our hospital. She had past medical history including cholecystectomy and schizophrenia, and no remarkable family history. Her respiratory rate was 30 breaths/minute and blood oxygen saturation (SpO 2 ) was 90% with oxygen at 10 L/minute. Her breath sound in her right chest was diminished. Her pulse rate was 130 beats/minute and her blood pressure was 88/55 mmHg. Her extremities were cold with sweat present, suggesting she was in a shock status. A focused assessment sonography for trauma (FAST) revealed hemoperitoneum in the pelvic space and a hemothorax in the right side of her chest. Her consciousness levels were 12 points (E3, V4, M5) according to the Glasgow Coma Scale at first contact and no coarse paralysis of limbs was observed. She was brought to our hospital by a doctor-helicopter, undergoing initial fluid resuscitation and respiratory assist with a bag valve mask (BVM).

Her hemodynamics deteriorated remarkably with a pulse rate of 120 beats per minute and 50 mmHg systolic blood pressure on arrival. SpO 2 was below 90% under respiratory assist with BVM. She was given 6 units of type O Rh plus red blood cells (RBC). A 7-French aortic occlusion catheter (Rescue Balloon®, Tokai Medical Products, Aichi, Japan) was inserted from her right femoral artery and was inflated with 20 ml distilled water to maintain her systolic blood pressure above 90 mmHg. A chest X-ray showed pneumothorax and pulmonary contusion in her right lung (Fig.  1 a). A pelvis X-ray revealed an unstable fracture (Fig. 1 b). The FAST showed a moderate hemothorax in the right side of her chest and a small amount of hemoperitoneum in Morison’s pouch and Douglas pouch. A 28-French chest drain was inserted, and preperitoneal pelvic packing (PPP) was performed to control bleeding from the unstable pelvic fracture, followed by application of a pelvic binder. A whole-body contrast-enhanced computed tomography (CT) scan was performed. The chest CT scan revealed massive lung contusion with major active extravasation of contrast media in the lower lobe of her right lung and moderate lung contusion in the lower lobe of her left lung (Fig. 1 c). The abdominal CT revealed liver injuries with extravasation of contrast media, as well as massive hematoma in an erector spinae muscle with extravasation of contrast media and fractures of transverse process of lumbar vertebra (Fig. 1 d, e). The pelvic CT confirmed multiple pelvic fractures involving moderate hematoma with extravasation of contrast media in retroperitoneal pelvic space (Fig. 1 f).

X-ray and computed tomography findings on admission. a Chest X-ray showing heavy contusion and hemopneumothorax in the right lung. b Pelvis X-ray showed disruption of bilateral sacroiliac articulation and fractures of bilateral pubic bone. c A chest computed tomography scan revealed massive lung contusion with major active extravasation ( white arrow ) in the lower lobe of the right lung and moderate lung contusion in the lower lobe of the left lung. d Abdominal computed tomography scan revealed liver injuries with extravasation ( black arrow ). e , f Pelvic computed tomography showed massive hematoma with extravasation ( white arrow head ) in erector spinae muscle and fractures of transverse process of lumbar vertebrae ( e ) and multiple pelvic fractures involving moderate hematoma with extravasation of contrast media in retroperitoneal pelvic space ( f )

The laboratory data on initial arrival are shown in Table 1 . The Injury Severity Score (ISS) in this case was 48 and the probability of survival was calculated as 29.1%. We first decided to perform damage control thoracotomy since the right severe pulmonary contusion was thought to be a main bleeding source based on CT. Hemorrhage influx into the lumen of our patient’s trachea from the right pulmonary contusion was observed in a tracheal tube when she returned to the operation room (OR) in our emergency department (ED) from the CT room. A double lumen tracheal tube was replaced with a single lumen tracheal tube to prevent blood influx into healthy lung areas before emergency thoracotomy in a supine position. The amount of bleeding in the right thoracic cavity was approximately 1500 ml. The main sources of bleeding in her chest were the lung contusion area of the lower lobe of her right lung and multiple rib fractures. Intrathoracic packing with surgical gauze was performed as a temporary hemostasis to control bleeding from the sites of fractures of ribs. Since the right lung contusion had extended to near the hilum of lung (Fig.  2 a), the hilum of lung was clamped for temporary hemostasis of the lung. At that time, her body temperature was 35.2 °C, base excess and pH of arterial blood gas analysis (BGA) were 10.5 mmol/L and 7.099, respectively, and a persistent oozing of blood from a non-surgical site was recognized. Therefore, we decided to perform wide wedge resection of the lung using a surgical stapling device as a DCS instead of an anatomical lobectomy. We converted the hilum clamp to a limited clamp to the injured lobe with two Satinsky blood vessel clamps. The vessel clamps were left in the right thoracic cavity, clamping proximal to suture lines. Then, therapeutic intrathoracic packing for hemorrhage from multiple rib fractures was performed. Surgical packing gauzes were mainly put in the dorsal and lower side in right thoracic cavity in order to maintain respiratory function of the upper and middle lobes of her right lung, and the vessel clamps were stabilized with additional surgical towels. After the placement of a chest drain, a temporary vacuum packing chest closure was performed and DCS was finished (total surgical time was 55 minutes).

The findings during damage control thoracotomy and views of the surgical site and operation room just before planned reoperation. a The lower lobe of right lung is remarkably swollen due to intrapulmonary hemorrhage and hematoma ( white arrow head ). b The removed lower lobe of right lung is shown ( white arrow head ). c Two vascular clamps were placed at the proximal site of the resected area to avoid unexpected rebleeding. d Pulmonary function was well maintained by veno-venous extracorporeal membrane oxygenation during the surgery

After the DCS for the chest, TAE was performed for severe liver injuries including medial segment and right lobe with gelatin sponge. Furthermore, her left subcostal artery, left first and fourth lumbar arteries, right first to fourth lumbar arteries, right superior gluteal artery, bilateral iliolumbar arteries, right obturator artery, and left lateral sacral artery were embolized in the same fashion (total procedure time was 118 minutes). Meanwhile, her respiratory status worsened including decreased partial pressure of oxygen in arterial blood (PaO 2 )/fraction of inspired oxygen (FiO 2 ) (P/F) ratio and elevation of partial pressure of carbon dioxide (pCO 2 ) on arterial blood gas. In the intensive care unit (ICU), her respiratory functions deteriorated with a P/F ratio below 50: pCO 2 on BGA over 70 mmHg, pH of 7.099, and base deficit of − 12 mmol/L. Since a ventilator was no longer sufficient to maintain her respiratory condition, VV-ECMO was initiated as a lung assist: FiO 2 1.0, oxygen flow 2.0 L/minute, and veno-venous (VV) blood flow 4.5〜5.0 L/minute (Fig.  3 b). A bronchial block balloon was inserted into her right lower bronchus to reduce pressure to the suture lines of the lung. Blood and clots in the other side of the trachea and bronchus were toileted with a bronchoscope. Her hemodynamics and respiratory function improved gradually with these treatments. A blood transfusion continued to maintain the following: hemoglobin (Hb) > 9.0 g/dl, fibrinogen > 150 mg/dl, and platelet > 10 × 10 4 /μl. The total blood transfusion for 24 hours included 82 units of RBC, 136 units of fresh frozen plasma (FFP), and 70 units of platelet concentrate (PC).

Chest X-ray findings post operation. a Chest X-ray findings following damage control surgery (thoracotomy). The bleeding source was clamped ( black arrowhead ) and intrathoracic packing was performed. b Chest X-ray findings post establishment of veno-venous extracorporeal membrane oxygenation system. The catheter to establish the veno-venous extracorporeal membrane oxygenation was placed from the right internal jugular vein (feeding catheter, white arrow ) and right femoral vein (drainage catheter, black arrow ). c Chest X-ray findings after planned reoperation on day 2. d Chest X-ray findings on day 15 showed a significant improvement in both lung areas

The planned reoperation for her chest and pelvis under VV-ECMO was performed on day 2 (Fig. 2 c, d). When Satinsky blood vessel clamps were cautiously removed, there was a slight oozing of blood from the suture line at the resection site of the lower lobe of her right lung. The vessel forceps were reclamped and the stump was interruptedly sutured with two pairs of Teflon pledgets for hemostasis. We closed her chest with two chest drains placed following additional suture for hemorrhage from the multiple rib fractures area (Fig. 3 c). Since slight bleeding continued from the right side of her pelvic retroperitoneal space after removal of PPP gauze, repacking and external fixation for pelvic fracture were also performed. On day 3, RBC and PC were appropriately transfused as our patient’s Hb and platelets were decreased due to VV-ECMO. Her respiratory function was completely dependent on VV-ECMO. Fluid infusion was restricted and a diuretic was administered to make her run on the dry side and her bloody and mucinous phlegm was deliberately removed by a bronchoscope. On day 5, the PPP gauze was removed and the wound was definitively closed. Her respiratory condition improved gradually, and P/F ratio became over 250, and her pCO 2 level was within the normal limit when FiO 2 and blood flow of VV-ECMO were decreased. The VV-ECMO circuit was withdrawn and the bronchial block balloon was removed on day 7. Our patient’s clinical course with intervention and examination and the change in lactate levels and P/F ratio until day 8 are shown in Fig.  4 . On day 15, her respiratory condition was improved to the desired extent with no need for a ventilator (Fig. 3 d). Pneumonia and right intrathoracic infection subsequently occurred and were treated by antibiotics. She needed another 45 days of rehabilitation to be able to walk independently, and was transferred to the psychiatric ward of our hospital on day 75.

Clinical course and treatment. Elapsed course of intervention and examination were shown with a value of lactate and partial pressure of oxygen in arterial blood/fraction of inspired oxygen ratio. On day 1, preperitoneal pelvic packing was performed introducing resuscitative endovascular balloon occlusion of the aorta as hemostatic treatment strategy. Emergency thoracotomy after computed tomography examination was performed, and transcatheter arterial embolization was sequentially performed to stop the bleeds from multiple injuries. Veno-venous extracorporeal membrane oxygenation was performed because of a deterioration of the patient’s pulmonary function with a partial pressure of oxygen in arterial blood/fraction of inspired oxygen ratio of below 50 just after admission to the intensive care unit. The partial pressure of oxygen in arterial blood/fraction of inspired oxygen ratio was remarkably improved by veno-venous extracorporeal membrane oxygenation, and the patient was successfully weaned off from the veno-venous extracorporeal membrane oxygenation on day 7. There was an obvious inverse correlation between lactate level and partial pressure of oxygen in arterial blood/fraction of inspired oxygen ratio. The lactate value was affected by hypoxia as well as hemorrhagic shock. On day 2, the planned reoperations for the chest and pelvis were performed and the hemorrhages in the thoracic injuries were successfully stopped. Since bleeding from the pelvic fracture could not be fully controlled, preperitoneal pelvic repacking was performed, and packing gauze was removed on day 5. A bronchial block balloon was inserted into the right lower bronchus to protect the stump of lung resection site from collapse due to excess intrabronchial pressure. We performed tracheostomy on day 5 as the patient was required to be on mechanical ventilation for a long period of time. CT computed tomography, DCS damage control surgery, ICU intensive care unit, IVR interventional radiology, P / F partial pressure of oxygen in arterial blood/fraction of inspired oxygen, PPDP preperitoneal pelvic depacking, PPP preperitoneal pelvic packing, PPRP preperitoneal pelvic repacking, REBOA resuscitative endovascular balloon occlusion of the aorta, VV - ECMO veno-venous extracorporeal membrane oxygenation

The present case was on the verge of cardiac and respiratory arrest due to a serious polytrauma with severe hemorrhagic shock, which required a rapid control of bleeding using a damage control strategy and respiratory management utilizing VV-ECMO.

We determined to control the massive bleeding with REBOA according to FAST and X-ray findings, and control the shock caused by severe hemorrhage. In this case, time from admission to successful temporary aortic occlusion (TAO) with REBOA was only 12 minutes. In the American Association for the Surgery of Trauma (AAST) prospective Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery (AORTA) registry, TAO was not significantly different in the time between an open aortic occlusion (OAO) and REBOA: median/interquartile range (IQR) of 15.0/70 and 30.5/36 minutes, respectively [ 2 ]. Our TAO with REBOA was very short and was performed as quickly as the time it took for OAO. REBOA was placed appropriately and smoothly by experienced trauma surgeons as almost all the things needed for REBOA insertion were well prepared in advance. All required preparations for REBOA, including equipment, staffing, place (OR), and activation of the DCS were ordered from the accident scene by a doctor-helicopter staff member. Utilizing REBOA in combination with PPP is a very powerful strategy to achieve hemostasis for both the artery and vein in patients with severe unstable pelvic fracture, especially when they are performed quickly and timely.

A CT scan revealed the severe pulmonary contusion with massive intrapulmonary hematoma, which probably required surgery, and multiple injuries with extravasations of contrast media on liver, spine, and pelvis, which required TAE. We determined to perform surgery on her chest first because the pulmonary contusion had a great risk of severe intrathoracic and tracheal bleeding, which would lead to severe coagulopathy due to the release of a multitude of tissue factors and subsequent pulmonary failure. We observed a lung laceration reaching to near the pulmonary hilum, as well as other multiple injuries such as the thoracic wall and sites of fractures of ribs that were causing continuous bleeding on the operation. We decided to perform wide wedge resection of the injured lung as a DCS. It is reported that damage control thoracic surgery is suitable for patients with severe chest trauma with physiological derangement [ 3 ]. Mortality was increased in an extent-dependent manner for lung resection: pneumonectomy at 62%, lobectomy at 35%, and wedge resection at 22% [ 4 ]. Wedge resection can be performed with a simple and quick procedure and is often applied as a DCS. However, wide wedge resection of the injured lung which reaches near hilum of lung, such as in the present case, is a risky procedure. If large blood vessels and bronchus exist in the excision site, a surgical automatic suturing device occasionally cannot seal them completely, which may result in major bleeding and large air leak with traumatic coagulopathy. Furthermore, repair of such bleeding and air leakage from the suture line may be very difficult, because the resection site tends to move into the inner part of the mediastinum. Therefore, we determined to leave the vessel forceps clamped proximal to suture lines in the intrathoracic space until the planned reoperation was performed. The vessel clamps were secured by putting gauze around them so they did not move from their original positions. Packing gauze was also applied to control minor venous bleeding and oozing from multiple sites of fractures of ribs. The chest was temporarily closed by vacuum packing system. Although it has been reported that intrathoracic packing is an effective method of hemostasis for severe chest trauma as a DCS [ 5 , 6 ], it may also cause respiratory dysfunction and hemodynamic instability. Interestingly, it has been previously demonstrated that the peak airway pressure in vacuum packing closure (VPC) using intrathoracic packing group was lower than that in the definitive thoracic closure group in studies of chest closure of patients who underwent emergent thoracotomy [ 3 , 7 , 8 ]. We found that intrathoracic packing with temporary closure using VPC was very effective in a case of polytrauma which required control of bleeds from multiple sites simultaneously.

In the present case, VV-ECMO was applied for her severe respiratory failure refractory to conventional ventilator support, which was progressed after DCS and TAE. There are some reports regarding application and usage of VV-ECMO in trauma cases [ 9 ]. Previous studies demonstrated that survival rate was improved by VV-ECMO when utilized for patients with lung trauma with no signs of improvement of hypoxia and hypercapnia on conventional ventilator [ 9 , 10 ]. The mean time from injury to initiation of VV-ECMO was 3.2 days (9) and 4.6 days (10) in these reports, whereas time in our case was approximately 8 hours. In these reports, VV-ECMO was performed for trauma-induced acute respiratory distress syndrome (ARDS) that occurred a few days after the injury. It is known that early application of VV-ECMO for patients with severe trauma is highly challenging when bleeding is not fully controlled since an insufficient fluid volume in the patient’s circulation leads to possible VV-ECMO circuit failure, including blood drainage or infusion failure. However, appropriate hemostasis and blood transfusion were performed in our case, and thus VV-ECMO worked perfectly without any specific troubles, and it could also be initiated in the early stage after the injury.

Utilizing multiple treatment modalities such as REBOA, DCS, TAE, intrabronchial block balloon, and VV-ECMO with appropriate timing saves a patient with severe polytrauma with massive pulmonary contusion including intrapulmonary hemorrhage.

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Abbreviations

American Association for the Surgery of Trauma

Resuscitative endovascular balloon occlusion of the aorta

• Damage control surgery

Transcatheter arterial embolization

Veno-venous

Veno-venous extracorporeal membrane oxygenation

Intensive care unit

Interquartile range

Abbreviated Injury Scale

Focused assessment sonography for trauma

Fraction of inspired oxygen

Bag valve mask

Partial pressure of carbon dioxide

Preperitoneal pelvic packing

Red blood cells

Blood oxygen saturation

Computed tomography

Injury Severity Score

Operation room

Emergency department

Blood gas analysis

Partial pressure of oxygen in arterial blood (PaO 2 )/fraction of inspired oxygen (FiO 2 )

Fresh frozen plasma

Platelet concentrate

Temporary aortic occlusion

Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery

Open aortic occlusion

Vacuum packing closure

Acute respiratory distress syndrome

Pape HC, Zelle B, Lohse R, Stalp M, Hildebrand F, Krettek C, Panzica M, Duhme V, Sittaro NA. Evaluation and outcome of patients after polytrauma--can patients be recruited for long-term follow-up? Injury. 2006;37(12):1197–203.

Article   Google Scholar  

DuBose JJ, Scalea TM, Brenner M, Skiada D, Inaba K, Cannon J, Moore L, Holcomb J, Turay D, Arbabi CN, et al. The AAST prospective Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery (AORTA) registry: Data on contemporary utilization and outcomes of aortic occlusion and resuscitative balloon occlusion of the aorta (REBOA). J Trauma Acute Care Surg. 2016;81(3):409–19.

O'Connor JV, DuBose JJ, Scalea TM. Damage-control thoracic surgery: Management and outcomes. J Trauma Acute Care Surg. 2014;77(5):660–5.

Martin MJ, McDonald JM, Mullenix PS, Steele SR, Demetriades D. Operative management and outcomes of traumatic lung resection. J Am Coll Surg. 2006;203(3):336–44.

Caceres M, Buechter KJ, Tillou A, Shih JA, Liu D, Steeb G. Thoracic packing for uncontrolled bleeding in penetrating thoracic injuries. South Med J. 2004;97(7):637–41.

Vargo DJ, Battistella FD. Abbreviated thoracotomy and temporary chest closure: an application of damage control after thoracic trauma. Arch Surg. 2001;136(1):21–4.

Article   CAS   Google Scholar  

Lang JL, Gonzalez RP, Aldy KN, Carroll EA, Eastman AL, White CQ, Funk GA, Phelan HA. Does temporary chest wall closure with or without chest packing improve survival for trauma patients in shock after emergent thoracotomy? J Trauma. 2011;70(3):705–9.

O'Connor J, Kells A, Henry S, Scalea T. Vacuum-assisted closure for the treatment of complex chest wounds. Ann Thorac Surg. 2005;79(4):1196–200.

Guirand DM, Okoye OT, Schmidt BS, Mansfield NJ, Aden JK, Martin RS, Cestero RF, Hines MH, Pranikoff T, Inaba K, et al. Venovenous extracorporeal life support improves survival in adult trauma patients with acute hypoxemic respiratory failure: a multicenter retrospective cohort study. J Trauma Acute Care Surg. 2014;76(5):1275–81.

Ried M, Bein T, Philipp A, Muller T, Graf B, Schmid C, Zonies D, Diez C, Hofmann HS. Extracorporeal lung support in trauma patients with severe chest injury and acute lung failure: a 10-year institutional experience. Crit Care. 2013;17(3):R110.

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Acknowledgements

We would like to acknowledge the patient and the patient’s family for allowing the case to be published.

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Futoshi Nagashima and Satoshi Inoue contributed equally to this work.

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Department of Trauma Surgery and Surgical Critical Care, Saga University, Faculty of Medicine, 5-1-1 Nabeshima, Saga, 849-8501, Japan

Futoshi Nagashima, Satoshi Inoue & Miho Ohta

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FN and SI contributed equally to write this manuscript. All authors contributed to the diagnosis, the treatment including the surgery, and the intensive care and the clinical management of the patient. All authors read and approved the final manuscript.

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Correspondence to Futoshi Nagashima .

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Nagashima, F., Inoue, S. & Ohta, M. A patient with severe polytrauma with massive pulmonary contusion and hemorrhage successfully treated with multiple treatment modalities: a case report. J Med Case Reports 14 , 69 (2020). https://doi.org/10.1186/s13256-020-02406-9

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Received : 10 September 2019

Accepted : 22 May 2020

Published : 16 June 2020

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Exploring the impact of trauma type and extent of exposure on posttraumatic alterations in 5-HT1A expression

• Michael W. Lewis   ORCID: orcid.org/0000-0002-3903-9055 1 ,
• Russell T. Jones 1   na1 &
• Margaret T. Davis   ORCID: orcid.org/0000-0001-7297-710X 2   na1  

Translational Psychiatry volume  10 , Article number:  237 ( 2020 ) Cite this article

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• Molecular neuroscience
• Pathogenesis

The long-term behavioral, psychological, and neurobiological effects of exposure to potentially traumatic events vary within the human population. Studies conducted on trauma-exposed human subjects suggest that differences in trauma type and extent of exposure combine to affect development, maintenance, and treatment of a variety of psychiatric syndromes. The serotonin 1-A receptor (5-HT1A) is an inhibitory G protein-coupled serotonin receptor encoded by the HTR1A gene that plays a role in regulating serotonin release, physiological stress responding, and emotional behavior. Studies from the preclinical and human literature suggest that dysfunctional expression of 5-HT1A is associated with a multitude of psychiatric symptoms commonly seen in trauma-exposed individuals. Here, we synthesize the literature, including numerous preclinical studies, examining differences in alterations in 5-HT1A expression following trauma exposure. Collectively, these findings suggest that the impact of trauma exposure on 5-HT1A expression is dependent, in part, on trauma type and extent of exposure. Furthermore, preclinical and human studies suggest that this observation likely applies to additional molecular targets and may help explain variation in trauma-induced changes in behavior and treatment responsivity. In order to understand the neurobiological impact of trauma, including the impact on 5-HT1A expression, it is crucial to consider both trauma type and extent of exposure.

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Introduction

Exposure to potentially traumatic events is common, with an estimated rate of over 80% in the United States and 70% worldwide 1 . However, long-term behavioral, psychological, and neurobiological effects of exposure vary considerably 2 . Some individuals experience rapid and sustained natural recovery, while others develop chronic trauma-related psychopathology 3 . Importantly, the nature and extent of trauma exposure combine to produce different outcomes; research suggests that exposure to qualitatively different events and different degrees of exposure lead to different psychiatric and neurobiological outcomes 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 . For example, qualitatively different events (e.g., rape, assault, and natural disaster) are associated with different levels of conditional risk for posttraumatic stress disorder (PTSD; 19% rape and 0.3% natural disaster) 20 . Similarly, different trauma types are differentially correlated with the emergence of several other psychiatric diagnoses and sequalae following trauma exposure (e.g., depression, anxiety, substance abuse, conduct problems, eating disorders, suicidal ideation, and psychosis) 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 . Furthermore, research suggests that genetic risk for PTSD covaries with trauma type, timing, severity, and degree of exposure 22 , 23 , 24 , 25 , 26 , 27 , 28 . Critically, research suggests that the dissociative subtype of PTSD and informally recognized subtypes of major depressive disorder (MDD; e.g., anxious depression, and psychotic subtype) may develop as a result of childhood trauma history, are characterized by distinct neurobiological mechanisms, and require different treatment approaches 29 , 30 , 31 , 32 , 33 , 34 . This suggests that common neurobiological factors among trauma-exposed individuals may contribute to heterogeneity in psychiatric symptoms and treatment responsivity; neurobiological phenotypes of trauma-induced psychiatric dysfunction transcend traditional diagnostic categories. In order to understand observed variability in the long-term effects of trauma exposure, it may be necessary to examine the relationship between variability in the nature and extent of trauma exposure and associated trauma-induced neurobiological alterations.

Research suggests that individual differences in the expression and activity of serotonin 1-A receptor (5-HT1A) are associated with a multitude of psychiatric symptoms commonly seen in trauma-exposed individuals 35 , 36 , 37 , 38 , 39 , 40 . Previous reviews have synthesized literature related to the role of 5-HT1A in depression, anxiety, memory, fear learning, impulsivity, suicide, and social dysfunction 35 , 36 , 37 , 38 , 39 , 40 . In addition, a multitude of preclinical studies have examined trauma-induced alterations in 5-HT1A 41 . Though the preclinical literature is consistent in suggesting that trauma alters 5-HT1A expression, specific findings diverge; some studies have observed increasing expression 41 , while others have observed the opposite 42 . In addition, many studies have presented conflicting evidence regarding specific brain regions in which increases and decreases occur 41 , 42 , 43 . Here, we synthesize the literature, including numerous preclinical studies, examining differences in alterations in 5-HT1A expression following trauma exposure. We suggest that observed inconsistencies may be accounted for in part by the influence of differences in the type of trauma subjects are exposed to. Furthermore, we suggest that the same is likely true of other molecular targets and that consideration of trauma type is a key aspect of accurate data interpretation. Thus, we examine the literature on 5-HT1A as an exemplar of a more general observation: in order to understand the neurobiology of trauma, one must account for covariance of trauma type and neurobiological alterations.

The 5-HT1A receptor is one of seven inhibitory G protein-coupled serotonin receptors and is encoded by the HTR1A gene 44 . It is found in high density in areas associated with serotonin release (raphe nuclei), memory (hippocampus), fear (amygdala), pleasure (septum), and higher-order cognition (cerebral cortex) 38 , 45 , 46 , 47 , 48 , 49 , 50 , 51 . Physiologically, 5-HT1A activity in areas of high density as well as in several areas of lower density regulates neurotransmitter (e.g., dopamine, acetylcholine, noradrenaline, GABA, and glutamate) and hormone (e.g., cortisol and oxytocin) release as well as neural activity and functional connectivity 52 , 53 , 54 , 55 , 56 , 57 , 58 . In addition, 5-HT1A activity has been shown to modulate a wide array of adaptive and maladaptive behaviors. For example, in rodents, the 5-HT1A agonist 8-OH-DPAT has been found to increase impulsive action at low doses, and decrease impulsive action at higher doses 59 . Moreover, both agonists and antagonists of 5-HT1A have been shown to have antidepressant effects in preclinical models 60 , 61 . The region-specific nature of the physiological effects of 5-HT1A may be relevant to its impact on adaptive and maladaptive behaviors.

Among trauma-exposed individuals, numerous human studies have identified social behaviors as key differentiating factors which separate resilience from vulnerability (e.g., Refs. 62 , 63 ). Though it is generally accepted that 5-HT1A exerts strong effects on social behavior, those effects are highly complex 64 , 65 . For example, one study found that the 5-HT1A full agonist 8-OH-DPAT, the 5-HT1A partial agonist ipsapirone, and the region-specific partial agonist of 5-HT1A autoreceptors/antagonist of 5-HT1A heteroreceptors MDL-73,005-EF each led to a distinct pattern of effects on social behavior in rodents 64 . Regarding the overall frequency of pro-social behavior, 8-OH-DPAT led to an increase, MDL-73,005-EF led to a decrease, and ipsapirone had no effect 64 . In addition to the overall effects, each of the three drugs led to a specific combination of increases and decreases in each of six specific pro-social behaviors, six specific aggressive behaviors, and five specific defensive behaviors 64 . In addition, one study found that treating female marmoset monkeys with the 5-HT1A agonist 8-OH-DPAT impaired pair bond quality and decreased female sexual behavior 66 . By contrast, flibanserin, a regionally selective postsynaptic 5-HT1A heteroreceptors agonist/5-HT2A antagonist, improved pair bond quality and increased female sexual behavior 66 . Studies such as these have demonstrated the ability of different types of alterations in 5-HT1A activity (as well as its interactions with other receptors) to affect behaviors (both adaptive and maladaptive) shown to develop in the wake of trauma exposure.

In addition to social functioning, 5-HT1A modulates numerous trauma-relevant behaviors. A multitude of preclinical and human studies have linked 5-HT1A expression and activation to a number of well-known trauma sequalae; examples include depression (for reviews, see Refs. 35 , 44 , 67 , 68 ), anxiety (for reviews, see Refs. 36 , 68 ), memory (for reviews, see Refs. 38 , 69 , 70 , 71 ), fear learning (for review, see Ref. 37 ), impulsivity (for review, see Ref. 39 ), suicide (for review, see Ref. 40 ), substance abuse (e.g., Ref. 72 ), social dysfunction (for review, see Ref. 64 ), and pharmacological treatment responsivity (for reviews, see Refs. 73 , 74 ). Given the variety of trauma-related behaviors and neurobiological substrates that 5-HT1A receptors modulate, it is reasonable to hypothesize that heterogeneity in trauma-induced 5-HT1A alterations contributes to heterogeneity in psychiatric symptom expression. However, while numerous reviews discuss the impact of 5-HT1A on behaviors which are implicated in trauma, no works of which we are aware have synthesized the literature regarding trauma’s impact on 5-HT1A.

We argue that the importance of synthesizing the literature regarding the relationship between trauma exposure and 5-HT1A expression is that 5-HT1A can act as an exemplar of a general principle: that trauma type, chronicity, and duration likely have an impact on many (and possibly all) trauma-induced molecular alterations. Many of the fundamental mechanisms through which stress alters gene expression in general (e.g., transcription factors, miRNA, etc.) and 5-HT1A expression specifically (e.g., Freud-1 and miR-135a) regulate the expression of multiple genes rather than just one particular gene 44 . Thus, it is unlikely that different types of trauma or degrees of exposure would differentially impact the expression of one gene but not others. Though any number of molecular targets could theoretically be used to demonstrate this principle, 5-HT1A was used in this article for both practical and theory-driven reasons.

Our justification for selecting 5-HT1A as an exemplar here is twofold. First, because 5-HT1A is among the most widely studied molecular mechanisms of stressor-related psychopathology, a robust 5-HT1A focused preclinical literature exists 44 . This is critical because examination of the importance of trauma type and extent of exposure requires comparison of studies for which all other methodologies overlap; only a small portion of the literature meets all of those criteria. Second, by focusing on a molecular target that is widely studied in relation to stressor-related disorders but not often studied in relation to trauma, this work aims to call attention to a possible gap in the literature. In addition to PTSD, we believe that this work has the potential to inform the literature on depression, anxiety, and many other psychiatric diagnoses linked with 5-HT1A dysfunction.

5-HT1A and trauma: human studies

To date, very few published studies have directly examined the association between trauma exposure and 5-HT1A expression in humans. In addition, none have accounted for trauma type. However, a recent positron emission tomography (PET) study observed a negative correlation between chronic psychosocial stress and 5-HT1A availability in vivo in the hippocampus, anterior cingulate cortex, and insular cortex in humans 75 . Furthermore, using PET, subjects with PTSD have been found to have elevated 5-HT1A availability across 13 brain regions 76 . Notably, the results of some PET studies have been shown to vary as a function of which outcome measure researchers employ. For example, when researchers examining the relationship between PTSD and 5-HT1A availability used binding potential nondisplaceable uptake (BP ND ; the outcome measure employed in the psychosocial stress study) rather than binding potential free plasma concentration (BP F ), no relationship between PTSD and 5-HT1A was observed 76 , 77 . Another issue that limits interpretation of these findings is the cross-sectional nature of the study designs. Without longitudinal data it is not possible to determine whether dysregulated 5-HT1A expression occurred as a result of stress exposure (traumatic or otherwise) or represents a preexisting risk factor for stressor-induced disorders. For example, elevated 5-HT1A availability has been observed in subjects with remitted MDD and has been found to be a heritable preexisting risk factor for MDD 78 , 79 . While no published human studies have used longitudinal designs to study the effect of trauma on 5-HT1A expression, a body of preclinical literature suggests that trauma exposure may alter 5-HT1A expression.

Preclinical models of traumatic stress exposure

In both humans and rodents, the line between non-trauma stress exposure and traumatic stress exposure is often blurry and imprecisely defined. In fact, the “Diagnostic and Statistical Manual” (DSM) definition of trauma exposure has been altered multiple times 80 . Though each DSM has presented a binary definition of PTE exposure, it is unclear whether the present dichotomous approach is adequate 80 . As mentioned previously, qualitatively different types of traumas can produce distinct neurobiological and behavioral consequences (e.g., Ref. 21 ). In addition, while the DSM uses a binary approach to define the boundary between “stress” and “trauma,” it may be important to focus more on qualitative aspects of distinct types of intense stressors and less on a dichotomous variable. For example, both criterion-A-type and noncriterion-A-type childhood maltreatment have been found to be negatively correlated with fractional anisotropy in the inferior longitudinal fasciculus 81 . Controversies regarding the use of a binary definition of trauma, which may incorrectly exclude some extreme stressors while incorrectly amalgamating others, have led to calls for a more fine-grained approach 80 .

The ambiguous and heterogeneous nature of PTEs is reflected in the preclinical trauma literature. A number of different preclinical models have been used to study trauma, including single prolonged stress (SPS), predator threat, restraint stress (RS; aka immobilization stress), inescapable electric shock (IES), fear conditioning (FC), chronic unpredictable stress (CUS; aka chronic variable stress), chronic social defeat (CSD), maternal separation (MS), and MS unpredictable stress. These paradigms and their relationship with trauma have been described and reviewed elsewhere (e.g., Refs. 53 , 82 , 83 , 84 , 85 ). Of note, CUS is an umbrella term encompassing any paradigm which involves daily exposure to one or more different stressors in a randomized sequence for 1 week or longer 86 . In this work, we only include CUS paradigms that include exposure to at least one of the aforementioned acute traumatic stressors. Just as many of the DSM-defined criterion A traumas were not included in the original definition of trauma exposure 80 , most of these preclinical trauma models were not initially conceptualized as representing trauma (e.g., RS, IES, FC, CUS, CSD, and MS) 82 , 83 . Due to the multifaceted and heterogeneous nature of potentially traumatic events, previous reviews have stated that no single preclinical model of trauma can adequately capture all aspects of trauma and that an ideal approach should draw from a variety of distinct models 82 , 83 .

While not traditionally viewed as a trauma paradigm, forced swim (FS) has been described as an uncontrollable and anxiogenic life-threatening situation 87 and has been used in several studies to model trauma-related abnormalities in neurobiology, memory, and pain 88 , 89 , 90 . The behavioral effects of both acute and chronic FS stress have been measured using a number of additional preclinical tests (e.g., sucrose preference test, tail suspension test, elevated plus maze, open field test, social exploration test, Morris water maze, object location test, prepulse inhibition, cocaine preference, ethanol preference) (e.g., Refs. 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 ). Based on those tests, numerous studies have found evidence that FS can induce preclinical dysfunctions reflective of trauma sequalae including anhedonia (e.g., Ref. 92 ), anxiety (e.g., Ref. 110 ), social anxiety (e.g., Ref. 100 ), cognitive dysfunction (e.g., Ref. 108 ), depression (e.g., Ref. 93 ), and substance abuse (e.g., Ref. 109 ). Based on the intense nature of the stressor and its capacity for causing behavioral dysfunctions reflective of multiple facets of trauma-induced psychopathology, FS may represent an additional model of potentially traumatic event exposure. Thus, in order to provide a comprehensive picture of covariance of trauma type and 5-HT1A alterations, FS is included in this review.

Importantly, preclinical trauma models vary qualitatively in ways that make them appropriate analogs of different types of traumatic event exposure. In humans, interpersonal traumas (e.g., physical assault, sexual assault, and family violence) are qualitatively different from non-interpersonal traumas (e.g., severe accident, natural disaster, and life-threatening illness); this contributes to differences in psychiatric symptom severity and outcomes 111 , 112 . Similarly, some preclinical models incorporate a clear social component (e.g., CSD and MS), while others lack a social component (e.g., FC and RS) 83 . Additional clinically relevant qualitative factors which vary among preclinical trauma models include degree of threat of bodily harm, actual physical pain inflicted, and predictability 83 . In addition to qualitative differences, preclinical trauma models can vary in duration (time per exposure) and chronicity (days of exposure) 83 . In humans, increases in both duration and chronicity of trauma exposure, or number of lifetime exposures to trauma increase subjective peri-traumatic suffering and have been linked to increased symptom severity and qualitatively different psychiatric outcomes 112 , 113 , 114 , 115 , 116 , 117 , 118 . Evidence suggests that both qualitative and quantitative differences in rodent trauma models contribute to differences in their impact on rodent behavior and neurobiology 83 . Thus, differences in neurobiological response to various preclinical models of trauma may provide insight into the role of trauma type, duration, and chronicity in contributing to neurobiological heterogeneity among individuals with psychiatric disorders.

Types of traumatic stress exposure and 5-HT1A alterations

As discussed above, different preclinical paradigms can be seen as analogs of distinct types of traumatic events; preclinical results suggest that when controlling for all other factors, exposure to qualitatively different traumatic events (preclinical paradigms) differentially affects alterations in 5-HT1A mRNA expression. For example, preclinical studies have found that exposure to CUS (approximates chronic exposure to various unpredictable and uncontrollable traumas) led to a decrease in 5-HT1A mRNA expression in all hippocampal subfields compared to controls, but exposure to SPS (approximates single exposure to prolonged perceived life threat) led to a decrease in hippocampal 5-HT1A mRNA expression that was restricted to the CA1 and dentate gyrus 42 , 119 . In one study, chronic exposure to 20 min of FS (approximates chronic and predictable exposure to perceived threat of drowning) did not alter 5-HT1A mRNA expression in any hippocampal region 119 . Comparison of these findings reveals that animals exposed to different preclinical paradigms, and thus qualitatively different traumatic events, experienced substantially different alterations in 5-HT1A mRNA expression; trauma-induced alterations in hippocampal 5-HT1A mRNA expression may be affected by both quality and frequency of trauma exposure.

Though alterations in mRNA expression represent transcriptional alterations in gene expression, posttranscriptional mechanisms may also cause changes in gene expression, especially during dynamic processes such as those which occur after trauma exposure 120 . Posttranscriptional mechanisms include any process after the transcription of DNA into mRNA, which affect subsequent steps of gene expression 120 . Exposure to SPS, CF + SPS (SPS preceded by five days of FC), or CUS have led to concurrent increases in 5-HT1A mRNA expression and 5-HT1A expression 41 , 119 , 120 , 121 , 122 . The concurrent nature of these changes in 5-HT1A mRNA and 5-HT1A protein expression suggests that transcriptional mechanisms are at least partially responsible for the observed change in 5-HT1A expression in these studies. However, two studies found that exposure to RS (approximates prolonged and uncontrollable confinement and threat of bodily harm) or FS (approximates perceived threat of drowning) led to incongruities in 5-HT1A mRNA expression and 5-HT1A expression 123 , 124 . For example, one study found that exposure to chronic RS led to an increase in 5-HT1A mRNA expression, but a decrease in 5-HT1A expression in the prefrontal cortex 123 . The opposing direction of alterations in 5-HT1A mRNA expression and 5-HT1A expression suggests that posttranscriptional mechanisms led to the decrease in 5-HT1A expression. Furthermore, when controlling for all other factors, one study found that RS and FS exposure led to opposite changes in 5-HT1A antagonist binding through posttranscriptional mechanisms; RS led to decreases (CA3 and dentate gyrus), while FS led to increases (CA2 and cortex), though neither exposure affected 5-HT1A mRNA expression 124 . Based on these findings, the degree to which trauma exposure impacts 5-HT1A expression through transcriptional versus posttranscriptional mechanisms may vary by trauma type. Furthermore, when trauma exposure does impact 5-HT1A expression through posttranscriptional mechanisms, the direction of change and region affected may also depend upon trauma type. Taken as a whole, this evidence suggests that the impact of trauma exposure on 5-HT1A expression, including the region, direction, and mechanism of change, is influenced by and potentially dependent in part on the type of trauma an individual is exposure to.

Further supporting our proposal that different trauma types may alter 5-HT1A through different mechanisms, research suggests that alterations in the 5-HT1A repressor Freud-1 may play a role in altering 5-HT1A expression after some, but not all traumas. In one study, exposure to RS led to reduced Freud-1 mRNA and protein in the prefrontal cortex as well as the expected concurrent increase in prefrontal 5-HT1A mRNA in Sprague-Dawley rats 123 . In another study, exposure to CSD (approximates chronic exposure to interpersonal violence) led to decreased prefrontal 5-HT1A mRNA expression in Wistar rats without affecting Freud-1 mRNA expression 125 . Of note, researchers also used different strains of rats (Sprague-Dawley rats and Wistar rats), which may have contributed to observed findings. However, one study which used only one breed of rat examined the effect of nontraumatic stressors in the prefrontal cortex and found that each of four qualitatively different types of stress led to distinct alterations in both mRNA and protein levels of 5-HT1A, Freud-1, and NUDR (NUDR acts as a 5-HT1A autoreceptor repressor and 5-HT1A heteroreceptor enhancer) 126 . Overall, this evidence suggests that different types of stress, including different types of traumatic stress, can alter 5-HT1A expression through different mechanisms.

Preclinical pharmacological studies provide additional supporting evidence for our thesis that different types of traumas differentially affect 5-HT1A. Different types of trauma may differentially alter the physiological impact of 5-HT1A activity. One study found that pretreatment with the 5-HT1A agonist ipsapirone differentially affected increases in extracellular levels of adrenocorticotropic releasing hormone, corticosterone, and plasma renin concentration induced by RS, FS, and FC (approximates exposure to predictable physical harm) 127 . In addition, one study found that the 5-HT1A agonist 8-OH-DPAT attenuated the corticosterone response to FC but not RS or IES (approximates exposure to inescapable physical harm) 128 . Based on these results, the observed differential impact of trauma type on 5-HT1A alterations likely has downstream physiological consequences including altered neuro-endocrine functioning.

Though they examine different rodent strains and therefore do not include a direct comparison to other trauma types, additional studies suggest that specific trauma-induced 5-HT1A alterations may have specific behavioral consequences. For example, one study found that, in male Sprague-Dawley rats, SPS led to an increase in 5-HT1A expression in the hippocampal CA1 region as well as impaired spatial memory performance 129 . Local CA1 injection of the 5-HT1A agonist 8-OH-DPAT further exacerbated the SPS-induced impairment, suggesting an impairing effect of SPS-induced 5-HT1A upregulation in the CA1 on spatial memory 129 . By contrast, decreased 5-HT1A expression and activity in the prelimbic (PrL) cortex may be a critical mechanism of CSD-induced anxiety. One study found that, in female mandarin voles, CSD led to decreased 5-HT1A expression in the PrL, decreased PrL serotonin levels, and increased anxious behavior 130 . Local PrL injection of 8-OH-DPAT reversed the CSD-induced anxiety in exposed voles, while local PrL injection of WAY-100635 (a 5-HT1A antagonist) caused anxious behaviors in control voles 130 . Of note, in CSD-exposed voles, 5-HT1A autoreceptor expression was increased in the dorsal raphe nucleus (which projects to the PrL), suggesting that the decreased PrL serotonin levels were caused by a region-specific increase in 5-HT1A expression 130 . Overall, these results suggest that region-specific trauma-induced increases and decreases in 5-HT1A expression and activity may have impairing behavioral effects. Given that different types of trauma lead to different region-specific alterations in 5-HT1A, this suggests that the differences in behavioral impact observed in different trauma types may be related to the observed differences in 5-HT1A alterations.

Chronicity and duration of traumatic stress exposure and 5-HT1A alterations

As is the case with different types of traumas, preclinical results suggest that, when controlling for all other factors, differences in duration (time per exposure) or chronicity (days of exposure) lead to different alterations in 5-HT1A expression and 5-HT1A mRNA expression. For example, in one study, exposure to 30 min of FS led to an increase in 5-HT1A agonist binding and 5-HT1A antagonist binding in the hippocampus and cortex 124 . By contrast, exposure to only 15 min of FS did not alter 5-HT1A agonist binding or 5-HT1A antagonist binding in the hippocampus or cortex 124 . Similarly, findings from two studies suggest that exposure to 14 days of CUS led to a decrease in hippocampal 5-HT1A mRNA expression, but exposure to 7 days of the same CUS paradigm did not alter hippocampal 5-HT1A mRNA expression 42 , 119 . As the extent of trauma exposure leads to different clinical consequence in humans, preclinical evidence suggests that both duration and chronicity of exposure appear to impact 5-HT1A expression.

Differences in chronicity of trauma exposure can differentially impact 5-HT1A expression in complex ways. For example, in one study, exposure to CSD led to a transient increase in 5-HT1A binding in the claustrum, which was found when exposure lasted 2 days, but not when exposure lasted 10 or more days 43 . However, exposure to the same CSD paradigm led to a stable decrease in 5-HT1A binding in the posterior cingulate, which was found when exposure lasted 10, 21, or 28 days 43 . Exposure for 28 days also led to decreases in the parietal cortex, prefrontal cortex, regio retrobulbaris, and CA1 hippocampal region, which were not found when exposure lasted <28 days 43 . These results support a possible region-specific dose-response relationship between chronicity of trauma exposure and 5-HT1A binding. Interestingly, no change was detected in the raphe for any chronicity of CSD up to 28 days 43 . In another study, 2 h of exposure to RS led to an increase in hippocampal 5-HT1A binding when exposure lasted 1 day and a further increase in 5-HT1A binding when exposure lasted 5 days 131 . In contrast with the overall increase in hippocampal 5-HT1A binding observed between 1 and 5 days of exposure, increases in the CA4 subregion were transient; increases in 5-HT1A binding in the CA4 were observed when exposure lasted for 1 day but not when it lasted for 5 days 131 . Overall, findings suggest that changes in length of exposure may lead to distinct region-specific changes in the degree and direction of the relationship between trauma exposure and 5-HT1A expression; these changes can be transient in nature or delayed in onset. Taken together, preclinical findings support the assertion that differences in qualitative and quantitative aspects of trauma exposure contribute to variation in subsequent alterations in 5-HT1A expression.

Clinical/pharmacological implications

The exact role of 5-HT1A in the etiology of trauma-related psychiatric disorders is unclear. However, the prevailing consensus is that 5-HT1A is influential in the development of depression, anxiety, fear, and memory impairment 35 , 36 , 37 . In addition, one study finds that individuals with PTSD may have elevated 5-HT1A availability 76 . Further elucidation of 5-HT1A’s behavioral impact, including the degree to which it varies as a function of trauma history, may lead to the development of highly targeted treatments, and betterment of outcomes through personalized treatment 44 , 132 . For example, preclinical studies suggest that biased 5-HT1A agonists, which specifically target autoreceptor or heteroreceptor signaling, may be more effective in treating depression and anxiety than currently available 5-HT1A agonists 133 , 134 , 135 . In addition, recent literature suggests that drugs capable of acting on specific mechanisms of 5-HT1A expression could lead to major breakthroughs in treating depression 44 . However, targeting the correct mechanism for alteration of 5-HT1A may be critical 44 , 136 . Given the impact of trauma type and extent of exposure on 5-HT1A, we theorize that trauma history may be a crucial determinant of response to future breakthrough treatments.

In support of our theory, previous correlational studies and randomized controlled trials have found evidence to suggest that individuals with the same diagnosis but different trauma histories respond differently to currently available pharmacological treatments 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 . Thus, individuals with different trauma histories may require different pharmacological treatments, likely in part due to the differential effects of those trauma histories on gene expression. Failure to account for trauma history during pharmacological studies may obscure trauma-induced heterogeneity in responsivity, thus concealing a drug’s potential efficacy (or lack thereof) in individuals with particular trauma histories and delaying progress in clinical practice. Based on this evidence, in order to achieve personalized treatment, one must first account for the differential impact of different types of trauma and degrees of exposure.

5-HT1A as an exemplar

Though the primary focus of this review has been 5-HT1A, the implications of these findings likely extend to additional molecular targets. Multiple preclinical studies suggest that different types of trauma and degrees of exposure can lead to alterations in molecular targets other than 5-HT1A. For example, exposure to CUS led to multiple region-specific increases and decreases in dopamine D1-like receptor binding, but exposure to RS did not impact D1-like receptor binding in any of those regions 145 . Similarly, in the hippocampal CA2, exposure to RS led to an increase in serotonin-7 receptor mRNA expression but exposure to CUS did not 146 . Additional examples exist, including research focused on mu opioid and glucocorticoid receptors 147 , 148 . Similarly, multiple studies have found evidence to suggest that different types of trauma exposure and different degrees of trauma exposure differentially affect gene expression in humans 149 , 150 , 151 , 152 , 153 . For example, in one study, profiles of gene expression in peripheral blood cells which distinguished individuals with PTSD from controls were almost completely distinct (98% nonoverlapping), depending on whether subjects with PTSD had a history of childhood abuse exposure 153 . Importantly, in addition to PTSD, the impact of trauma type and degree of exposure on gene expression has been evident in individuals with MDD and borderline personality disorder 150 . Taken together, these studies provide direct evidence for the importance of trauma type and degree of exposure in modulating the effect of trauma on genetic expression, which extends beyond 5-HT1A and beyond PTSD.

Previously, we synthesized evidence to suggest that different types of traumas can alter 5-HT1A through different mechanisms, including the 5-HT1A repressor Freud-1. A closer examination of specific mechanisms of 5-HT1A alterations provides a useful paradigm for understanding the complexity of the concurrent impact of different trauma types and degrees of exposure on many molecular mechanisms. For example, the 5-HT1A repressor Freud-1 also represses the dopamine receptor D 2 154 . Thus, differences in the impact of various types of trauma on Freud-1 likely lead to differences in expression of not only 5-HT1A, but also D 2 and any other mechanisms affected by Freud-1. In addition, we provided evidence that different types of stressors differentially impact the dual-effect 5-HT1A autoreceptor repressor and 5-HT1A heteroreceptor enhancer NUDR. In addition to its effect on 5-HT1A, NUDR also regulates transcription of Proenkephalin 155 . Notably, many transcriptional and posttranscriptional mechanisms of 5-HT1A expression also affect multiple molecular targets 44 . For example, the 5-HT1A autoreceptor enhancer Pet-1 also plays a role in activating expression of the nicotinic acetylcholine receptor 156 , 157 . In addition, 5-HT1A promotors MAZ and Sp1 decrease NMDA receptor subunit type 1 promoter activity 158 , 159 . Furthermore, in addition to posttranscriptional regulation of 5-HT1A, miR-135a also regulates the serotonin transporter, PHLPP2, and FOXO1 44 . These findings illustrate the general principal that the mechanisms underlying differential impacts of trauma type and chronicity of exposure on 5-HT1A expression likely lead to differential impacts on other molecular targets as well. Furthermore, they provide insight into the fact that traumatic stressors may regulate a wide array of molecular targets through diffusely acting mechanisms.

Limitations and future directions

This paper does not provide an exhaustive review of the literature on 5-HT1A and trauma. Many studies which found alterations in 5-HT1A expression induced by rodent trauma models were excluded from mention in this work due to a lack of direct comparability arising from methodological discrepancies 58 , 160 , 161 , 162 , 163 , 164 , 165 , 166 , 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 , 176 , 177 , 178 , 179 , 180 , 181 , 182 , 183 , 184 . Future preclinical studies can further elucidate the impact of differences in trauma type and extent of exposure on changes in the expression of 5-HT1A and other molecular targets by consciously and deliberately accounting for trauma type. One particularly noteworthy gap in the current literature concerns early life trauma. To date, models of early life trauma have been associated with increases 183 , decreases 174 , or no change 184 in 5-HT1A expression. However, methodological differences (e.g., rodent strain, rodent sex, chronicity of exposure, additional experimental stressors, time since trauma exposure at sacrifice, and index of 5-HT1A expression) preclude direct comparisons between trauma models or between different developmental periods as they relate to 5-HT1A expression. Future studies should endeavor to resolve this issue.

More studies are needed in order to identify relationships between specific categories of trauma and resultant alterations in gene expression. In addition, these findings have yet to be extended to humans. Only one published study in humans has evaluated the relationship between 5-HT1A and trauma exposure, with null results 185 . Of note, however, trauma type was not controlled for and authors acknowledged that the study may have lacked sufficient power to detect an association 185 . Future studies should examine the association between trauma and 5-HT1A expression in humans, specifically with respect to differences in trauma type and chronicity of exposure. Given the known adverse impacts of aversive childhood experiences and the divergence in genetic expression associated with childhood and adult trauma, differences in developmental timing of trauma should also be considered.

While it seems clear based on the reviewed preclinical literature that trauma type and chronicity of exposure impact gene expression, no available preclinical studies examining 5-HT1A distinguish behaviorally affected and resilient individuals. In the preclinical literature, the importance of separating behaviorally affected animals from resilient animals is becoming increasingly clear 82 , 83 . Studies have found that some post-trauma alterations in gene expression that are present in the group average may only apply to affected animals, while others may only apply to resilient animals 82 , 83 . Thus, with the exception of studies that measure the behavioral effects of 5-HT1A agonists or antagonists in addition to measuring gene expression, most currently available studies do not provide information to distinguish adaptive alterations in 5-HT1A from maladaptive alterations. Future studies should apply methodology such as cut-off behavioral criteria and behavioral profiling in order to distinguish alterations in 5-HT1A that are seen in resilient animals from those seen in affected animals. Of note, cut-off behavioral criteria and behavioral profiling are applied analytically to postexposure behavioral data and do not necessarily require a change in study design 82 , 83 . Thus, it may be possible to apply these techniques to archival data. Though some research questions may require the design of new studies in order to incorporate specific behavioral effects of interest, we recommend applying cut-off behavioral criteria and/or behavioral profiling to archival data wherever feasible. In addition to being highly practical, the use of archival data is in line with ethical best practice as it does not cause any additional suffering to animals 186 .

This review focuses on the importance of considering differences in the nature and chronicity of trauma exposure in neurobiological research. However, other key variables warrant similar consideration. Specifically, recent research has emphasized the importance of sex differences, risk factors, and individual differences in response to the same trauma 82 . We propose that these two approaches need not be mutually exclusive. For example, in rodents, qualitatively different types of nontraumatic stressors have been found to lead to sex-dependent differential alterations in mRNA and density of 5-HT1A and specific 5-HT1A transcription factors 126 . Future studies should examine the degree to which the interaction of stressor type and sex extends to rodent trauma models and human trauma exposure. This approach could also be extended to other relevant risk factors, such as inherited genetic differences, which are shown to alter trauma’s impact on 5-HT1A expression as well as behavior 182 . Specific single nucleotide polymorphisms alter the ability of specific mechanisms to impact gene expression 187 . Specific mechanisms underlying the relationship between trauma and gene expression depend on trauma type and level of exposure. Therefore, future studies should investigate specific interactions between genes, sex, and trauma type as they relate to 5-HT1A expression.

Conclusions

We have presented preclinical evidence supporting our contention that differences in the type and chronicity of exposure to trauma leads to differences in the region-specific posttraumatic alterations in 5-HT1A. Furthermore, differences in the nature of trauma and extent of exposure to trauma appear to lead to differences in the mechanisms underlying changes in 5-HT1A expression; even when two different traumas lead to the same directional change in 5-HT1A expression in a given region, it is possible that different mechanisms are driving the change. Furthermore, this phenomenon does not appear to be specific to 5-HT1A and evidence suggests that it may translate to humans. Based on the evidence presented in this review, future studies aimed at understanding the differential molecular alterations that are generally associated with certain categories of trauma exposure may eventually inform a more targeted approach to pharmacological treatments for trauma-exposed individuals. In order to understand the neurobiology of trauma, it is crucial to consider both trauma type and extent of exposure.

Benjet, C. et al. The epidemiology of traumatic event exposure worldwide: results from the World Mental Health Survey Consortium. Psychol. Med. 46 , 327–343 (2016).

Article   CAS   PubMed   Google Scholar  

Guina, J. et al. Should posttraumatic stress be a disorder or a specifier? Towards improved nosology within the DSM categorical classification system. Curr. Psychiatry Rep. 19 , 66 (2017).

Article   PubMed   Google Scholar  

Bonanno, G. A. & Mancini, A. D. Beyond resilience and PTSD: mapping the heterogeneity of responses to potential trauma. Psychol. Trauma 4 , 74 (2012).

Article   Google Scholar  

Krupnick, J. L. et al. Mental health effects of adolescent trauma exposure in a female college sample: exploring differential outcomes based on experiences of unique trauma types and dimensions. Psychiatry 67 , 264–279. (2004).

Wanklyn, S. G. et al. Trauma types as differential predictors of posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and their comorbidity. Can. J. Behav. Sci. 48 , 296 (2016).

Briggs-Gowan, M. J. et al. Exposure to potentially traumatic events in early childhood: differential links to emergent psychopathology. J. Child Psychol. Psychiatry 51 , 1132–1140 (2010).

Article   PubMed   PubMed Central   Google Scholar  

Freeman, D. & Fowler, D. Routes to psychotic symptoms: trauma, anxiety and psychosis-like experiences. Psychiatry Res. 169 , 107–112 (2009).

Hall, A., Kimberly, A., Bartlett, B. A., Iverson, K. M. & Mitchell, K. S. Eating disorder symptoms in female veterans: the role of childhood, adult, and military trauma exposure. Psychol. Trauma 10 , 345 (2018).

Khan, A. et al. Examining the impact of different types of military trauma on suicidality in women veterans. Psychiatry Res. 274 , 7–11 (2019).

Goldsmith, R. E., Freyd, J. J. & DePrince, A. P. Betrayal trauma: associations with psychological and physical symptoms in young adults. J. Interpers. Violence 27 , 547–567 (2012).

Briere, J. & Runtz, M. Differential adult symptomatology associated with three types of child abuse histories. Child Abuse Negl. 14 , 357–364 (1990).

Sullivan, T. P., Fehon, D. C., Andres-Hyman, R. C., Lipschitz, D. S. & Grilo, C. M. Differential relationships of childhood abuse and neglect subtypes to PTSD symptom clusters among adolescent inpatients. J. Trauma Stress. 19 , 229–239 (2006).

Prigerson, H. G., Maciejewski, P. K. & Rosenheck, R. A. Combat trauma: trauma with highest risk of delayed onset and unresolved posttraumatic stress disorder symptoms, unemployment, and abuse among men. J. Nerv. Ment. Dis. 189 , 99–108 (2001).

Amir, M., Kaplan, Z. & Kotler, M. Type of trauma, severity of posttraumatic stress disorder core symptoms, and associated features. J. Gen. Psychol. 123 , 341–351 (1996).

Ford, J. D., Stockton, P., Kaltman, S. & Green, B. L. Disorders of extreme stress (DESNOS) symptoms are associated with type and severity of interpersonal trauma exposure in a sample of healthy young women. J. Interpers. Violence 21 , 1399–1416 (2006).

Smith, H. L., Summers, B. J., Dillon, K. H. & Cougle, J. R. Is worst-event trauma type related to PTSD symptom presentation and associated features? J. Anxiety Disord. 38 , 55–61 (2016).

Contractor, A. A., Caldas, S. V., Dolan, M., Lagdon, S. & Armour, C. PTSD’s factor structure and measurement invariance across subgroups with differing count of trauma types. Psychiatry Res. 264 , 76–84 (2018).

Hyland, P. et al. Variation in post-traumatic response: the role of trauma type in predicting ICD-11 PTSD and CPTSD symptoms. Soc. Psychiatry Psychiatr. Epidemiol. 52 , 727–736 (2017).

Kilpatrick, D. G. et al. National estimates of exposure to traumatic events and PTSD prevalence using DSM-IV and DSM-5 criteria. J. Trauma Stress 26 , 537–547 (2013).

Kessler, R. C. et al. Trauma and PTSD in the WHO world mental health surveys. Eur. J. Psychotraumatol. 8 , 1353383 (2017).

Cassiers, L. L. M. et al. Structural and functional brain abnormalities associated with exposure to different childhood trauma subtypes: a systematic review of neuroimaging findings. Front. Psychiatry 9 , 329 (2018).

Cornelis, M. C., Nugent, N. R., Amstadter, A. B. & Koenen, K. C. Genetics of post-traumatic stress disorder: review and recommendations for genome-wide association studies. Curr. Psychiatry Rep. 12 , 313–326 (2010).

Kolassa, I.-T., Kolassa, S., Ertl, V., Papassotiropoulos, A. & Dominique, J.-F. The risk of posttraumatic stress disorder after trauma depends on traumatic load and the catechol-O-methyltransferase Val158Met polymorphism. Biol. Psychiatry 67 , 304–308 (2010).

Mehta, D. & Binder, E. B. Gene× environment vulnerability factors for PTSD: the HPA-axis. Neuropharmacology 62 , 654–662 (2012).

Zannas, A. & Binder, E. Gene–environment interactions at the FKBP5 locus: sensitive periods, mechanisms and pleiotropism. Genes Brain Behav. 13 , 25–37 (2014).

Huckins, L. M. et al. Analysis of Genetically Regulated Gene Expression Identifies a Prefrontal PTSD Gene, SNRNP35, Specific to Military Cohorts. Cell Reports https://doi.org/10.1016/j.celrep.2020.107716 (2020).

Nievergelt, C. et al. 157. Large-scale genetic characterization of PTSD: addressing heterogeneity across ancestry, sex, and trauma. Biol. Psychiatry 83 , S64 (2018).

Miller, M. et al. CRP polymorphisms and DNA methylation of the AIM2 gene influence associations between trauma exposure, PTSD, and C-reactive protein. Brain Behav. Immun. 67 , 194–202 (2018).

Heim, C., Newport, D. J., Mletzko, T., Miller, A. H. & Nemeroff, C. B. The link between childhood trauma and depression: insights from HPA axis studies in humans. Psychoneuroendocrinology 33 , 693–710 (2008).

Lanius, R. A., Brand, B., Vermetten, E., Frewen, P. A. & Spiegel, D. The dissociative subtype of posttraumatic stress disorder: rationale, clinical and neurobiological evidence, and implications. Depress. Anxiety 29 , 701–708 (2012).

Menke, A. et al. Childhood trauma dependent anxious depression sensitizes HPA axis function. Psychoneuroendocrinology 98 , 22–29 (2018).

Tokuda, T. et al. Identification of depression subtypes and relevant brain regions using a data-driven approach. Sci. Rep. 8 , 14082 (2018).

Article   PubMed   PubMed Central   CAS   Google Scholar  

Gaudiano, B. A. & Zimmerman, M. The relationship between childhood trauma history and the psychotic subtype of major depression. Acta Psychiatr. Scand. 121 , 462–470 (2010).

Croarkin, P. E. Indexing the neurobiology of psychotic depression with resting state connectivity: insights from the STOP-PD study. EBioMedicine 37 , 32–33 (2018).

Kaufman, J., DeLorenzo, C., Choudhury, S. & Parsey, R. The 5-HT1A receptor in major depressive disorder. Eur. Neuropsychopharmacol. 26 , 397–410 (2016).

Article   CAS   PubMed   PubMed Central   Google Scholar  

Garcia-Garcia, A. L., Newman-Tancredi, A. & Leonardo, E. D. P5-HT 1A receptors in mood and anxiety: recent insights into autoreceptor versus heteroreceptor function. Psychopharmacology 231 , 623–636 (2014).

Ögren, S. O. et al. The role of 5-HT 1A receptors in learning and memory. Behav. Brain Res. 195 , 54–77 (2008).

Article   PubMed   CAS   Google Scholar  

Glikmann-Johnston, Y., Saling, M. M., Reutens, D. C. & Stout, J. C. Hippocampal 5-HT1A receptor and spatial learning and memory. Front. Pharmacol. 6 , 289 (2015).

Pattij, T. & Schoffelmeer, A. N. Serotonin and inhibitory response control: focusing on the role of 5-HT1A receptors. Eur. J. Pharmacol. 753 , 140–145 (2015).

Mann, J. J., Arango, V., Marzuk, P. M., Theccanat, S. & Reis, D. Evidence for the 5-HT hypothesis of suicide a review of post-mortem studies. Br. J. Psychiatry 155 , 7–14 (1989).

Luo, F. F., Han, F. & Shi, Y. X. Changes in 5-HT1A receptor in the dorsal raphe nucleus in a rat model of post-traumatic stress disorder. Mol. Med. Rep. 4 , 843–847 (2011).

CAS   PubMed   Google Scholar  

López, J. F., Liberzon, I., Vázquez, D. M., Young, E. A. & Watson, S. J. Serotonin 1A receptor messenger RNA regulation in the hippocampus after acute stress. Biol. Psychiatry 45 , 934–937 (1999).

Flùgge, G. Dynamics of central nervous 5-HT1A-receptors under psychosocial stress. J. Neurosci. 15 , 7132–7140 (1995).

Albert, P. R., Le François, B. & Vahid-Ansari, F. Genetic, epigenetic and posttranscriptional mechanisms for treatment of major depression: the 5-HT1A receptor gene as a paradigm. J. Psychiatry Neurosci. 44 , 164 (2019).

Ito, H., Halldin, C. & Farde, L. Localization of 5-HT1A receptors in the living human brain using [carbonyl-11C] WAY-100635: PET with anatomic standardization technique. J. Nucl. Med . 40 , 102–109 (1999).

Kia, H. K., Brisorgueil, M. J., Hamon, M., Calas, A. & Vergé, D. Ultrastructural localization of 5-hydroxytryptamine1A receptors in the rat brain. J. Neurosci. Res. 46 , 697–708 (1996).

Hall, H. et al. Autoradiographic localization of 5-HT1A receptors in the post-mortem human brain using [3H] WAY-100635 and [11C] way-100635. Brain Res. 745 , 96–108 (1997).

Weissmann-Nanopoulos, D., Mach, E., Magre, J., Demassey, Y. & Pujol, J.-F. Evidence for the localization of 5HT1A binding sites on serotonin containing neurons in the raphe dorsalis and raphe centralis nuclei of the rat brain. Neurochem. Int. 7 , 1061–1072 (1985).

Li, X. et al. 5-HT1A receptor agonist affects fear conditioning through stimulations of the postsynaptic 5-HT1A receptors in the hippocampus and amygdala. Eur. J. Pharmacol. 532 , 74–80 (2006).

Knapp, C. M. & Kornetsky, C. Neural basis of pleasure and reward. Handbook of Neuroscience for the Behavioral Sciences , Vol. 2, 781–806 (John Wiley & Sons, 2009).

Depoortère, R. et al. F15599, a preferential post-synaptic 5-HT1A receptor agonist: activity in models of cognition in comparison with reference 5-HT1A receptor agonists. Eur. Neuropsychopharmacol. 20 , 641–654 (2010).

Li, Q. et al. Medial hypothalamic 5-hydroxytryptamine (5-HT) 1A receptors regulate neuroendocrine responses to stress and exploratory locomotor activity: application of recombinant adenovirus containing 5-HT1A sequences. J. Neurosci. 24 , 10868–10877 (2004).

Razoux, F. et al. Transgenerational disruption of functional 5-HT 1A R-induced connectivity in the adult mouse brain by traumatic stress in early life. Mol. Psychiatry 22 , 519 (2017).

Fink, K. B. & Göthert, M. 5-HT receptor regulation of neurotransmitter release. Pharmacol. Rev. 59 , 360–417 (2007).

Rojas, P. S. & Fiedler, J. L. What do we really know about 5-HT1A receptor signaling in neuronal cells? Front. Cell Neurosci. 10 , 272 (2016).

Osei-Owusu, P., James, A., Crane, J. & Scrogin, K. E. 5-Hydroxytryptamine 1A receptors in the paraventricular nucleus of the hypothalamus mediate oxytocin and adrenocorticotropin hormone release and some behavioral components of the serotonin syndrome. J. Pharmacol. Exp. Ther. 313 , 1324–1330 (2005).

Choi, I.-S., Cho, J.-H. & Jang, I.-S. 5-Hydroxytryptamine 1A receptors inhibit glutamate release in rat medullary dorsal horn neurons. Neuroreport 24 , 399–403 (2013).

Harvey, B. H., Naciti, C., Brand, L. & Stein, D. J. Endocrine, cognitive and hippocampal/cortical 5HT1A/2A receptor changes evoked by a time-dependent sensitisation (TDS) stress model in rats. Brain Res. 983 , 97–107 (2003).

Poulos, C. X., Parker, J. & Le, A. Dexfenfluramine and 8-OH-DPAT modulate impulsivity in a delay-of-reward paradigm: implications for a correspondence with alcohol consumption. Behav. Pharmacol. 7 , 395–399 (1996).

Celada, P., Puig, M. V., Amargós-Bosch, M., Adell, A. & Artigas, F. The therapeutic role of 5-HT1A and 5-HT2A receptors in depression. J. Psychiatry Neurosci. 29 , 252 (2004).

PubMed   PubMed Central   Google Scholar  

Blier, P. & Ward, N. M. Is there a role for 5-HT1A agonists in the treatment of depression? Biol. Psychiatry 53 , 193–203 (2003).

Charuvastra, A. & Cloitre, M. Social bonds and posttraumatic stress disorder. Annu. Rev. Psychol. 59 , 301–328 (2008).

Davis, M. T., Witte, T. K. & Weathers, F. W. Posttraumatic stress disorder and suicidal ideation: the role of specific symptoms within the framework of the interpersonal-psychological theory of suicide. Psychol. Trauma 6 , 610 (2014).

Bell, R. & Hobson, H. 5-HT1A receptor influences on rodent social and agonistic behavior: a review and empirical study. Neurosci. Biobehav. Rev. 18 , 325–338 (1994).

de Boer, S. F. & Koolhaas, J. M. 5-HT1A and 5-HT1B receptor agonists and aggression: a pharmacological challenge of the serotonin deficiency hypothesis. Eur. J. Pharmacol. 526 , 125–139 (2005).

Aubert, Y. et al. Flibanserin and 8-OH-DPAT implicate serotonin in association between female marmoset monkey sexual behavior and changes in pair-bond quality. J. Sex. Med. 9 , 694–707 (2012).

Albert, P. R. & Le François, B. Modifying 5-HT1A receptor gene expression as a new target for antidepressant therapy. Front. Neurosci. 4 , 35 (2010).

CAS   PubMed   PubMed Central   Google Scholar  

Albert, P. R. & Fiori, L. M. Transcriptional dys-regulation in anxiety and major depression: 5-HT1A gene promoter architecture as a therapeutic opportunity. Curr. Pham. Des. 20 , 3738–3750 (2014).

Meneses, A. & Perez-Garcia, G. 5-HT1A receptors and memory. Neurosci. Biobehav. Rev. 31 , 705–727 (2007).

Ögren, S. O. et al. The role of 5-HT1A receptors in learning and memory. Behav. Brain Res. 195 , 54–77 (2008).

Bert, B., Fink, H., Rothe, J., Walstab, J. & Bönisch, H. Learning and memory in 5-HT1A-receptor mutant mice. Behav. Brain Res. 195 , 78–85 (2008).

Tomkins, D. M., Sellers, E. M. & Fletcher, P. Median and dorsal raphe injections of the 5-HT1A agonist, 8-OH-DPAT, and the GABAA agonist, muscimol, increase voluntary ethanol intake in Wistar rats. Neuropharmacology 33 , 349–358 (1994).

Cryan, J. F. & Leonard, B. E. 5-HT1A and beyond: the role of serotonin and its receptors in depression and the antidepressant response. Hum. Psychopharmacol. 15 , 113–135 (2000).

Sniecikowska, J., Newman-Tancredi, A. & Kolaczkowski, M. From receptor selectivity to functional selectivity: the rise of biased agonism in 5-HT1A receptor drug discovery. Curr. Top. Med. Chem. 19 , 2393–2420 (2019).

Jovanovic, H., Perski, A., Berglund, H. & Savic, I. Chronic stress is linked to 5-HT1A receptor changes and functional disintegration of the limbic networks. Neuroimage 55 , 1178–1188 (2011).

Sullivan, G. M. et al. Higher in vivo serotonin-1a binding in posttraumatic stress disorder: a PET study with [11C] WAY-100635. Depress. Anxiety 30 , 197–206 (2013).

Bonne, O. et al. No change in serotonin type 1A receptor binding in patients with posttraumatic stress disorder. Am. J. Psychiatry 162 , 383–385 (2005).

Milak, M. S. et al. Higher 5-HT1A autoreceptor binding as an endophenotype for major depressive disorder identified in high risk offspring—a pilot study. Psychiatry Res. 276 , 15–23 (2018).

Miller, J. M. et al. Elevated serotonin 1A binding in remitted major depressive disorder: evidence for a trait biological abnormality. Biol. Psychiatry 34 , 2275 (2009).

CAS   Google Scholar  

Stein, J. Y., Wilmot, D. V. & Solomon, Z. Does one size fit all? Nosological, clinical, and scientific implications of variations in PTSD Criterion A. J. Anxiety Disord. 43 , 106–117 (2016).

Olson, E. A. et al. Childhood maltreatment experiences are associated with altered diffusion in occipito-temporal white matter pathways. Brain Behav. 10 , e01485 (2019).

Richter-Levin, G., Stork, O. & Schmidt, M. V. Animal models of PTSD: a challenge to be met. Mol. Psychiatry 1 , 1135–1156 (2018).

Google Scholar  

Whitaker, A. M., Gilpin, N. W. & Edwards, S. Animal models of post-traumatic stress disorder and recent neurobiological insights. Behav. Pharmacol. 25 , 398 (2014).

Yamamoto, S. et al. Single prolonged stress: toward an animal model of posttraumatic stress disorder. Depress. Anxiety 26 , 1110–1117 (2009).

Wilson, C. B., Ebenezer, P. J., McLaughlin, L. D. & Francis, J. Predator exposure/psychosocial stress animal model of post-traumatic stress disorder modulates neurotransmitters in the rat hippocampus and prefrontal cortex. PLoS ONE 9 , e89104 (2014).

Wilson, M. A., Grillo, C. A., Fadel, J. R. & Reagan, L. P. Stress as a one-armed bandit: Differential effects of stress paradigms on the morphology, neurochemistry and behavior in the rodent amygdala. Neurobiol. Stress 1 , 195–208 (2015).

Almeida, P., Trovo, M., Tokumoto, A., Pereira, A. & Padovan, C. Role of serotonin 1A receptors in the median raphe nucleus on the behavioral consequences of forced swim stress. J. Psychopharmacol. 27 , 1134–1140 (2013).

Ježek, K. et al. Stress-induced out-of-context activation of memory. PLoS Biol. 8 , 12 (2010).

Article   CAS   Google Scholar  

Niknazar, S. et al. Effect of maternal stress prior to conception on hippocampal BDNF signaling in rat offspring. Mol. Neurobiol. 54 , 6436–45. (2017).

Linnstaedt, S. D. et al. Genetic variant rs3750625 in the 3′ UTR of ADRA2A affects stress-dependent acute pain severity after trauma and alters a microRNA-34a regulatory site. Pain 158 , 230 (2017).

Serchov, T. et al. Increased signaling via adenosine A1 receptors, sleep deprivation, imipramine, and ketamine inhibit depressive-like behavior via induction of Homer1a. Neuron 87 , 549–562 (2015).

Gomez, J., Haas, N. A. & Schwarz, J. M. An IL-6 receptor antagonist attenuates postpartum anhedonia, but has no effect on anhedonia precipitated by subchronic stress in female rats. Psychopharmacology 236 , 2983–2995 (2019).

Qi, X., Lin, W., Li, J., Pan, Y. & Wang, W. The depressive-like behaviors are correlated with decreased phosphorylation of mitogen-activated protein kinases in rat brain following chronic forced swim stress. Behav. Brain Res. 175 , 233–240 (2006).

Chen, L. et al. Activation of CRF/CRFR1 signaling in the basolateral nucleus of the amygdala contributes to chronic forced swim-induced depressive-like behaviors in rats. Behav. Brain Res. 338 , 134–142 (2018).

Qi, X. et al. Fluoxetine increases the activity of the ERK-CREB signal system and alleviates the depressive-like behavior in rats exposed to chronic forced swim stress. Neurobiol. Dis. 31 , 278–285 (2008).

Liu, R. et al. Citalopram alleviates chronic stress induced depression-like behaviors in rats by activating GSK3β signaling in dorsal hippocampus. Brain Res. 1467 , 10–17 (2012).

Pan, Y. et al. The effects of central pro-and anti-inflammatory immune challenges on depressive-like behavior induced by chronic forced swim stress in rats. Behav. Brain Res. 247 , 232–240 (2013).

Bai, Y., Zhang, Y., Jiang, S., Zheng, X. & Liu, Z. The effects of acute stress on consummatory and motivational responses for sucrose in rats after long-term withdrawal from morphine. Psychopharmacology 236 , 3197–208. (2019).

Kaur, G. & Kulkarni, S. Differential effect of a polyherbal formulation-OB-200G in male and female mice subjected to forced swim stress. Indian J. Physiol. Pharmacol. 44 , 281–289 (2000).

Christianson, J. P., Drugan, R. C., Flyer, J. G., Watkins, L. R. & Maier, S. F. Anxiogenic effects of brief swim stress are sensitive to stress history. Prog. Neuropsychopharmacol. Biol. Psychiatry 44 , 17–22 (2013).

Bernal-Morales, B., Guillén-Ruiz, G., Cueto-Escobedo, J., Rodríguez-Landa, J. F. & Contreras, C. M. Sensitivity to diazepam after a single session of forced swim stress in weaning Wistar rats. Acta Pharm. 68 , 381–388 (2018).

Kumar, A., Garg, R., Gaur, V. & Kumar, P. Venlafaxine involves nitric oxide modulatory mechanism in experimental model of chronic behavior despair in mice. Brain Res. 1311 , 73–80 (2010).

Varlinskaya, E. I., Johnson, J. M., Deak T. & Diaz M. R. Adolescent forced swim stress increases social anxiety-like behaviors and alters the dynorphin/kappa opioid receptor system in the basolateral amygdala of males. bioRxiv 512350. https://doi.org/10.1101/512350 (2019).

Habr, S. F., Macrini, D. J., Spinosa, H. D. S., Florio, J. C. & Bernardi, M. M. Repeated forced swim stress has additive effects in anxiety behavior and in cathecolamine levels of adult rats exposed to deltamethrin. Neurotoxicol. Teratol. 46 , 57–61 (2014).

Shioda, N. et al. Dopamine D2L receptor deficiency causes stress vulnerability through 5-HT1A receptor dysfunction in serotonergic neurons. J. Neurosci. 39 , 7551–7563 (2019).

Niknazar, S. et al. Comparison of the adulthood chronic stress effect on hippocampal BDNF signaling in male and female rats. Mol. Neurobiol. 53 , 4026–4033 (2016).

Anuradha, H., Srikumar, B., Rao, B. S. & Lakshmana, M. Euphorbia hirta reverses chronic stress-induced anxiety and mediates its action through the GABA A receptor benzodiazepine receptor-Cl− channel complex. J. Neural Transm. 115 , 35–42 (2008).

Borsoi, M. et al. Immobility behavior during the forced swim test correlates with BNDF levels in the frontal cortex, but not with cognitive impairments. Physiol. Behav. 140 , 79–88 (2015).

Anderson, R. I., Lopez, M. F. & Becker, H. C. Forced swim stress increases ethanol consumption in C57BL/6J mice with a history of chronic intermittent ethanol exposure. Psychopharmacology 233 , 2035–2043 (2016).

Kondam, A., Kate, N. N. & Lakshmi, G. Effect of forced swim stress on wistar albino rats in various behavioral parameters. Int. J. Med. Res. Health Sci. 1 , 7–12 (2012).

Huang, Y. L., Chen, S. H., Su, Y. J. & Kung, Y. W. Attachment dimensions and post-traumatic symptoms following interpersonal traumas versus impersonal traumas in young adults in Taiwan. Stress Health 33 , 233–243 (2017).

Green, B. L. et al. Outcomes of single versus multiple trauma exposure in a screening sample. J. Trauma Stress. 13 , 271–286 (2000).

Maercker, A., Beauducel, A. & Schützwohl, M. Trauma severity and initial reactions as precipitating factors for posttraumatic stress symptoms and chronic dissociation in former political prisoners. J. Trauma Stress 13 , 651–660 (2000).

Chen, Y. et al. Different regional gray matter loss in recent onset PTSD and non PTSD after a single prolonged trauma exposure. PLoS ONE 7 , e48298 (2012).

Van der Kolk, B. A., Roth, S., Pelcovitz, D., Sunday, S. & Spinazzola, J. Disorders of extreme stress: the empirical foundation of a complex adaptation to trauma. J. Trauma Stress 18 , 389–399 (2005).

Overstreet, S. & Mathews, T. Challenges associated with exposure to chronic trauma: using a public health framework to foster resilient outcomes among youth. Psychol. Sch. 48 , 738–754 (2011).

Dorahy, M. J. et al. Complex PTSD, interpersonal trauma and relational consequences: findings from a treatment-receiving Northern Irish sample. J. Affect. Disord. 112 , 71–80 (2009).

Gillespie, C. F. et al. Trauma exposure and stress-related disorders in inner city primary care patients. Gen. Hosp. Psychiatry 31 , 505–514 (2009).

López, J. F., Chalmers, D. T., Little, K. Y. & Watson, S. J. Regulation of serotonin1A, glucocorticoid, and mineralocorticoid receptor in rat and human hippocampus: implications for the neurobiology of depression. Biol. Psychiatry 43 , 547–573 (1998).

Liu, Y., Beyer, A. & Aebersold, R. On the dependency of cellular protein levels on mRNA abundance. Cell 165 , 535–550 (2016).

Liu, D. et al. Changes in 5-HT1A receptor expression in the oculomotor nucleus in a rat model of post-traumatic stress disorder. J. Mol. Neurosci. 49 , 360–368 (2013).

Xiang, M. et al. Stimulation of anxiety-like behavior via ERK pathway by competitive serotonin receptors 2A and 1A in post-traumatic stress disordered mice. Neurosignals 25 , 39–53 (2017).

Iyo, A. H. et al. Differential regulation of the serotonin 1 A transcriptional modulators five prime repressor element under dual repression-1 and nuclear-deformed epidermal autoregulatory factor by chronic stress. Neuroscience 163 , 1119–1127 (2009).

Raghupathi, R. K. & McGonigle, P. Differential effects of three acute stressors on the serotonin 5-HT1A receptor system in rat brain. Neuroendocrinology 65 , 246–258 (1997).

Kieran, N., Ou, X.-M. & Iyo, A. H. Chronic social defeat downregulates the 5-HT1A receptor but not Freud-1 or NUDR in the rat prefrontal cortex. Neurosci. Lett. 469 , 380–384 (2010).

Szewczyk, B. et al. Stress-induced alterations in 5-HT1A receptor transcriptional modulators NUDR and Freud-1. Int J. Neuropsychopharmacol. 17 , 1763–1775 (2014).

Rittenhouse, P. A. et al. Comparison of neuroendocrine and behavioral effects of ipsapirone, a 5-HT1A agonist, in three stress paradigms: immobilization, forced swim and conditioned fear. Brain Res. 580 , 205–214 (1992).

Saphier, D., Farrar, G. E. & Welch, J. E. Differential inhibition of stress-induced adrenocortical responses by 5-HT1A agonists and by 5-HT2 and 5-HT3 antagonists. Psychoneuroendocrinology 20 , 239–257 (1995).

Lin, L., Liu, G. & Zhang, Y. Research on the effects of 5-HT1 A receptor in hippocampal CA1 region in cognition of PTSD rats. Adv. Eng. Res . 107 , abstr. (2017).

Wang, L. et al. Serotonin signaling trough prelimbic 5-HT1A receptors modulates CSDS-induced behavioral changes in adult female voles. Int J. Neuropsychopharmacol. 22 , 208–220 (2019).

Mendelson, S. D. & McEwen, B. S. Autoradiographic analyses of the effects of restraint-induced stress on 5-HT1A, 5-HT1C and 5-HT2 receptors in the dorsal hippocampus of male and female rats. Neuroendocrinology 54 , 454–461 (1991).

Newman-Tancredi, A., Albert, P. R., & Sumiyoshi, T. In: Schizophrenia Research: Recent Advances 1st edn, Vol. 1 (ed Sumiyoshi, T.) Ch. 15 (Nova Science Publishers, Hauppauge, 2012).

Newman-Tancredi, A. Biased agonism at serotonin 5-HT1A receptors: preferential postsynaptic activity for improved therapy of CNS disorders. Neuropsychiatry 1 , 149 (2011).

Assié, M. B., Lomenech, H., Ravailhe, V., Faucillon, V. & Newman-Tancredi, A. Rapid desensitization of somatodendritic 5-HT1A receptors by chronic administration of the high-efficacy 5-HT1A agonist, F13714: a microdialysis study in the rat. Br. J. Pharmacol. 149 , 170–178 (2006).

Assi, M.-B. et al. F15599, a highly selective post-synaptic 5-HT1A receptor agonist: in-vivo profile in behavioural models of antidepressant and serotonergic activity. Int. J. Neuropsychopharmacol. 13 , 1285–1298 (2010).

Artigas, F., Celada, P. & Bortolozzi, A. Can we increase the speed and efficacy of antidepressant treatments? Part II. Glutamatergic and RNA interference strategies. Eur. Neuropsychopharmacol. 28 , 457–482 (2018).

Nemeroff, C. B. et al. Differential responses to psychotherapy versus pharmacotherapy in patients with chronic forms of major depression and childhood trauma. Proc. Natl Acad. Sci. 100 , 14293–14296 (2003).

Nanni, V., Uher, R. & Danese, A. Childhood maltreatment predicts unfavorable course of illness and treatment outcome in depression: a meta-analysis. Am. J. Psychiatry 169 , 141–151 (2012).

Shirk, S. R. & Karver, M. Prediction of treatment outcome from relationship variables in child and adolescent therapy: a meta-analytic review. J. Consult Clin. Psychol. 71 , 452 (2003).

Asarnow, J. R. et al. Treatment of selective serotonin reuptake inhibitor—resistant depression in adolescents: predictors and moderators of treatment response. J. Am. Acad. Child Adolesc. Psychiatry 48 , 330–339 (2009).

Lewis, C. C. et al. Impact of childhood trauma on treatment outcome in the Treatment for Adolescents with Depression Study (TADS). J. Am. Acad. Child Adolesc. Psychiatry 49 , 132–140 (2010).

PubMed   Google Scholar  

Shamseddeen, W. et al. Impact of physical and sexual abuse on treatment response in the Treatment of Resistant Depression in Adolescent Study (TORDIA). J. Am. Acad. Child Adolesc. Psychiatry 50 , 293–301 (2011).

Shavitt, R. G. et al. The impact of trauma and post-traumatic stress disorder on the treatment response of patients with obsessive-compulsive disorder. Eur. Arch. Psychiatry Clin. Neurosci. 260 , 91–99 (2010).

Williams, L. M., Debattista, C., Duchemin, A., Schatzberg, A. & Nemeroff, C. Childhood trauma predicts antidepressant response in adults with major depression: data from the randomized international study to predict optimized treatment for depression. Transl. Psychiatry 6 , e799 (2016).

Rasheed, N. et al. Differential response of central dopaminergic system in acute and chronic unpredictable stress models in rats. Neurochem. Res. 35 , 22–32 (2010).

Yau, J. L., Noble, J. & Seckl, J. R. Acute restraint stress increases 5-HT7 receptor mRNA expression in the rat hippocampus. Neurosci. Lett. 309 , 141–144 (2001).

Yamamoto, M. et al. Effects of single and repeated prolonged stress on mu-opioid receptor mRNA expression in rat gross hypothalamic and midbrain homogenates. Brain Res. 980 , 191–196 (2003).

Paskitti, M., McCreary, B. & Herman, J. Stress regulation of adrenocorticosteroid receptor gene transcription and mRNA expression in rat hippocampus: time-course analysis. Mol. Brain Res. 80 , 142–152 (2000).

McGowan, P. O. et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat. Neurosci. 12 , 342 (2009).

Perroud, N. et al. Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma. Transl. Psychiatry 1 , e59 (2011).

Smith, A. K. et al. Differential immune system DNA methylation and cytokine regulation in post-traumatic stress disorder. Am. J. Med. Genet. B Neuropsychiatr. Genet. 156 , 700–708 (2011).

Breen, M. S. et al. PTSD blood transcriptome mega-analysis: shared inflammatory pathways across biological sex and modes of trauma. Neuropsychopharmacology 43 , 469 (2018).

Mehta, D. et al. Childhood maltreatment is associated with distinct genomic and epigenetic profiles in posttraumatic stress disorder. Proc. Natl Acad. Sci. 110 , 8302–8307 (2013).

Rogaeva, A., Ou, X.-M., Jafar-Nejad, H., Lemonde, S. & Albert, P. R. Differential repression by Freud-1/CC2D1A at a polymorphic site in the dopamine-D2 receptor gene. J. Biol. Chem. 282 , 20897–20905 (2007).

Huggenvik, J. I. et al. Characterization of a nuclear deformed epidermal autoregulatory factor-1 (DEAF-1)-related (NUDR) transcriptional regulator protein. Mol. Endorinol. 12 , 1619–1639 (1998).

Jacobsen, K. X., Czesak, M., Deria, M., Le François, B. & Albert, P. R. Region-specific regulation of 5-HT1A receptor expression by Pet-1-dependent mechanisms in vivo. J. Neurochem. 116 , 1066–1076 (2011).

Fyodorov, D., Nelson, T. & Deneris, E. Pet-1, a novel ETS domain factor that can activate neuronal nAchR gene transcription. J. Neurobiol. 34 , 151–163 (1998).

Okamoto, S.-I., Sherman, K., Bai, G. & Lipton, S. A. Effect of the ubiquitous transcription factors, SP1 and MAZ, on NMDA receptor subunit type 1 (NR1) expression during neuronal differentiation. Mol. Brain Res. 107 , 89–96 (2002).

Parks, C. L. & Shenk, T. The serotonin 1a receptor gene contains a TATA-less promoter that responds to MAZ and Sp1. J. Biol. Chem. 271 , 4417–4430 (1996).

Lin, L., Liu, G. & Sun, M. Effect of 5-HT1 A receptor in hippocampal CA1 region on spatial memory of PTSD rats. Chin. J. Pathophysiol. 33 , 98–103 (2017).

Steciuk, M., Kram, M., Kramer, G. L. & Petty, F. Acute stress does not alter 5-HT1A receptor density. Prog. Neuropsychopharmacol. Biol. Psychiatry 24 , 155–161 (2000).

Fogaça, M. V., Reis, F., Campos, A. & Guimarães, F. S. Effects of intra-prelimbic prefrontal cortex injection of cannabidiol on anxiety-like behavior: involvement of 5HT1A receptors and previous stressful experience. Eur. Neuropsychopharmacol. 24 , 410–419 (2014).

Kim, M. H. & Leem, Y. H. Chronic exercise improves repeated restraint stress-induced anxiety and depression through 5HT1A receptor and cAMP signaling in hippocampus. J. Exerc Nutr. Biochem. 18 , 97 (2014).

Van Riel, E., Meijer, O., Steenbergen, P. & Joels, M. Chronic unpredictable stress causes attenuation of serotonin responses in cornu ammonis 1 pyramidal neurons. Neuroscience 120 , 649–658 (2003).

Ossowska, G. et al. Brain monoamine receptors in a chronic unpredictable stress model in rats. J. Neural Transm. 108 , 311–319 (2001).

Watanabe, Y., Sakai, R. R., McEwen, B. S. & Mendelson, S. Stress and antidepressant effects on hippocampal and cortical 5-HT1A and 5-HT2 receptors and transport sites for serotonin. Brain Res. 615 , 87–94 (1993).

Ferretti, C., Blengio, M., Gamalero, S. R. & Ghi, P. Biochemical and behaviour changes induced by acute stress in a chronic variate stress model of depression: the effect of amitriptyline. Eur. J. Pharmacol. 280 , 19–26 (1995).

Flügge, G., Kramer, M., Rensing, S. & Fuchs, E. 5HT1A-receptors and behaviour under chronic stress: selective counteraction by testosterone. Eur. J. Neurosci. 10 , 2685–2693 (1998).

Morrison, K. E., Swallows, C. L. & Cooper, M. A. Effects of dominance status on conditioned defeat and expression of 5-HT1A and 5-HT2A receptors. Physiol. Behav. 104 , 283–920 (2011).

Ul’yana, A. B., Bondar, N. P., Filipenko, M. L. & Kudryavtseva, N. N. Downregulation of serotonergic gene expression in the Raphe nuclei of the midbrain under chronic social defeat stress in male mice. Mol. Neurobiol. 48 , 13–21 (2013).

Cooper, M. A., Grober, M. S., Nicholas, C. & Huhman, K. L. Aggressive encounters alter the activation of serotonergic neurons and the expression of 5-HT1A mRNA in the hamster dorsal raphe nucleus. Neuroscience 161 , 680–690 (2009).

Ohi, K., Mikuni, M. & Takahashi, K. Stress adaptation and hypersensitivity in 5-HT neuronal systems after repeated foot shock. Pharmacol. Biochem. Behav. 34 , 603–608 (1989).

Campos, A. C., Ferreira, F. R. & Guimarães, F. S. Cannabidiol blocks long-lasting behavioral consequences of predator threat stress: possible involvement of 5HT1A receptors. J. Psychiatr. Res. 46 , 1501–1510 (2012).

Franklin, T. B., Linder, N., Russig, H., Thöny, B. & Mansuy, I. M. Influence of early stress on social abilities and serotonergic functions across generations in mice. PloS ONE 6 , e21842 (2011).

Maniam, J. & Morris, M. J. Voluntary exercise and palatable high-fat diet both improve behavioural profile and stress responses in male rats exposed to early life stress: role of hippocampus. Psychoneuroendocrinology 35 , 1553–1564 (2010).

Vázquez, D. M., Eskandari, R., Zimmer, C. A., Levine, S. & López, J. F. Brain 5-HT receptor system in the stressed infant rat: implications for vulnerability to substance abuse. Psychoneuroendocrinology 27 , 245–272 (2002).

Vicentic, A. et al. Maternal separation alters serotonergic transporter densities and serotonergic 1A receptors in rat brain. Neuroscience 140 , 355–365 (2006).

Li, M., Xue, X., Shao, S., Shao, F. & Wang, W. Cognitive, emotional and neurochemical effects of repeated maternal separation in adolescent rats. Brain Res. 1518 , 82–90 (2013).

Shishkina, G., Kalinina, T. & Dygalo, N. Effects of swim stress and fluoxetine on 5-HT1A receptor gene expression and monoamine metabolism in the rat brain regions. Cell. Mol. Neurobiol. 32 , 787–794 (2012).

Shishkina, G. T., Kalinina, T. S., Berezova, I. V. & Dygalo, N. N. Stress-induced activation of the brainstem Bcl-xL gene expression in rats treated with fluoxetine: correlations with serotonin metabolism and depressive-like behavior. Neuropharmacology 62 , 177–183 (2012).

Briones-Aranda, A., Rocha, L. & Picazo, O. Influence of forced swimming stress on 5-HT1A receptors and serotonin levels in mouse brain. Prog. Neuropsychopharmacol. Biol. Psychiatry 29 , 275–281 (2005).

Paré, W. P. & Tejani-Butt, S. M. Effect of stress on the behavior and 5-HT system in Sprague-Dawley and Wistar Kyoto rat strains. Integr. Physiol. Behav. Sci. 31 , 112–121 (1996).

Bravo, J. A., Dinan, T. G. & Cryan, J. F. Early-life stress induces persistent alterations in 5-HT1A receptor and serotonin transporter mRNA expression in the adult rat brain. Front. Mol. Neurosci. 7 , 24 (2014).

Van Riel, E., Van Gemert, N. G., Meijer, O. C. & Joëls, M. Effect of early life stress on serotonin responses in the hippocampus of young adult rats. Synapse 53 , 11–19 (2004).

Sullivan, G. M. et al. Positron emission tomography quantification of serotonin1A receptor binding in suicide attempters with major depressive disorder. JAMA Psychiatry 72 , 169–178 (2015).

Festing, S. & Wilkinson, R. The ethics of animal research. EMBO Rep. 8 , 526–530 (2007).

Lemonde, S., Du, L., Bakish, D., Hrdina, P. & Albert, P. R. Association of the C Chronic unpredictable stress causes attenuation of serotonin responses in cornu ammonis 1 pyramidal neurons(−1019) G 5-HT1A functional promoter polymorphism with antidepressant response. Internatio J. Neuropsychopharmacol. 7 , 501–506 (2004).

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The authors would like to thank Maddy Ryan for her assistance with this paper.

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Lewis, M.W., Jones, R.T. & Davis, M.T. Exploring the impact of trauma type and extent of exposure on posttraumatic alterations in 5-HT1A expression. Transl Psychiatry 10 , 237 (2020). https://doi.org/10.1038/s41398-020-00915-1

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The Core Curriculum on Childhood Trauma (CCCT) is designed to raise the standard of care nationwide for youth and families who have experienced trauma by raising the standard of education and training in core principles of childhood traumatic stress for their care providers.

A major initiative undertaken by the UCLA-Duke University National Center for Child Traumatic Stress (NCCTS) and its partners in the National Child Traumatic Stress Network, the CCCT is being implemented across the US in settings that include community-based mental health centers; teaching hospitals; graduate schools; terminal undergraduate programs; and internship, residency, and post-doctoral training programs. Many sites that have adopted the CCCT implement it in conjunction with training on manualized interventions.

The CCCT is an experiential learning tool that engages learners in a small-group setting to discuss and reason their way through detailed case studies. The Curriculum uses a highly interactive problem-based approach to help learners acquire trauma-informed knowledge and skills in critical reasoning, judgment, and decision-making. Instead of scripted lessons, the Curriculum contains a variety of elements designed to be flexibly incorporated by trained facilitators to achieve specific learning objectives.

Basic elements of the CCCT include:

• Six General Learning Objectives provide a basic framework that encompasses and supports all Core Curriculum elements. This feature provides learning facilitators with great flexibility in selecting from a wide variety of case vignettes, structured exercises, and assessment tools while staying aligned with the General Learning Objectives. 
• The 12 Core Concepts for Understanding Traumatic Stress Responses in Children and Families serve as the Curriculum’s primary conceptual framework for organizing foundational knowledge about trauma-informed care.
• Problem-Based Learning (“PBL”), an instructional method in which learners work in small groups, under the guidance of a trained facilitator, to explore multiple perspectives and find solutions to complex problems described in case studies. In its basic form, the CCCT uses a four-step PBL process comprised of Facts, Hunches and Hypotheses, Next Steps, and Learning Issues.
• Detailed case studies that feature a range of different types of childhood trauma. These case studies unfold in sections and are written to help learners understand what it is like to live through a traumatic experience and its aftermath from a child’s perspective. The variety of case studies available allows PBL facilitators to flexibly adapt the Core Curriculum for a broad range of different training-related audiences, needs, and settings.
• Instructional tools that facilitators can flexibly use as learning tools, or to assess learner progress, throughout the learning process.

For a more detailed overview and introduction to the Core Curriculum, click here . For answers to frequently asked questions about the Core Curriculum, click here . To access a series of online interactive lessons explaining the Core Concepts in greater detail, and other materials on the CCCT, visit the NCTSN Learning Center for Child and Adolescent Trauma . To access a Core Curriculum case vignette (Ella) that the Core Curriculum Interactive Learning Group adapted to teach learners how to use the 12 Core Concepts as lenses to critically reason through a case study, click here . 

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Introduction

Mike, a 35 year-old male, is presented to the emergency department with multiple puncture wounds to the right arm and bruising on the face. He arrived at the hospital via emergency medical services after calling 911.

Mike was playing with his dog, a German Shepherd, in front of his hoe one day when all of the sudden, his dog decides to bit his right arm and punch him in the face. He immediately takes off his jacket and notices blood all over his arm and calls 911. calling 911, Mike states that he has been bitten on his arm and punched in the face by his dog. The operator tells Mike that EMS will be there in 10 minutes and to clean the wounds with soap and water and to cover the wounds if possible.

On route to the hospital, EMS performs a primary assessment using the ABCDE approach.

• A irway: Patent
• B reathing: tachypneic with labored breath and breath sounds normal
• C irculation: pulses rapid and weak
• D isability (LOC): awake, alert, responds to pain and voice. GCS: 15
• E xposure: Site of wound exposed. Wounds on right arm and bruising on face noted

C-Spine Stabilization is not indicated.

Upon admission to the ED, the secondary assessment was performed. The patient’s vital signs were a BP: 92/54, HR: 120, RR: 22, T 100.7F, O2: 96% on room air, and a pain of 9/10. Performing a full head-to-toe assessment revealed:

• Neurological: Awake, alert and oriented x 4, GCS 15, full PERRLA
• Cardiovascular: Normal s1s2, pulses rapid and weak, cap refill <2 secs
• Respiratory: Tachypneic, labored breathing, normal breath sounds
• GI: Nondistended, soft, non-tender, bowel sounds active
• GU: No complaints of urinary problems
• Integumentary: Multiple right arm puncture wounds. Bruising on face. Site of wound warm and swollen. Skin is cool and pale.
• Musculoskeletal: weakness and pain in right arm
• Psychological: Possible PTSD

The patient’s medical history was gathered using the mnemonic device, AMPLE:

• A llergies: Latex
• M edications: Atorvastatin, metoprolol
• P ast medical history: Splenectomy 19 years ago
• L ast oral intake: a glass of water
• E vent leading to injury: playing with dog. Dog overexcited

Question 1: After reviewing the findings in the secondary assessment, what are some notable concerns to address in the assessment?

Question 2: Based on the secondary assessment, what interventions should the nurse expect to be ordered?

Question 3: After performing these interventions, should the patient be admitted into the hospital or discharged and given a follow up visit? Why?

Nursing Case Studies by and for Student Nurses Copyright © by jaimehannans is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License , except where otherwise noted.

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COMMUNITY CASE STUDY article

Community case study on trauma-specific treatment and counseling for refugee women exposed to intimate partner violence.

• 1 Psychotherapy and Psychosomatic Medicine, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
• 2 Department of Child Health, Norwegian Institute of Public Health, Oslo, Norway

Women experiencing intimate partner violence (IPV) are at high risk to suffer from severe mental health consequences, such as posttraumatic stress disorder (PTSD) and depression. Refugee women being exposed to IPV in the country of arrival are an especially vulnerable and understudied group and post migration persistent IPV should not be underestimated. Hence, research on special requirements regarding the treatment of these women is needed. We describe two individual cases from our work with refugee women suffering from PTSD symptoms who experienced IPV representing our trauma-specific therapeutic approach targeting this population. By analyzing their personal and medical history as well as their interactions with several institutions of the public sector and counseling centers, we illustrate the possibilities and limitations when helping our clients dealing with trauma-related mental health problems following the experience of IPV. Furthermore, we formulate general recommendations for providing adequate therapeutic frameworks concerning special requirements for the work with refugee women.

Introduction

Intimate partner violence (IPV) is defined as the experience of psychological, physical, and/or sexual abuse from current or previous male or female partners ( 1 ). Exposure to IPV is associated with an increased risk of developing mental health problems, including posttraumatic stress disorder (PTSD) and depression ( 2 – 4 ).

According to the World Health Organization (WHO) globally one in three women has experienced either physical and/or sexual violence, in most cases by an intimate partner. Available research indicates that immigrant and refugee women are especially vulnerable to IPV ( 5 , 6 ), as they are often exposed to established risk factors of IPV, such as originating from a community with broken social and protective networks, low levels of women’s access to paid employment, and dependencies on their intimate partners due to legal regulations ( 6 , 7 ).

However, trauma-specific treatment according to official guidelines and counseling for refugee women as victims of IPV involves special requirements, as this population might have particular problems, such as difficult housing circumstances and language barriers ( 8 – 10 ). These special requirements need to be pointed out and discussed in order to overcome social inequalities and barriers to health care for refugee women being exposed to IPV. Implementation of requirements is needed to improve the mental health of refugee women in general ( 11 ).

Background and Rationale

Our outpatient clinic for psychological trauma at the Dresden University Hospital Carl Gustav Carus is specialized in the treatment of PTSD and other trauma-related mental disorders. Most of our patients receive treatment paid for by their statutory health insurance and represent a population suffering from multiple mental health issues including dissociative or complex PTSD elements. If patients reach out to our facility shortly after being exposed to IPV or violent crimes in general, their treatment can also be paid for by public means for crime victims’ compensation. As IPV is considered to be a violent crime in Germany, victims are entitled to compensation under the Crime Victims’ Compensation Act ( 12 ). This includes up to 15 probationary sessions with a psychotherapist to provide fast access to the help system. If needed, further psychotherapeutic treatment can be provided by the services paid by the statutory health insurance.

Within the diverse population of our clinic’s patients, refugee women are a special group with specific needs. In recent years, the number of refugee women among our clients has been increasing, presenting us with the challenge to implement the common therapeutic approach in working with this population and meeting their special needs. Figure 1 provides an overview of our general therapeutic approach.

Figure 1 Topic areas and operators in the networking care for traumatized patients adapted from Reference ( 13 ).

Methodological Aspects

The data used for this article are derived from our internal clinic information system, where the clinic staff (psychologists, nurses, physicians, social workers) document every interaction with the patient as well as their observations. The authors contributed to collecting the data over the course of the treatment of the subjects in our facility. We obtained informed written consent from the patients authorizing the publication of their clinical cases.

Subjects and Methods

For this case report, we presented two complexly traumatized patients from our outpatient clinic whose mental health problems are typical for refugee women having been exposed to IPV in Germany (the country of arrival). Admission, diagnostic, and treatment processes were described, social and legal implications were listed for each case, results of each intervention that led to their current health improvement were described, challenges over the course of their treatments were also mentioned. By analyzing these factors of the therapeutic process, we showed what is needed to apply our general therapeutic approach for complexly traumatized patients to the special population of refugee women suffering from IPV in the country of arrival.

We aim to further the knowledge about the process of treatment and counseling of refugee women with PTSD and exposure to IPV. We want to present a strategy for other medical facilities offering treatment for the population of the study, hoping to contribute to overcome the barriers to access to health care services for these women.

In this article, we present two case reports. Both of the presented clients are diagnosed with PTSD following the exposure to severe IPV. They represent the challenges and enabling factors regarding treatment and counseling in this specific population. These challenges can be illustrated as depicted in Figure 2 .

Figure 2 Requirements for treatment and counseling for victims of IPV adapted from Reference ( 14 ).

The first patient is a woman from a country in the Middle East, who was 33 years old at the time of admission. We illustrate an overview of the challenges and enabling factors regarding treatment of this patient in Figure 3 . She was referred to our outpatient clinic for Psychotraumatology at the Dresden University Hospital by an outpatient clinic for refugees because of attempted suicide, intrusions, and nightmares. Besides, she had been suffering from epilepsy since her childhood. The patient reported to have been growing up in a violent family, being exposed to sexual and physical violence by her uncle and brother. When she could no longer bear the violence, she fled from the house and decided to escape her country of origin. On her way to Germany she fell into the hands of smugglers and decided to get married to protect herself from assaults by other men. The present relationship with her husband was violent as well. She reported not to be able to attend German language courses as she was anxious and therefore avoided leaving her apartment.

Figure 3 Requirements for treatment and counseling for victims of IPV adapted from Liang et al., 2005, presenting the case of Subject I ( 14 ).

Although suffering from mental health problems since her childhood, the patient never received psychiatric or psychotherapeutic treatment before. For epilepsy treatment she had been prescribed antiepileptics (Lamotrigin 200 mg 1–0–1 and Levetiracetam 500 mg 1–0–1).

In the mental health status examination, it was observed that the patient appeared suspicious und distanced. Intrusions existed as thoughts and flashbacks. She appeared to be emotionally unstable showing impulsive affect regulation. She seemed to be highly tensed and in an unhappy-dejected mood. At the time of the examination the patient sufficiently distanced herself from suicide. There was no indication of abusive consumption of addictive substances or addiction.

All criteria for Posttraumatic stress disorder (PTSD, ICD-10 F43.1) were met at this first clinical interview. Moreover, based on reported psychosocial and biographical details, Borderline personality disorder (ICD-10 F60.31) was suspected additionally to the previously diagnosed epilepsy (ICD-10 G40.9).

It took two years to establish a stable therapeutic relationship enabling the use of trauma-specific techniques according to guidelines. Crisis intervention and contact to specific counseling centers for IPV were at the center of the first therapy sessions because of the persistent IPV perpetrated by the husband. Effective cooperation with a local specialized counseling center for IPV was of invaluable help. We held several case conferences with their consultants to coordinate psychosocial help and to avoid double structures. As we were always dependent on the aid of an interpreter at our appointments, additional expenditure of time for organizational matters regarding the interpreter service was needed.

Over the course of the treatment, several therapy breaks occurred. Incidents like further IPV exercised by the husband or attempted suicide led to an admission at an inpatient department at a different hospital. During this period, antidepressant (Agomelatine) and mood-stabilizing neuroleptic (Quetiapine) medication was initiated. It often happened that the patient did not attend scheduled appointments without an excuse or that she was late. Hence, we set up a contract of punctuality, which led to higher reliability. During the course of the treatment at our clinic, the patient regularly consulted our clinic’s physician. Medication was adapted several times, as the former antidepressant medication had led to adverse side effects. Trimipramine was tolerated best.

During the individual psychotherapeutic therapy, we kept on exploring biographical details and helped the patient deal with current symptoms. We also focused on reflecting on her personality as we analyzed everyday life conflicts together. It continued to be difficult to focus on trauma therapy due to many organizational matters. The patient herself experienced frustration and anger, and often showed a demanding attitude towards other people.

For a longer period of time, the patient consulted our clinic’s social worker frequently as she had troubles finding a new apartment to finally be able to physically separate from her abusive husband, whom she described as controlling and aggressive. She and her violent partner were registered as a ‘community of dependence’, implying that they had to support each other financially. Furthermore, the patient sought help as her social benefits were cut, because she had not attended any integration course.

Two years after she first came to our facility she finally became financially independent from her partner. The groundwork has now been laid to apply trauma-specific treatment techniques in order to improve the patient’s quality of life.

Our second patient is a refugee woman from the North Caucasus region, who was 37 years old at the time of admission. We illustrate an overview of the challenges and enabling factors regarding treatment of this patient in Figure 4 . She reported having mental health problems following forced marriage at the age of 18 and abusive family relationships, but she never received treatment before. She had no previous history of medical conditions. The patient was referred to the outpatient clinic for psychological trauma at the Dresden University Hospital Carl Gustav Carus for the first time by her general practitioner (GP). At that time, she was living together with her violent and abusive husband and her six children. She was unintentionally pregnant and living in constant fear of her extremely violent husband, who was beating both her (also during her pregnancies) as well as their children.

Figure 4 Requirements for treatment and counseling preferences for victims of IPV adapted from Liang et al., 2005, presenting the case of Subject II ( 14 ).

She reported a long history of IPV including mental and physical violence as well as severe sexual violence since the beginning of the forced marriage to her husband. During her first pregnancy, she was beaten up by her husband so badly that she had to go to the hospital. However, her husband did not let her get medical treatment. During the time when she was pregnant with her sixth child her husband forced her to hand-dig a well in their garden at minus 10°C. She would always have to work, even at night, to earn money for the family. She told us that her partner would use that money to buy alcohol and drugs so that she and her children only had very little to eat. The patient tried to get separated from her husband in her country of origin. But because her children were then taken away from her and sent to members of her husband’s family she eventually came back to him. Because her husband got in trouble in their country of origin, he decided to take the family to Germany. She had to follow him, in the beginning with the hope that he would treat her better in Germany and stop consuming drugs. But his behavior did not change and she became pregnant again in Germany. In the fourth month of her last pregnancy her husband beat her up so badly that a social worker from another organization noticed it and helped reporting him to the police and referred her to a GP.

In the mental health status examination, the patient seemed to be very shy and tense. She reported symptoms of insomnia and chronic headaches as well as amnestic dissociative episodes. Intrusions existed as thoughts and flashbacks of IPV experiences; when she woke up after a nightmare she felt the pain physically. Her mood was depressed, she showed low motivation on the one hand, and seemed to be highly tensed regarding psychomotoric functioning on the other. She reported sometimes having suicidal thoughts but being able to distance herself from those thoughts sufficiently. There was no indication of abusive consumption of addictive substances or addiction.

As a result of the mental health status examination, we diagnosed her with severe Major Depressive Disorder (ICD-10 F32.1) and PTSD (ICD-10 F43.1) with dissociative and complex symptomatology; both diagnoses were not related to the pregnancy (Z34.8). Mixed dissociative disorder (ICD-10 F44.7) and pain disorder exclusively related to psychological factors (ICD-10 F45.41) were diagnosed additionally as these symptoms were persistent two years after birth of the seventh child.

As she was pregnant, when she first came to our clinic, we decided to offer her crisis intervention, including psychoeducation and low-dose antidepressants in order to improve sleep quality (Amitriptylin 25 mg 0–0–0–1/2). Intense social care in parallel with specific IPV counseling helped her separate from her partner, with the arrangement of the divorce, finding a new apartment, and other organizational matters. The youth welfare center was involved as the children had to be protected. A restraining order against the husband was imposed. The parental rights of the ex-partner were terminated, only accompanied contact between father and children was allowed. Still he threatened her several times, saying that he would kill her or take away her children.

After giving birth to her seventh child, trauma-specific psychotherapy was paused for almost two years. As PTSD and dissociative symptoms persisted for those two years, trauma-specific psychotherapy was continued. Besides enhancing her understanding of anamnestic and biographical details as well as working with defining the trauma focus, resource oriented techniques for dealing with the dissociative and somatic symptoms were installed. Sometimes longer therapy breaks occurred as one of the patient’s children became severely sick. The patient reported feeling socially ostracized as the community of people from her country of origin would judge her for leaving her husband and not wearing a hijab anymore. The paternal side of her family would be judging her for ‘leaving her family’ and said that she was the ‘black sheep of the family that has to go away’. Therefore, the patient reported to be very scared of going back to her country of origin.

During the group therapy the patient had the opportunity to learn to use relaxation techniques as well as to benefit from the exchange with others and learn from their experiences. The patient reported this to be very helpful and was open to join other participants of the group therapy for social events outside the therapy setting. Still, she remained in great need of further guideline based trauma-specific treatment.

We presented the cases of two refugee women suffering from PTSD after being exposed to IPV. Both of the cases were managed with pharmacotherapy, psychotherapeutic sessions (in one case also group therapy interventions), and counseling with social workers. Both patients showed typical patterns of refugee women with PTSD caused by IPV experiences.

As the analysis of the treatment and counseling requirements showed, the predisposing variables for both subjects are adverse. On admission, both patients suffered from persistent stress exposure, limited enabling resources, and adverse physical and mental health conditions. Both patients were multi-morbid regarding their mental health condition. It is for these reasons, that both subjects needed a lot of support not only from Physicians and psychotherapists but also from social workers and interpreters. Before we could begin with a trauma-specific psychotherapy we provided stabilizing psychotherapy and put a lot of effort to build a stable relationship with the patients, which led to an additional expenditure of time compared to therapeutic processes with other populations.

As we pointed out in our results section, there are special requirements for the treatment of refugee women with complex history of trauma including exposure to IPV. In the following, we want to discuss two of the aspects that we find most important regarding an adequate psychotherapeutic and counseling approach.

Need for Perseverance

As our case reports show, the treatment and counseling of women suffering from mental health problems following IPV require a remarkably large amount of additional expenditure of time, which is confirmed by other studies regarding refugee mental health ( 15 ). Persistent violence is an enormous obstacle to the application of trauma-focused therapy. In the presented cases several years of resource oriented therapy and support by social workers were needed as trauma-specific treatment approaches were not feasible at that time ( 8 ). It is important to point out that this may cause frustration in the clinicians, and in the women, too; as it might appear that there is no progress at all, e.g., the process of terminating the relationship with a violent partner is often complicated and dangerous ( 16 , 17 ). It is especially difficult for refugee women, due to financial and legal limitations. Parental responsibility for joint children is also a factor that increases the likelihood of continuing victimization, even if restraining orders are imposed ( 17 ). It is very important for clinicians to be aware of the women’s emotional distress relating to termination of a violent relationship. Furthermore, affected women often report experiencing a lack of support from their families and their social environment ( 18 ), which is confirmed by our examples. As seen in Subject I, women who grew up in a violent home are more likely to become victims of IPV, too ( 19 ).

In the presented cases, both women suffered from mental health problems after having been exposed to severe IPV. However, IPV is not the only form of violence most of these patients have experienced. Women fleeing from their country of origin are very likely to experience physical and/or sexual assault during their flight ( 20 , 21 ). This can also be seen in the case of Subject I, who married somebody just to protect herself from assaults from other men. Such exposure to violence makes the diagnostic process more complex and requires more demanding therapy. A complex trauma history can also lead to attachment disorders, the patients then have difficulties in building stable relationships, also with the clinicians.

During the often prolonged course of therapy clinicians need the opportunity to reflect on the therapeutic process, e.g., in regular case conferences, and remind each other that it is normal that treatment in these cases may take a long time. Recent research and our experience shows that a combination of a variety of therapeutic interventions and counseling is needed to meet the requirements of these complex cases ( 22 ).

Extensive Aid Network

As there are usually several institutions involved in helping the victims of IPV, it is important to be informed about each other’s interventions ( 23 ). With the consent of our patients we regularly hold case conferences with counseling centers, external social workers etc.

We found that the ongoing support from social services is extremely important for refugee women experiencing or having experienced IPV. First, there are many challenging organizational matters that not only the women are unable to solve alone (due to their mental health problems or language barriers), but that also represent barriers for starting trauma-specific treatment. In both of the presented cases the women needed a lot of support from the social workers to get separated from their violent partners, get legal arrangements, and to become financially independent as well as to get the opportunity to live separately from their abusive partner. Moreover, additional support by social services, as well as stable work and living conditions are highly correlated with decreased reports of chronic pain ( 24 ).

When working with mentally ill refugee women, aid from an interpreter is usually needed ( 25 ). In Germany, however, interpreter-aided therapy is not available for everyone. If the asylum proceedings are still pending or if the women are recognized refugees, interpreter-aided therapy can usually proceed. If their status is unclear, e.g., they are granted subsidiary protection, interpreters can only be paid privately. In conclusion, there is a group of refugee women, who do not have access to interpreter-aided therapy. In addition, it is time consuming for the clinic’s staff to organize interpreters for every appointment, even if the service is covered financially. The therapeutic success of the therapy also depends on the relationship not only between therapist and patient, but also between patient and interpreter.

Since we only presented two cases of a wider population and against the background of a lack of studies on this vulnerable group, caution is needed when generalizing our results. Researchers’ own subjective feelings may influence the reporting of the case study (researcher bias). We found that our patients suffered from multi-morbidities, however such multi-morbidities make causal claims difficult, i.e., claiming PTSD symptoms to be a direct consequence of IPV ( 26 , 27 ). However, it is important to mention that dealing with multi-morbidities and PTSD reflects the everyday reality of outpatient clinics for psychological trauma.

The studies that do exist in connection with psychotherapeutic support for refugees show the importance of appropriate housing and access to specialized help and counseling networks with low barriers to entry, as well as broader social integration. Caretakers for refugees should be flexible and well-trained in trauma-informed care, but also attentive to the need for stable material living conditions, as mediated by social services ( 11 , 28 , 29 ). All of this equates to a significantly higher investment of resources, for psychotherapy to be applied with any measure of success.

Through our own professional experience, we have come to an understanding that even more resources than usually available are required to provide extensive support of social workers and interpreters in facilities giving treatment to refugee women with PTSD and exposure to IPV. Abusive relationships are often persistent even over the course of therapy and the patients need a lot of support for leaving the partner perpetrating IPV. The lack of these services might be a barrier to access to health services those women need urgently and to provide PTSD treatment according to guidelines. Furthermore, future studies of this particular population are necessary to gain deeper knowledge of the special requirements for the therapy of PTSD in these women in order to improve their quality of life.

As has been shown in both individual cases, patients of this population are often characterized by multi-morbidities and require long-term multi-professional care.

We demonstrated that the general psychotherapeutic approach for the treatment of PTSD can be applied to refugee women with PTSD and exposure to IPV. However, it became clear that the therapeutic approach needs to be adjusted to the special needs of this population.

In the future, further studies are needed in order to better explore and understand the dynamics of IPV in this population and to tackle/reduce its specific consequences on refugee women.

Data Availability Statement

The datasets generated for this study are available on request to the corresponding author.

Ethics Statement

Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

Author Contributions

AP, SG-N and JS contributed to the conception as well as the design of this article and did the literature search. AM gave methodological advice. CV, UR, and WK were involved with counseling and treating the subjects of the case reports. CV contacted and asked them to allow us to use their stories. UR and WK reported their therapeutic experience with the subjects. AP extracted and synthesized the data from the medical reports and wrote the first draft of the manuscript. JS contributed her expertise as a physician specialized in trauma related mental health problems. All authors contributed to manuscript revision, read, and approved the submitted version.

The primary author is related to the project ‘Kompetenzzentrum Traumaambulanzen in Sachsen’ (center of excellence for the treatment of psychological trauma in outpatient clinics in Saxony). Grant by the federal state of Saxony.

We acknowledge support by the open access publication funds of the SLUN/TU Dresden.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments

We would like to thank our patients for giving us the opportunity to describe their individual stories in this article. Especially as we know that both are still suffering from the consequences of their history of IPV, we are grateful for their courage and willingness to publish their case reports.

1. Breiding M, Basile KC, Smith SG, Black MC, Mahendra RR. Intimate partner violence surveillance: Uniform definitions and recommended data elements. Version 2.0. (2015).

Google Scholar

2. World Health Organization. Global plan of action to strengthen the role of the health system within a national multisectoral response to address interpersonal violence, in particular against women and girls, and against children. (2016).

3. Ellsberg M, Jansen HAFM, Heise L, Watts CH, Garcia-Moreno C. Intimate partner violence and women’s physical and mental health in the WHO multi-country study on women’s health and domestic violence: an observational study. Lancet (2008) 371(9619):1165–2. doi: 10.1016/S0140-6736(08)60522-X

PubMed Abstract | CrossRef Full Text | Google Scholar

4. Ferrari G, et al. Domestic violence and mental health: a cross-sectional survey of women seeking help from domestic violence support services. Global Health Action (2016) 9(1):29890. doi: 10.3402/gha.v9.29890

5. De Schrijver L, Vander Beken T, Krahé B, Keygnaert I. Prevalence of sexual violence in migrants, applicants for international protection, and refugees in Europe: a critical interpretive synthesis of the evidence. Int J Environ Res Public Health (2018) 15(9):1979. doi: 10.3390/ijerph15091979

CrossRef Full Text | Google Scholar

6. World Health Organization. Displaced or refugee women are at increased risk of violence. What can WHO do?(2018). Available from: https://www.who.int/reproductivehealth/displaced-refugee-women-violence-risk/en/ .

7. World Health Organization. Violence against women. Key facts. (2017).

8. Zehetmair C, Tegeler I, Kaufmann C, Klippel A, Reddemann L, Junne F, et al. Stabilizing techniques and guided imagery for traumatized male refugees in a german state registration and reception center: a qualitative study on a psychotherapeutic group intervention. J Clin Med (2019) 8(6):894. doi: 10.3390/jcm8060894

9. Böttche M, Stammel N, Knaevelsrud C. Psychotherapeutic treatment of traumatized refugees in Germany. Der Nervenarzt (2016) 87(11):1136–3. doi: 10.1007/s00115-016-0214-x

10. Erim Y, Morawa E. Psychotherapy with immigrants and traumatized refugees. Psychotherapie Psychosomatik medizinische Psychol (2016) 66(9-10):397–9. doi: 10.1055/s-0042-115412

11. Priebe S, Giacco D, El-Nagib R. Public health aspects of mental health among migrants and refugees: a review of the evidence on mental health care for refugees, asylum seekers and irregular migrants in the WHO European Region: World Health Organization. Regional Office for Europe. (2016).

12. Federal Ministry of Labour and Social Affairs. Compensation and assistance for victims of violent crime. (2016). Available from: https://www.bmas.de/EN/Our-Topics/Social-Security/compensation-and-assistance-for-victims-of-violent-crime.html .

13. Epple F, Weidner K, Schellong J. Praxisbuch Psychotraumatologie: Georg Thieme Verlag. (2018).

14. Liang B, Goodman L, Tummala-Narra P, Weintraub S. A theoretical framework for understanding help-seeking processes among survivors of intimate partner violence. Am J Community Psychol (2005) 36(1-2):71–4. doi: 10.1007/s10464-005-6233-6

15. Böttche M, Heeke C, Knaevelsrud C. Sequential traumatization, trauma-related disorders and psychotherapeutic approaches in war-traumatized adult refugees and asylum seekers in Germany. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz (2016) 59(5):621–6. doi: 10.1007/s00103-016-2337-4

16. Rhatigan DL, Street AE, Axsom DK. A critical review of theories to explain violent relationship termination: implications for research and intervention. Clin Psychol Rev (2006) 26(3):321–5. doi: 10.1016/j.cpr.2005.09.002

17. Anderson DK, Saunders DG. Leaving an abusive partner: an empirical review of predictors, the process of leaving, and psychological well-being. Trauma Violence Abuse (2003) 4(2):163–1. doi: 10.1177/1524838002250769

18. Wachter K, Cook Heffron L, Dalpe J. “Back home you just go talk to the family”: the role of family among women who seek help for intimate partner violence pre- and postresettlement to the United States. J Interpers Violence (2019). doi: 10.1177/0886260519835861

19. McKinney CM, Caetano R, Ramisetty-Mikler S, Nelson S. Childhood family violence and perpetration and victimization of intimate partner violence: findings from a national population-based study of couples. Ann Epidemiol (2009) 19(1):25–2. doi: 10.1016/j.annepidem.2008.08.008

20. Napolitano F, Gualdieri L, Santagati G, Angelillo IF. Violence experience among immigrants and refugees: a cross-sectional study in Italy. BioMed Res Int (2018) 2018. doi: 10.1155/2018/7949483

21. Korac M. War, flight, and exile: Gendered violence among refugee women from post-Yugoslav states . Berkeley: University of California Press (2004). doi: 10.1525/california/9780520230729.003.0012

22. Rivas C, Vigurs C. A realist review of which advocacy interventions work for which abused women under what circumstances: an exemplar. Cochrane Database Systematic Rev (2018) (9). doi: 10.1002/14651858.CD013135

23. Schellong J, Epple F, Weidner K, Möllering A, Models of mental health care for vulnerable refugees in the community. Psychotherapie Psychosomatik medizinische Psychol (2017) 67(3-04):134–1. doi: 10.1055/s-0042-116080

24. Kashyap S, Page AC, Joscelyne A. Post-migration treatment targets associated with reductions in depression and PTSD among survivors of torture seeking asylum in the USA. Psychiatry Res (2019) 271:565–2. doi: 10.1016/j.psychres.2018.12.047

25. Brandl EJ, Schreiter S, Schouler-Ocak M. Are Trained Medical Interpreters Worth the Cost? A Review of the Current Literature on Cost and Cost-Effectiveness. J immigrant minority Health (2019) 1, 1–7. doi: 10.1007/s10903-019-00915-4

26. Bollen KA. Causality and causal models . Structural Equations with latent variables. New Jersey (1989) p. 40–79. doi: 10.1002/9781118619179.ch3

27. Cicchetti D, Rogosch FA. Equifinality and multifinality in developmental psychopathology. Dev Psychopathol (1996) 8(4):597–0. doi: 10.1017/S0954579400007318

28. Schick M, Morina N, Mistridis P, Schnyder U, Bryant RA, Nickerson A. Changes in post-migration living difficulties predict treatment outcome in traumatized refugees. Front In Psychiatry (2018) 9:476. doi: 10.3389/fpsyt.2018.00476

29. Bakker L, Dagevos J, Engbersen G. The importance of resources and security in the socio-economic integration of refugees. A study on the impact of length of stay in asylum accommodation and residence status on socio-economic integration for the four largest refugee groups in the Netherlands. J Int Migration Integration (2014) 15(3):431–8. doi: 10.1007/s12134-013-0296-2

Keywords: mental health, refugee women, intimate partner violence, posttraumatic stress disorder, trauma-specific psychotherapy, aid network, counseling, post migration

Citation: Pogarell A, Garthus-Niegel S, Mojahed A, von Verschuer C, Rokyta U, Kummer W and Schellong J (2019) Community Case Study on Trauma-Specific Treatment and Counseling for Refugee Women Exposed to Intimate Partner Violence. Front. Psychiatry 10:891. doi: 10.3389/fpsyt.2019.00891

Received: 17 July 2019; Accepted: 12 November 2019; Published: 05 December 2019.

Reviewed by:

Copyright © 2019 Pogarell, Garthus-Niegel, Mojahed, von Verschuer, Rokyta, Kummer and Schellong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Anneke Pogarell, [email protected]

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

The long-term consequences of early childhood trauma: a case study and discussion

Affiliation.

• 1 John Jay College of Criminal Justice (CUNY) in New York, NY 10019, USA. [email protected]
• PMID: 17326730
• DOI: 10.1521/psyc.2006.69.4.362

There is a great need to better understand the impact of traumatic events very early in life on the course of children's future development. This report focuses on the intriguing case of a girl who witnessed the murder of her mother by her father at the age of 19 months and seemed to have no recollection of this incident until the age of 11, when she began to exhibit severe symptoms of posttraumatic stress disorder (PTSD) in response to a traumatic reminder. The case presentation serves as the basis for a discussion regarding pertinent issues involved in early childhood trauma. This case and accompanying discussion were originally presented at the 19th Annual Meeting of the International Society for Traumatic Stress Studies and were transcribed and revised for use in this article. Specific topics include early childhood memory and trauma, learning and the appraisal of danger, and PTSD and traumatic grief in early childhood. Clinical and public health implications are also discussed. This case illustrates the dramatic impact that "preverbal" traumatic memories can have on children's later functioning and speaks to the importance of assisting very young children in the immediate aftermath of traumatic events.

Publication types

• Case Reports
• Adaptation, Psychological
• Child, Preschool
• Cognitive Behavioral Therapy
• Combined Modality Therapy
• Diagnosis, Differential
• Dissociative Disorders / diagnosis
• Dissociative Disorders / psychology
• Family Therapy
• Follow-Up Studies
• Homicide / psychology*
• Life Change Events*
• Maternal Deprivation*
• Mental Recall
• Personality Assessment
• Personality Development*
• Repression, Psychology
• Spouse Abuse / psychology*
• Stress Disorders, Post-Traumatic / diagnosis*
• Stress Disorders, Post-Traumatic / psychology

The patient was intubated by EMS and brought by helicopter to your level 1 trauma center. A foley catheter is placed. She’s had  CT of her head, neck, chest and pelvis. Her initial assessment reveals the following:

• GCS 6 (No eye opening, no speech, withdraws to painful stimuli)
• Gross hematuria noted in urine drainage bag
• Profuse bleeding from head and open right tib/fib fracture

The patient is taken to emergency surgery for a decompressive craniotomy with bone flap, EVD placement and exploratory laparotomy with bladder repair. She is then brought to you in the surgical ICU. What do you expect to see and do for this patient? Let’s use LATTE!  If you don’t know what LATTE is, check it out here!

L = LOOK: After a decompressive craniotomy with a flap, your patient will have a large gauze dressing on her head. In this case she also has an EVD (extraventricular drain). She will be on a ventilator because her GCS is still 6. And, due to the exploratory laparotomy, she’ll also have an abdominal dressing and possibly a drain. If C-spine is involved, she’ll be wearing a collar, but our gal’s C-spine was cleared…yay!

A = ASSESS:  The main assessments you will be doing on this patient are neurological and hemodynamics. What is she doing neurologically? What is her GCS? Are her pupils equal? Are there signs of shock? Is she bleeding anywhere? And, because she’s vented, you’ll be keeping an eye on her respiratory status as well…is she compliant with the vent? How do her lungs sound? What’s her O2 saturation? Is she breathing spontaneously? What kind of tidal volumes are we getting?

T = TESTS: You’ll do an ABG at some point to make sure she’s being ventilated adequately. You’ll also want to keep a close eye on CBC and coags as you monitor for bleeding and infection. Other labs include a chem panel to keep those electrolytes optimized! Expect to be taking this patient to CT a few times to keep an eye on the bleeding into her brain and any hydrocephalus that may be present. She’ll get a chest X-Ray daily since she’s on a vent and has rib/clavicle fractures. She may also get cystogram studies to keep an eye on how her bladder is doing. Remember she had hematuria…so they’ll want to keep a close eye on that.

T = TREATMENTS: How will this patient be treated? If you read my book, Nursing School Thrive Guide, you’ll recall that I talk quite a bit about prioritizing continuously. The treatments you provide at 0300 could be vastly different from the treatments you’re providing at 0600, based on the patient’s condition. For a fresh post-op patient who’s had a decompressive craniotomy many of your treatments/interventions are going to be focused on keeping the ICP within normal limits. You’ll also be administering pain and sedation meds as well as antibiotics. Depending on blood loss, you may be giving packed red blood cells. Note that we haven’t fixed her open fracture yet…that has to wait until morning when the ortho doc can get to her. So for now we’re just adding additional dressings to the site and keeping an eye on bleeding.

E = EDUCATION: At this point, you’re not providing education to the patient with a GCS of 6. However, you will be educating the family. In this acute phase, you don’t want to overwhelm them with information…it’s going to go in one ear and out the other. The highlights to hit on include: ICP management, pain control and sedation.

It is now 0430 and your monitor alarm starts going off for elevated ICP. It’s 23. Whatcha gonna do? (For a refresher on ICP management, check out this post here!)

First things first…assess your patient, not the monitor. You enter the room and do a quick assessment…this is what you find: head crooked off to one side, knees gatched, temp elevated, tachypnea and dyssynchrony with the ventilator, no drainage since you last drained the EVD an hour ago. Hmmm….what’s wrong with this picture?

Step 1: Straighten the patient’s neck to allow CSF to drain more freely. Step 2: Un-gatch the knees to reduce intrathoracic pressure Step 3: Looks like she might be fighting the vent…increase sedation and pain medication Step 4: Check EVD…make sure there are no kinks in the tubing. In most facilities, policy states that you can BRIEFLY drop the level of the drainage bag to ensure patency…you do this and note drainage in the bag…so there are no kinks or clots. Hmmm… Step 5: Initiate cooling measures…IV Tylenol works great as do ice packs. Be careful of shivering, though! Shivering increases ICP. Step 6: Give it a few minutes and re-assess.

Thankfully the rest of your shift goes smoothly. You report off to Super Nurse, RN and head home for a day of blissful sleep. When you come back in that evening, this is what you hear in report:

• Pt went to surgery at 1000 that morning for ORIF of the right tib/fib fracture, right ulnar/radial fracture and right femur fracture.
• Hgb dropped from 8.5 to 7.2…you are now doing serial Hgb and Hct every six hours. Your next draw is due at 2200.
• Temp spiked to 39.1, cultures drawn, antibiotics continued.
• ICPs still hovering around 18-20. Neurosurgeon changed the height of the EVD from 10mm Hg to 5mm Hg…EVD drainage has been steady at 10ml/hr throughout shift.
• GCS remains at 6.
• Pt still on ventilator.
• Plan is for pt to have pelvic fracture fixed the next day.

Upon your initial assessment you note the following:

• BP lower than it was last night…hovering around 95 systolic.
• O2 sats a bit lower than the night before. They were 98% then, they’re 93-95% now.
• Temp is better…that’s good!
• Lung sounds are mildly coarse.
• ICP 19-20. EVD drainage is good and she’s adequately sedated.

An hour later, you’re at the nurse’s station doing an ungodly amount of charting, when your monitor alarm goes off. ICP is 22. You do all your checks…positioning, temp, EVD patency…all looks good. But her ICPs are still high. As you are doing your assessment, the ICP creeps up to 23-24. Time to notify the neurosurgeon on call.

SBAR Communication

“This is Nurse Sam, calling about your patient Ramirez in Trauma ICU bed 10. She had a decompressive craniotomy yesterday. Her ICPs are holding steady in the 23-24 range. She’s afebrile, well-sedated, compliant with vent. GCS remains at 6 and EVD drainage is averaging about 10ml/hr. What do you think about trying mannitol?”

So, your neurosurgeon thinks this is a fantastic idea and orders Mannitol q 4 hr prn ICP > 20; Check serum sodium prior to each dose; Hold for serum sodium > 146. You give your first dose and watch the monitor as the ICP drops down bit by bit to a more acceptable 14. Go you!

A few hours hours later, at 2230, you notice your patient’s O2 sats have dropped dramatically…they’re now 74%. What the heck? You hustle into the room and amp up the ventilator to give 100% FiO2. As you place your stethoscope into your ears, you quickly assess the ET tube to ensure it hasn’t become dislodged. You listen to her lungs and hear no lung sounds on the right…the same site as her rib fractures and lung contusion. You call for help and immediately take her off the vent and manually breathe for her using the BVM. When your nurse friends show up, you ask one to call RT, one to call the doc and another to put in an order for a stat Chest X-RAY. What is going on?

As you are bagging the patient, waiting for the RT to show up and take over, you notice tracheal deviation off to the left and BP has dropped to 83/54. You relay this to the nurse who is on the phone with the MD, stressing that she needs to get up there STAT! Your patient has a pneumothorax and seconds count. The respiratory therapist arrives to take over the airway and you ask one of your friends to obtain a large-bore needle.  You ask another to grab a chest tube kit…it’s time to get serious folks.

The MD arrives, agrees with your assessment of tension pneumothorax and, using the large-bore needle, performs an emergent pleural decompression. You watch in amazement as the patient’s O2 saturation levels quickly start to climb back to 93%. You prep the pleuravac and monitor the patient while the MD inserts a chest tube on the right side. Good catch!

While you have the doc there, you notify her that the 2200 H&H showed a hemoglobin of 6.9. She orders 2 units packed red cells. You give the blood and, happily, the patient’s O2 saturation and blood pressure both improve. And, with a couple of Mannitol doses your patient’s ICP hangs around 14 for the rest of the night. Nice job…you go home and sleep a beautiful sleep.

When you come on that night, the off-going nurse reports the following:

• Your patient had her pelvic fractures repaired that day, returning from surgery at 1120 with hemovac drain at surgical site.
• The tachycardia that has been present since admission has slowed to normal sinus rhythm, likely due to decreased pain now that all her fractures are repaired.
• Urine output averaging 75ml/hr.
• The biggest news is that her GCS has improved dramatically…she’s now a 9 (opens eyes to speech (3 points), no verbal response due to ETT (1 point) and localizes to pain (5 points). This is a massive improvement! Guess she likes that EVD and all that lovely Mannitol.
• The plan is to let her rest overnight, and lighten up her sedation early in the morning with the neurosurgeon rounds.

Your initial assessment reveals the following:

• ICP 11 (yay!) with 5ml CSF from last hour…looks like drainage is slowing down.
• BP 129/67; HR 85
• Surgical dressing across abdomen and at right hip. Both are clean, dry, intact. Belly is soft, flat; pt grimaces and moves hands toward abdomen as you palpate…likely very tender.
• All other dressings from prior surgeries also clean, dry, intact.
• Lung sounds equal bilaterally; chest tube is patent; O2 saturation 98% on 30% FiO2.
• GCS remains at 9…she is slowly but steadily improving. Whew!

At 2300, you notice that your patient’s  blood pressure is trending down and heart rate is trending up. You aren’t alarmed yet…though you are keeping a careful eye on things. Currently, her O2 saturation is 94%, BP is 109/63, HR is 104, urine output 45/hr. Nothing scary yet, but you don’t like how the trend is going. An hour later, at 0000 you notice O2 sat is now 92 %, BP is 98/62, HR is 115 and urine output for the past hour is 25. You definitely don’t like how this is going. At all. You perform your midnight assessment and notice that your hemovac is full…it was empty two hours ago…what’s going on? You drain the hemovac and pull back the patient’s gown. You immediately see that her belly isn’t quite as flat…and when you touch it it feels much more firm. You immediately go call the ortho surgeon…you’re getting pretty good at waking docs up in the middle of the night, so this SBAR should be a no-brainer!

“This is Nurse Sam, calling about your patient Ramirez in Trauma ICU bed 10. You performed an ORIF on her pelvis today and I’m concerned she may be bleeding into the abdomen. BP has dropped 30 points since 1900, most of the past hour. HR is up from 85 to 115, O2 sats are down to 91 from 98, and urine output is decreasing. Her belly is a bit rounded and more firm than on my initial assessment. I’d like to get a stat Abdominal scan, a stat CBC and coags, and ask you to come see this patient.”

The ortho surgeon agrees with your order requests and states she is going to call the general surgeon who is on site at the hospital right now. If the patient is bleeding, she’s going to need to go to surgery asap. You anticipate this happening, so you get ready:

• You assign a friend to draw a rainbow (this means you’re going to draw the three main studies…a chemistry panel, a CBC and a coagulation panel…these are in different colored tubes so we call it a “rainbow”).
• Another nurse calls blood bank to ensure the patient has units on hold and also calls CT to tell them they’ve got a stat patient coming in.
• You call RT so they can come put the patient on the portable ventilator.
• You get the patient packed up and ready to transport to CT. They quickly run the scan and a few minutes after you return to the room the general surgeon shows up. She assesses the patient, agrees with your findings, and logs into the computer to view the scan which has miraculously been processed amazingly fast! She notes blood in the abdominal space and says what you’ve been anticipating for the past hour…”We’re going to surgery.”
• You wheel the patient down to surgery, report off to the circulating RN and anesthesiologist and decide this is a perfect time for your lunch break.  Nice work,  you!

The patient comes back from the OR 90 minutes later. The surgeon tells you she’d had a large hematoma in one of her pelvic vessels that ultimately burst, causing the drop in pressure and distended abdomen. The patient received four units packed red blood cells in the OR and you’re back to doing q 6-hr H & Hs. BP has improved to 115/67, HR Is 94 and O2 saturation is 98%. That was a close one! Thankfully, the rest of your night goes off without a hitch. When the neurosurgeon rounds at 0600, you’ve had sedation off for about 20 minutes. The patient is moving much more and opening eyes spontaneously. She is not, however, following commands…but her total GCS is now 10. The neurosurgeon likes what he sees and states that if she continues to improve she could likely be weaned from the ventilator soon.

Your relief arrives right on time, you report off and tell her you’re back again that night for your fourth shift in a row. You feel like this patient has really put you through the wringer and hope your last night of the week is easier than the last three! Off you go to sleep.

When you arrive that night, you receive the following information in report:

• GCS is now 11…patient is following commands and trying to write notes! Sedation is minimal.
• Pt has been on CPAP for the past three hours and doing great with RR 14-22 and O2 saturation levels > 95%. She’s pulling good tidal volumes and on a measly 30% FiO2. Awesome!
• ICP has been 4-8 all day with minimal drainage from EVD.
• The PM doc is planning to be by around 2000 to assess pt. You are to have an ABG done at that time to assess for readiness to extubate. You cross your fingers!
• All other VS stable, all dressings CDI and hemovac draining an appropriate amount of serosanguinous fluid.

When the doc comes by at 2000,  you’ve got sedation completely off and your ABG done. After a review of that morning’s CXR and a glance at your patient’s fantastic ABG results, the MD decides to write an order to extubate. Finally some real progress!

You contact your respiratory therapist, grab a towel and a 12 ml syringe. You suction the patient’s mouth and oropharynx thoroughly, making sure you get all the secretions cleared from above the ET cuff. The RT loosens the ET holder from the patient’s face while you get the nasal cannula ready to go with 2L O2. The RT then deflates the cough, tells the patient to cough and pulls the tube. You place the nasal cannula on the patient and instruct her not to talk for a little while. You encourage her to take slow, deep breaths through her nose and cough periodically to keep her lungs clear. Her O2 saturation is 99% and when you ask her how she’s doing she gives you a thumbs up to indicate she is doing fine. You did it!

Now that you’ve got an awake pt who could potentially  move around a lot in bed, you need to be extra careful you don’t over drain through the EVD. You explain to the patient (and the patient’s family) that she is not to abruptly change position or move the head of the bed. She nods to indicate understanding and then mouths the words, “What happened?” You give her a brief synopsis…something along the lines of,

“You were in an accident four days ago and badly injured. You’ve had several surgeries for a head injury and broken bones. You currently have a drain in your head to keep the swelling in your brain under control. You also have a chest tube in place to keep your lungs expanding normally. You also have a catheter in your bladder draining urine. Currently everything looks good. Your vital signs are stable and your neuro status is improving. The short term plan is to keep your pain controlled and monitor your neuro status throughout the night. To do that I’ll have to wake you every couple of hours. Do you understand? Now, I know this is a lot to take in and I want you to try not to worry…that’s my job. I’ll be right out there all night and I’m watching over you continuously. You are hooked up to monitors that may occasionally make noise…a lot of times those noises are false alarms and nothing to be concerned about so try not to let it upset you. As long as I’m not alarmed, you don’t need to be alarmed. OK? Now, what is your pain level on a 0-10 scale?”

Throughout the rest of the night, you’re on dilaudid duty and neuro-assessment duty. The patient is scoring a 14 by the time morning rolls around and you report off to the oncoming nurse feeling like you’ve done an awesome job these past four nights. You rock!

I hope you enjoyed this scenario-based look at caring for a post-surgical trauma patient. Luckily I haven’t had a patient with this many complications, but the point is you are always on the lookout for what COULD go wrong. Being ready when the shizzle hits the fan can mean the difference between life and death…but you’re an awesome nurse and you got this!

Note I couldn’t cover every contingency, assessment, treatment, med and diagnostic test in this one case study…this is just an example and I sincerely hope it helped paint a picture for you! Got a story to share about how you caught a problem before it got too big? Got questions about post-op care? Let’s talk about it in our Facebook Group, Thriving Nursing Students .

____________________________________________________________

The information, including but not limited to, audio, video, text, and graphics contained on this website are for educational purposes only. No content on this website is intended to guide nursing practice and does not supersede any individual healthcare provider’s scope of practice or any nursing school curriculum. Additionally, no content on this website is intended to be a substitute for professional medical advice, diagnosis or treatment.

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The Trauma-Informed Coach: Strategies to support clients when their past prevents progress

In this highly practical guide, Joanna Harper shares her experience and expert knowledge to equip you with the crucial awareness and skills you need...

By Joanna Harper

RRP: £19.99

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As a coach or practitioner your focus is always on facilitating your clients to flourish, thrive and believe in their potential.

But what happens when past traumas and emotional injuries prevent them from making progress in the here and now? How do you respond?

In this indispensable and highly practical guide, master coach Joanna Harper shares her experience and expert knowledge to equip you with the crucial awareness and skills you need to competently manage even the most challenging of client situation and experiences.

Through ten essential core competencies, five unique, powerful, and practical models, plus an illuminating and insightful range of case studies that bring everything to life, you’ll discover how to:

• Put trauma awareness at the core of your coaching practice
• Feel confident that you’re dealing with trauma supportively
• Handle the distressing emotions and painful memories that past traumas can surface
• Know when to refer clients to other services or professionals
• Focus and draw on your client’s existing resources and strengths

Whether you’re newly certified or already an experience coach or practitioner, by being trauma-informed and in possession of these forward-thinking, empowering skills, you’ll always know the most appropriate measures and suitable ways to advance when past experiences are preventing you client’s progress.

"The Trauma Informed Coach" Strategies to support clients when their past prevents progess. By Joanna Harper

In "The Trauma Informed Coach", Joanna Harper offers a vital resource for coaches and practitioners supporting clients with past traumas. This book is an essential addition to any coaching library, providing a comprehensive framework and practical insights that can deeply impact coaching sessions. Harper stresses the importance of creating a safe, non-judgmental space for clients to share their experiences, emphasising empathy and validation to build trust and rapport. A standout feature is the focus on trauma awareness, highlighting the need to understand how trauma affects both mind and body. Harper guides readers in recognising trauma signs, ensuring coaches can provide sensitive, informed care. The book expertly addresses boundaries, crucial in coaching, and underscores the importance of respecting both the coach's and client's boundaries, especially with trauma survivors. Harper explores trigger management and the coach's scope of practice, advising when to refer clients to licensed mental health professionals. Trauma-informed coaching models are explored, offering structured approaches to address trauma while promoting growth and healing. The real-life case studies deepen understanding and provide practical insights into applying trauma-informed principles. The book underscores continuous learning, encouraging coaches to stay updated with the latest research and best practices. In conclusion, "The Trauma Informed Coach" by Joanna Harper is an invaluable resource that equips coaches and practitioners with the knowledge and skills needed to support clients dealing with past traumas and emotional injuries. With its compassionate approach, practical insights, and emphasis on professional boundaries, this book empowers coaches to create an environment where clients can truly flourish, thrive, and believe in their potential. Harper's expertise shines through every page, making this guide a must-read for anyone in the coaching field. September 22nd 2023

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Trauma-adapted yoga in forensic psychiatric care is feasible and yields positive effects, finds study

by University West

Previous studies in correctional facilities have shown positive effects of yoga on inmates. They experience increased impulse control and improved mental health. Are the same positive results seen in detained individuals with severe psychiatric disorders? Now, the first results from a large national and globally unique research study in forensic psychiatry from the University West are presented.

It is the first study of its kind to describe the effect and feasibility of trauma-adapted yoga in forensic psychiatry. The results of the study are published in Psychiatry Research .

"It is a breakthrough that we can now demonstrate the possibility of using yoga as a complementary care intervention in psychiatry and the positive effects it brings," says Nóra Kerekes, Professor in Medical Sciences (Psychiatry) at the University West, and research leader of the study.

"We wanted to explore whether previous positive results with the use of yoga in correctional facilities could be transferred to detained individuals suffering from severe psychiatric disorders. Therefore, we evaluated trauma-adapted yoga as a support within forensic psychiatry," says Kerekes.

Forensic psychiatry deals with the complex challenges that arise at the intersection of psychiatric illness, legal issues, and security concerns.

"There are few high-quality clinical studies on individuals who have committed crimes and who have a serious mental disorder. What exists are either studies on inmates separately or studies of individuals suffering from various psychiatric disorders. For both of these groups, yoga has shown positive effects," says Kerekes.

Self-choice was a central component in the study design, where 56 patients at various forensic psychiatric clinics chose to participate. Over 10 weeks, they either participated in specially developed yoga classes or chose to engage in other forms of physical activity. Throughout the study, changes in their mental health, emotional states, antisocial and aggressive behaviors, pain perception , substance cravings, and ability to control their behavior and emotional reactions were observed.

In the current study, the yoga group showed remarkable reductions in negative emotional states, anxiety, paranoid ideation, hostility, and overall psychological distress. These reductions were not observed in the group performing other forms of physical activities. Additionally, the yoga group exhibited a significant reduction in pain frequency, and showed strengthened self-control and accountability.

"We can conclude that trauma-adapted yoga implemented in a forensic psychiatric setting demonstrates feasibility and results in several positive changes in patients' mental health , emotional states, pain, and self-control ," says Kerekes.

"A structured program of trauma-adapted yoga for patients and training for health care personnel has been developed and has now been confirmed to be feasible and beneficial within forensic psychiatry ."

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A narrative review of the effects of dexamethasone on traumatic brain injury in clinical and animal studies: focusing on inflammation

• Published: 16 October 2023
• Volume 31 , pages 2955–2971, ( 2023 )

Cite this article

• Afsaneh Soltani 1 , 2 ,
• Uliana Y. Chugaeva 3 ,
• Montather F. Ramadan 4 ,
• Ebraheem Abdu Musad Saleh 5 ,
• Shaker Shanawa Al-Hasnawi 6 ,
• Rosario Mireya Romero-Parra 7 ,
• Ali Alsaalamy 8 ,
• Yasser Fakri Mustafa 9 ,
• Mohammad Yasin Zamanian   ORCID: orcid.org/0000-0003-0944-0320 10 , 11 , 12 &
• Maryam Golmohammadi 1  

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Traumatic brain injury (TBI) is a type of brain injury resulting from a sudden physical force to the head. TBI can range from mild, such as a concussion, to severe, which might result in long-term complications or even death. The initial impact or primary injury to the brain is followed by neuroinflammation, excitotoxicity, and oxidative stress, which are the hallmarks of the secondary injury phase, that can further damage the brain tissue. Dexamethasone (DXM) has neuroprotective effects. It reduces neuroinflammation, a critical factor in secondary injury-associated neuronal damage. DXM can also suppress the microglia activation and infiltrated macrophages, which are responsible for producing pro-inflammatory cytokines that contribute to neuroinflammation. Considering the outcomes of this research, some of the effects of DXM on TBI include: (1) DXM-loaded hydrogels reduce apoptosis, neuroinflammation, and lesion volume and improves neuronal cell survival and motor performance, (2) DXM treatment elevates the levels of Ndufs2, Gria3, MAOB, and Ndufv2 in the hippocampus following TBI, (3) DXM decreases the quantity of circulating endothelial progenitor cells, (4) DXM reduces the expression of IL1, (5) DXM suppresses the infiltration of RhoA + cells into primary lesions of TBI and (6) DXM treatment led to an increase in fractional anisotropy values and a decrease in apparent diffusion coefficient values, indicating improved white matter integrity. According to the study, the findings show that DXM treatment has neuroprotective effects in TBI. This indicates that DXM is a promising therapeutic approach to treating TBI.

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Angiogenesis and Functional Recovery After Traumatic Brain Injury

Therapeutic efficacy of neuro aid™ (mlc 601), a traditional chinese medicine, in experimental traumatic brain injury.

Ming-Che Tsai, Ching-Ping Chang, … Thomas Chang-Yao Tsao

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Data availability

Not applicable.

Abbreviations

• Traumatic brain injury
• Dexamethasone

Fractional anisotropy

Diffusion tensor imaging

Magnetic Resonance Imaging

Apparent diffusion coefficient

Diffusion-weighted imaging

Blood–brain barrier

Oxidative stress

Monoamine oxidase B

Glutamate receptor 3

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

Central nervous system

Fibroblast Growth Factor

Vascular Endothelial Growth Factor

Endothelial progenitor cells

Glucocorticoid receptor

Mineralocorticoid receptor

Progesterone receptor

Intercellular adhesion molecule-1

Conditioned place preference

Nucleus accumbens

Corticotropin-releasing hormone

Adrenocorticotropic hormone

Hypothalamic–pituitary–adrenal

Endothelial Monocyte-Activating Polypeptide II

Perivascular cells

Allograft Inflammatory Factor-1

Radial diffusivity

Mean diffusivity

Reactive oxygen species

Monoamine oxidases

Superoxide dismutases

Glutathione peroxidase

Alomair OI, Khan N, Smith MT, Brereton IM, Galloway GJ, Kurniawan ND (2021) Diffusion weighted magnetic resonance imaging revealed changes in the somatosensory and motor cortex of a mild relapsing-remitting experimental autoimmune encephalitis mouse model. Open Access J Biomed Sci 3:887–898

Google Scholar  

Ansari MA, Roberts KN, Scheff SW (2008) Oxidative stress and modification of synaptic proteins in hippocampus after traumatic brain injury. Free Radical Biol Med 45:443–452

Article   CAS   Google Scholar  

Assali M, Shawahna R, Shareef M, Alhimony I-A (2018) Dexamethasone-diclofenac loaded polylactide nanoparticles: Preparation, release and anti-inflammatory activity. Eur J Pharm Sci 122:179–184

Article   CAS   PubMed   Google Scholar  

Autieri MV, Carbone C, Mu A (2000) Expression of allograft inflammatory factor-1 is a marker of activated human vascular smooth muscle cells and arterial injury. Arterioscler Thromb Vasc Biol 20:1737–1744

Barden A, Phillips M, Hill LM, Fletcher EM, Mas E, Loh PS, French MA, Ho KM, Mori TA, Corcoran TB (2018) Antiemetic doses of dexamethasone and their effects on immune cell populations and plasma mediators of inflammation resolution in healthy volunteers. Prostaglandins Leukot Essent Fatty Acids 139:31–39

Bastin M, Carpenter T, Armitage P, Sinha S, Wardlaw J, Whittle I (2006) Effects of dexamethasone on cerebral perfusion and water diffusion in patients with high-grade glioma. Am J Neuroradiol 27:402–408

CAS   PubMed   PubMed Central   Google Scholar  

Bazarian JJ, Cernak I, Noble-Haeusslein L, Potolicchio S, Temkin N (2009) Long-term neurologic outcomes after traumatic brain injury. J Head Trauma Rehabil 24:439–451

Article   PubMed   Google Scholar  

Beppu T, Inoue T, Shibata Y, Kurose A, Arai H, Ogasawara K, Ogawa A, Nakamura S, Kabasawa H (2003) Measurement of fractional anisotropy using diffusion tensor MRI in supratentorial astrocytic tumors. J Neurooncol 63:109–116

Bereczki E, Branca RM, Francis PT, Pereira JB, Baek J-H, Hortobágyi T, Winblad B, Ballard C, Lehtiö J, Aarsland D (2018) Synaptic markers of cognitive decline in neurodegenerative diseases: a proteomic approach. Brain 141:582–595

Article   PubMed   PubMed Central   Google Scholar  

Brabeck C, Michetti F, Geloso MC, Corvino V, Goezalan F, Meyermann R, Schluesener HJ (2002) Expression of EMAP-II by activated monocytes/microglial cells in different regions of the rat hippocampus after trimethyltin-induced brain damage. Exp Neurol 177:341–346

Brinkmann V, Billich A, Baumruker T, Heining P, Schmouder R, Francis G, Aradhye S, Burtin P (2010) Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discov 9:883–897

Bryan CJ, Clemans TA, Hernandez AM, Rudd MD (2013) Loss of consciousness, depression, posttraumatic stress disorder, and suicide risk among deployed military personnel with mild traumatic brain injury. J Head Trauma Rehabil 28:13–20

Budde K, Schütz M, Glander P, Peters H, Waiser J, Liefeldt L, Neumayer HH, Böhler T (2006) FTY720 (fingolimod) in renal transplantation. Clin Transpl 20:17–24

Article   Google Scholar  

Capizzi A, Woo J, Verduzco-Gutierrez M (2020) Traumatic brain injury: an overview of epidemiology, pathophysiology, and medical management. Medical Clinics 104:213–238

PubMed   Google Scholar  

Carney N, Totten AM, O’Reilly C, Ullman JS, Hawryluk GW, Bell MJ, Bratton SL, Chesnut R, Harris OA, Kissoon N (2017) Guidelines for the management of severe traumatic brain injury. Neurosurgery 80:6–15

Castillo C, Saez-Orellana F, Godoy PA, Fuentealba J (2022) Microglial activation modulated by P2X4R in ischemia and repercussions in Alzheimer’s disease. Front Physiol 13:814999

Chalazonitis A (2004) Neurotrophin-3 in the development of the enteric nervous system. Prog Brain Res 146:243–263

Chaves T, Fazekas CL, Horváth K, Correia P, Szabó A, Török B, Bánrévi K, Zelena D (2021) Stress adaptation and the brainstem with focus on corticotropin-releasing hormone. Int J Mol Sci 22:9090

Article   CAS   PubMed   PubMed Central   Google Scholar  

Cheng G, Kong RH, Zhang LM, Zhang JN (2012) Mitochondria in traumatic brain injury and mitochondrial-targeted multipotential therapeutic strategies. Br J Pharmacol 167:699–719

Chiba K (2005) FTY720, a new class of immunomodulator, inhibits lymphocyte egress from secondary lymphoid tissues and thymus by agonistic activity at sphingosine 1-phosphate receptors. Pharmacol Ther 108:308–319

Chiba K, Matsuyuki H, Maeda Y, Sugahara K (2006) Role of sphingosine 1-phosphate receptor type 1 in lymphocyte egress from secondary lymphoid tissues and thymus. Cell Mol Immunol 3:11–19

CAS   PubMed   Google Scholar  

Cho E, Kutty JK, Datar K, Soo Lee J, Vyavahare NR, Webb K (2009) A novel synthetic route for the preparation of hydrolytically degradable synthetic hydrogels. J Biomed Mater Res a: off J Soc Biomater Jpn Soc Biomater Aust Soc Biomater Korean Soc Biomater 90:1073–1082

Cicerone KD, Mott T, Azulay J, Friel JC (2004) Community integration and satisfaction with functioning after intensive cognitive rehabilitation for traumatic brain injury. Arch Phys Med Rehabil 85:943–950

Cohen I, Liu X, Schutz C, White B, Jenkins E, Brown W, Holden J (2003) Association of autism severity with a monoamine oxidase A functional polymorphism. Clin Genet 64:190–197

Cornelius C, Crupi R, Calabrese V, Graziano A, Milone P, Pennisi G, Radak Z, Calabrese EJ, Cuzzocrea S (2013) Traumatic brain injury: oxidative stress and neuroprotection. Antioxid Redox Signal 19:836–853

Coutinho AE, Chapman KE (2011) The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol 335:2–13

Czekajlo MS, Milbrandt EB (2005) Corticosteroids increased short and long-term mortality in adults with traumatic head injury. Springer

David S, López-Vales R, Yong VW (2012) Harmful and beneficial effects of inflammation after spinal cord injury: potential therapeutic implications. Handb Clin Neurol 109:485–502

de Kloet ER, van Acker SA, Sibug RM, Oitzl MS, Meijer OC, Rahmouni K, de Jong W (2000) Brain mineralocorticoid receptors and centrally regulated functions. Kidney Int 57:1329–1336

De Leon-Oliva D, Garcia-Montero C, Fraile-Martinez O, Boaru DL, García-Puente L, Rios-Parra A, Garrido-Gil MJ, Casanova-Martín C, García-Honduvilla N, Bujan J (2023) AIF1: function and connection with inflammatory diseases. Biology 12:694

DeMaria AH (2021) Development of a hybrid hydrogel drug delivery system for treatment of ischemic injury. Clemson University.

Deshmane SL, Kremlev S, Amini S, Sawaya BE (2009) Monocyte chemoattractant protein-1 (MCP-1): an overview. J Interferon Cytokine Res 29:313–326

Dey R, Bishayi B (2019) Dexamethasone exhibits its anti-inflammatory effects in S. aureus induced microglial inflammation via modulating TLR-2 and glucocorticoid receptor expression. Int Immunopharmacol 75:105806

Dikmen S, Machamer J, Temkin N (2017) Mild traumatic brain injury: longitudinal study of cognition, functional status, and post-traumatic symptoms. J Neurotrauma 34:1524–1530

Dubreuil CI, Winton MJ, McKerracher L (2003) Rho activation patterns after spinal cord injury and the role of activated Rho in apoptosis in the central nervous system. J Cell Biol 162:233–243

Eichmann A, Simons M (2012) VEGF signaling inside vascular endothelial cells and beyond. Curr Opin Cell Biol 24:188–193

Estaquier J, Arnoult D (2007) Inhibiting Drp1-mediated mitochondrial fission selectively prevents the release of cytochrome c during apoptosis. Cell Death Differ 14:1086–1094

Faupel G, Reulen H, Müller D, Schürmann K (1976) Double-blind study on the effects of steroids on severe closed head injury. Dynamics of brain edema. Springer, pp 337–343

Chapter   Google Scholar  

Faupel G, Reulen H, Müller D, Schürmann K (1979) Dexamethasone in severe head injuries. Neurosurg Rev 2:105–111

Fesharaki-Zadeh A (2022) Oxidative stress in traumatic brain injury. Int J Mol Sci 23:13000

Finnie J (2013) Neuroinflammation: beneficial and detrimental effects after traumatic brain injury. Inflammopharmacology 21:309–320

Finsterwald C, Alberini CM (2014) Stress and glucocorticoid receptor-dependent mechanisms in long-term memory: from adaptive responses to psychopathologies. Neurobiol Learn Mem 112:17–29

Formicola D, Aloia A, Sampaolo S, Farina O, Diodato D, Griffiths LR, Gianfrancesco F, di Iorio G, Esposito T (2010) Common variants in the regulative regions of GRIA1 and GRIA3 receptor genes are associated with migraine susceptibility. BMC Med Genet 11:1–12

Garbarino VR, Orr ME, Rodriguez KA, Buffenstein R (2015) Mechanisms of oxidative stress resistance in the brain: lessons learned from hypoxia tolerant extremophilic vertebrates. Arch Biochem Biophys 576:8–16

Gasparini CF, Smith RA, Griffiths LR (2016) Genetic insights into migraine and glutamate: a protagonist driving the headache. J Neurol Sci 367:258–268

Glass WG, Sarisky RT, Vecchio AMD (2006) Not-so-sweet sixteen: the role of IL-16 in infectious and immune-mediated inflammatory diseases. J Interferon Cytokine Res 26:511–520

Gobiet W, Bock W, Liesegang J, Grote W (1976) Treatment of acute cerebral edema with high dose of dexamethasone. Intracranial pressure III, Springer

Book   Google Scholar  

Goncharova ND (2020) The HPA axis under stress and aging: individual vulnerability is associated with behavioral patterns and exposure time. BioEssays 42:2000007

Gorgoraptis N, Zaw-Linn J, Feeney C, Tenorio-Jimenez C, Niemi M, Malik A, Ham T, Goldstone AP, Sharp DJ (2019) Cognitive impairment and health-related quality of life following traumatic brain injury. NeuroRehabilitation 44:321–331

Grassi DC, Conceição DMD, Leite CDC, Andrade CS (2018) Current contribution of diffusion tensor imaging in the evaluation of diffuse axonal injury. Arq Neuropsiquiatr 76:189–199

Grossmann C, Almeida-Prieto B, Nolze A, de la Alvarez Rosa D (2022) Structural and molecular determinants of mineralocorticoid receptor signalling. Br J Pharmacol 179:3103–3311

Grote S, Böcker W, Mutschler W, Bouillon B, Lefering R (2011) Diagnostic value of the Glasgow coma scale for traumatic brain injury in 18,002 patients with severe multiple injuries. J Neurotrauma 28:527–534

Guo L-H, Mittelbronn M, Brabeck C, Mueller CA, Schluesener HJ (2004) Expression of interleukin-16 by microglial cells in inflammatory, autoimmune, and degenerative lesions of the rat brain. J Neuroimmunol 146:39–45

Gyoneva S, Ransohoff RM (2015) Inflammatory reaction after traumatic brain injury: therapeutic potential of targeting cell–cell communication by chemokines. Trends Pharmacol Sci 36:471–480

Habicht A, Clarkson MR, Yang J, Henderson J, Brinkmann V, Fernandes S, Jurewicz M, Yuan X, Sayegh MH (2006) Novel insights into the mechanism of action of FTY720 in a transgenic model of allograft rejection: implications for therapy of chronic rejection. J Immunol 176:36–42

Hakiminia B, Alikiaii B, Khorvash F, Mousavi S (2022) Oxidative stress and mitochondrial dysfunction following traumatic brain injury: from mechanistic view to targeted therapeutic opportunities. Fundam Clin Pharmacol 36:612–662

Halbauer JD, Ashford JW, Zeitzer JM, Adamson MM, Lew HL, Yesavage JA (2009) Neuropsychiatric diagnosis and management of chronic sequelae of war-related mild to moderate traumatic brain injury. J Rehabil Res Dev 46:757–796

Hillhouse T, Prus A (2021) Conditioned place preference test for assessing the rewarding effects of drugs of abuse. Brain Reward Syst 2:263–278

Hoge CW, Goldberg HM, Castro CA (2009) Care of war veterans with mild traumatic brain injury–flawed perspectives. N Engl J Med 360:1588

Honer C, Nam K, Fink C, Marshall P, Ksander G, Chatelain RE, Cornell W, Steele R, Schweitzer R, Schumacher C (2003) Glucocorticoid receptor antagonism by cyproterone acetate and RU486. Mol Pharmacol 63:1012–1020

Hossmann K-A, Fischer M, Bockhorst K, Hoehn-Berlage M (1994) NMR imaging of the apparent diffusion coefficient (ADC) for the evaluation of metabolic suppression and recovery after prolonged cerebral ischemia. J Cereb Blood Flow Metab 14:723–731

Hridi SU, Barbour M, Wilson C, Franssen AJ, Harte T, Bushell TJ, Jiang H-R (2021) Increased levels of IL-16 in the central nervous system during neuroinflammation are associated with infiltrating immune cells and resident glial cells. Biology 10:472

Hu T-H, Huang C-C, Wu C-L, Lin P-R, Liu S-Y, Lin J-W, Chuang J-H, Tai MH (2005) Increased endostatin/collagen XVIII expression correlates with elevated VEGF level and poor prognosis in hepatocellular carcinoma. Mod Pathol 18:663–672

Huisman T (2010) Diffusion-weighted and diffusion tensor imaging of the brain, made easy. Cancer Imaging 10:S163

Ismail H, Shakkour Z, Tabet M, Abdelhady S, Kobaisi A, Abedi R, Nasrallah L, Pintus G, Al-Dhaheri Y, Mondello S (2020) Traumatic brain injury: oxidative stress and novel anti-oxidants such as mitoquinone and edaravone. Antioxidants 9:943

Janssen RJ, Nijtmans LG, Heuvel LPVD, Smeitink JA (2006) Mitochondrial complex I: structure, function and pathology. J Inherit Metab Dis: off J Soc Study Inborn Errors Metab 29:499–515

Jeong DU, Bae S, Macks C, Whitaker J, Lynn M, Webb K, Lee JS (2021) Hydrogel-mediated local delivery of dexamethasone reduces neuroinflammation after traumatic brain injury. Biomed Mater 16:035002

Jobe AH, Milad MA, Peppard T, Jusko WJ (2020) Pharmacokinetics and pharmacodynamics of intramuscular and oral betamethasone and dexamethasone in reproductive age women in India. Clin Transl Sci 13:391–399

Juan CA, de la Pérezlastra JM, Plou FJ, Pérez-lebeña E (2021) The chemistry of reactive oxygen species (ROS) revisited: outlining their role in biological macromolecules (DNA, lipids and proteins) and induced pathologies. Int J Mol Sci 22:4642

Karve IP, Taylor JM, Crack PJ (2016) The contribution of astrocytes and microglia to traumatic brain injury. Br J Pharmacol 173:692–702

Kasckow J, Baker D, Geracioti T Jr (2001) Corticotropin-releasing hormone in depression and post-traumatic stress disorder. Peptides 22:845–851

Keating CE, Cullen DK (2021) Mechanosensation in traumatic brain injury. Neurobiol Dis 148:105210

Kim JG, Islam R, Cho JY, Jeong H, Cap KC, Park Y, Hossain AJ, Park JB (2018) Regulation of RhoA GTPase and various transcription factors in the RhoA pathway. J Cell Physiol 233:6381–6392

Knies UE, Behrensdorf HA, Mitchell CA, Deutsch U, Risau W, Drexler HC, Clauss M (1998) Regulation of endothelial monocyte-activating polypeptide II release by apoptosis. Proc Natl Acad Sci 95:12322–12327

Kobeissy FH, Shakkour Z, Hayek SE, Mohamed W, Gold MS, Wang KK (2022) Elevation of pro-inflammatory and anti-inflammatory cytokines in rat serum after acute methamphetamine treatment and traumatic brain injury. J Mol Neurosci 72:1–11

Kroemer G, Galluzzi L, Brenner C (2007) Mitochondrial membrane permeabilization in cell death. Physiol Rev 87:99–163

Krueger M, Bechmann I, Immig K, Reichenbach A, Härtig W, Michalski D (2015) Blood—brain barrier breakdown involves four distinct stages of vascular damage in various models of experimental focal cerebral ischemia. J Cereb Blood Flow Metab 35:292–303

Laberge S, Pinsonneault S, Varga E-M, Till SJ, Nouri-Aria K, Jacobson M, Cruikshank WW, Center DM, Hamid Q, Durham SR (2000) Increased expression of IL-16 immunoreactivity in bronchial mucosa after segmental allergen challenge in patients with asthma. J Allergy Clin Immunol 106:293–301

Larrabee GJ, Rohling ML (2013) Neuropsychological differential diagnosis of mild traumatic brain injury. Behav Sci Law 31:686–701

Larsen M, Willems WF, Pelzer M, Friedrich PF, Yaszemski MJ, Bishop AT (2010) Augmentation of surgical angiogenesis in vascularized bone allotransplants with host-derived a/v bundle implantation, fibroblast growth factor-2, and vascular endothelial growth factor administration. J Orthop Res 28:1015–1021

Lattin CR, Waldron-Francis K, Richardson JW, de Bruijn R, Bauer CM, Breuner CW, Romero LM (2012) Pharmacological characterization of intracellular glucocorticoid receptors in nine tissues from house sparrow ( Passer domesticus ). Gen Comp Endocrinol 179:214–220

Lee H-J, Kim C, Lee S-J (2010) Alpha-synuclein stimulation of astrocytes: potential role for neuroinflammation and neuroprotection. Oxid Med Cell Longev 3:283–287

Lozano D, Gonzales-Portillo GS, Acosta S, de la Pena I, Tajiri N, Kaneko Y, Borlongan CV (2015) Neuroinflammatory responses to traumatic brain injury: etiology, clinical consequences, and therapeutic opportunities. Neuropsychiatr Dis Treat 11:97–106

PubMed   PubMed Central   Google Scholar  

Ma X, Agas A, Siddiqui Z, Kim K, Iglesias-Montoro P, Kalluru J, Kumar V, Haorah J (2020) Angiogenic peptide hydrogels for treatment of traumatic brain injury. Bioactive Materials 5:124–132

Machado-Vieira R, Salvadore G, Ibrahim LA, Diaz-Granados N, Zarate CA Jr (2009) Targeting glutamatergic signaling for the development of novel therapeutics for mood disorders. Curr Pharm Des 15:1595–1611

Macks C, Jeong D, Bae S, Webb K, Lee JS (2022) Dexamethasone-loaded hydrogels improve motor and cognitive functions in a rat mild traumatic brain injury model. Int J Mol Sci 23:11153

Madzarac Z, Tudor L, Sagud M, Nedic Erjavec G, Mihaljevic Peles A, Pivac N (2021) The associations between COMT and MAO-B genetic variants with negative symptoms in patients with schizophrenia. Curr Issues Mol Biol 43:618–636

Majzoub JA (2006) Corticotropin-releasing hormone physiology. Eur J Endocrinol 155:S71–S76

Mancuso RA, Schetter CD, Rini CM, Roesch SC, Hobel CJ (2004) Maternal prenatal anxiety and corticotropin-releasing hormone associated with timing of delivery. Psychosom Med 66:762–769

Manteuffel G (2002) Central nervous regulation of the hypothalamic-pituitary-adrenal axis and its impact on fertility, immunity, metabolism and animal welfare–a review. Arch Anim Breed 45:575–595

Mathy N, Scheuer W, Lanzendörfer M, Honold K, Ambrosius D, Norley S, Kurth R (2000) Interleukin-16 stimulates the expression and production of pro-inflammatory cytokines by human monocytes. Immunology 100:63–69

Maxwell RE, Long DM, French LA (1971) The effects of glucosteroids on experimental cold-induced brain edema. Gross morphological alterations and vascular permeability changes. J Neurosurg 34:477–487

McCullers D, Sullivan P, Scheff S, Herman J (2002) Mifepristone protects CA1 hippocampal neurons following traumatic brain injury in rat. Neuroscience 109:219–230

Mcewen BS (2005) Glucocorticoids, depression, and mood disorders: structural remodeling in the brain. Metabolism 54:20–23

McKendrick G, Graziane NM (2020) Drug-induced conditioned place preference and its practical use in substance use disorder research. Front Behav Neurosci 14:582147

Meijer OC, Buurstede J, Schaaf MJ (2019) Corticosteroid receptors in the brain: transcriptional mechanisms for specificity and context-dependent effects. Cell Mol Neurobiol 39:539–549

Mena JH, Sanchez AI, Rubiano AM, Peitzman AB, Sperry JL, Gutierrez MI, Puyana JC (2011) Effect of the modified Glasgow coma scale score criteria for mild traumatic brain injury on mortality prediction: comparing classic and modified Glasgow coma scale score model scores of 13. J Trauma 71:1185

Merkel SF, Andrews AM, Lutton EM, Razmpour R, Cannella LA, Ramirez SH (2017) Dexamethasone attenuates the enhanced rewarding effects of cocaine following experimental traumatic brain injury. Cell Transplant 26:1178–1192

Meyer JH, Braga J (2022) Development and clinical application of positron emission tomography imaging agents for monoamine oxidase B. Front Neurosci 15:773404

Miller S, Yeh H (2017) Neurotransmitters and neurotransmission in the developing and adult nervous system. Conn’s Transl Neurosci 1:49–84

Mimaki M, Wang X, McKenzie M, Thorburn DR, Ryan MT (2012) Understanding mitochondrial complex I assembly in health and disease. Biochim Biophys Acta (BBA)-Bioenerg 1817:851–862

Moll A, Lara M, Pomar J, Orozco M, Frontera G, Llompart-Pou JA, Moratinos L, González V, Ibáñez J, Pérez-Bárcena J (2020) Effects of dexamethasone in traumatic brain injury patients with pericontusional vasogenic edema: a prospective-observational DTI-MRI study. Medicine 99:e22879

Monaghan P, Metcalfe NB, Torres R (2009) Oxidative stress as a mediator of life history trade-offs: mechanisms, measurements and interpretation. Ecol Lett 12:75–92

Montilla A, Mata GP, Matute C, Domercq M (2020) Contribution of P2X4 receptors to CNS function and pathophysiology. Int J Mol Sci 21:5562

Mueller C-A, Schluesener HJ, Conrad S, Meyermann R, Schwab JM (2003) Lesional expression of a proinflammatory and antiangiogenic cytokine EMAP II confined to endothelium and microglia/macrophages during secondary damage following experimental traumatic brain injury. J Neuroimmunol 135:1–9

Mulherkar S, Tolias KF (2020) RhoA-ROCK signaling as a therapeutic target in traumatic brain injury. Cells 9:245

Mulherkar S, Firozi K, Huang W, Uddin MD, Grill RJ, Costa-Mattioli M, Robertson C, Tolias KF (2017) RhoA-ROCK inhibition reverses synaptic remodeling and motor and cognitive deficits caused by traumatic brain injury. Sci Rep 7:10689

Nagao T, Qin C, Grosheva I, Maxfield FR, Pierini LM (2007) Elevated cholesterol levels in the plasma membranes of macrophages inhibit migration by disrupting RhoA regulation. Arterioscler Thromb Vasc Biol 27:1596–1602

Nagatsu T, Sawada M (2006) Molecular mechanism of the relation of monoamine oxidase B and its inhibitors to Parkinson’s disease: possible implications of glial cells. Oxid Stress Neuroprotection. https://doi.org/10.1007/978-3-211-33328-0_7

Nicolaides NC, Charmandari E, Chrousos GP, Kino T (2014) Circadian endocrine rhythms: the hypothalamic–pituitary–adrenal axis and its actions. Ann N Y Acad Sci 1318:71–80

Niogi SN, Mukherjee P (2010) Diffusion tensor imaging of mild traumatic brain injury. J Head Trauma Rehabil 25:241–255

Niu F, Zhang B, Feng J, Mao X, Xu X-J, Dong J-Q, Liu B-Y (2021) Protein profiling identified mitochondrial dysfunction and synaptic abnormalities after dexamethasone intervention in rats with traumatic brain injury. Neural Regen Res 16:2438

O’Donnell LJ, Westin C-F (2011) An introduction to diffusion tensor image analysis. Neurosurg Clin 22:185–196

O’Connor P, Comi G, Montalban X, Antel J, Radue E, de Vera A, Pohlmann H, Kappos L (2009) Oral fingolimod (FTY720) in multiple sclerosis: two-year results of a phase II extension study. Neurology 72:73–79

O’Reilly MS, Boehm T, Shing Y, Fukai N, Vasios G, Lane WS, Flynn E, Birkhead JR, Olsen BR, Folkman J (1997) Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 88:277–285

Özdemir Z, Alagöz MA, Bahçecioğlu ÖF, Gök S (2021) Monoamine oxidase-B (MAO-B) inhibitors in the treatment of Alzheimer’s and Parkinson’s disease. Curr Med Chem 28:6045–6065

Paradies G, Paradies V, Ruggiero FM, Petrosillo G (2014) Oxidative stress, cardiolipin and mitochondrial dysfunction in nonalcoholic fatty liver disease. World J Gastroenterol: WJG 20:14205

Patergnani S, Suski JM, Agnoletto C, Bononi A, Bonora M, de Marchi E, Giorgi C, Marchi S, Missiroli S, Poletti F (2011) Calcium signaling around mitochondria associated membranes (MAMs). Cell Commun Signal 9:1–10

Paul SN, Wingenfeld K, Otte C, Meijer OC (2022) Brain mineralocorticoid receptor in health and disease: from molecular signalling to cognitive and emotional function. Br J Pharmacol 179:3205–3219

Pérez-Bárcena J, Castaño-León AM, Gómez-Abascal AL, Barea-Mendoza JA, Maín BN, Pons JP, Párraga LDMP, Domínguez JI, Chico-Fernández M, Llompart-Pou JA (2021) Dexamethasone for the treatment of traumatic brain injured patients with brain contusions and pericontusional edema: Study protocol for a prospective, randomized and double blind trial. Medicine 100:e24206

Pezzella F, Kerbel RS (2022) On coalescent angiogenesis and the remarkable flexibility of blood vessels. Angiogenesis 25:1–3

Pinschewer DD, Ochsenbein AF, Odermatt B, Brinkmann V, Hengartner H, Zinkernagel RM (2000) FTY720 immunosuppression impairs effector T cell peripheral homing without affecting induction, expansion, and memory. J Immunol 164:5761–5770

Ponsford J, Willmott C, Rothwell A, Cameron P, Kelly A-M, Nelms R, Curran C, Ng K (2000) Factors influencing outcome following mild traumatic brain injury in adults. J Int Neuropsychol Soc 6:568–579

Priault M, Salin B, Schaeffer J, Vallette FD, di Rago J, Martinou J (2005) Impairing the bioenergetic status and the biogenesis of mitochondria triggers mitophagy in yeast. Cell Death Differ 12:1613–1621

Prince C, Bruhns ME (2017) Evaluation and treatment of mild traumatic brain injury: the role of neuropsychology. Brain Sci 7:105

Qiu Z, Wang Y, Zhang Z, Qin R, Peng Y, Tang W, Xi Y, Tian G, Zhang Y (2022) Roles of intercellular cell adhesion molecule-1 (ICAM-1) in colorectal cancer: expression, functions, prognosis, tumorigenesis, polymorphisms and therapeutic implications. Front Oncol 12:1052672

Rao PS, Kalva S, Yerramilli A, Mamidi S (2011) Free radicals and tissue damage: role of antioxidants. Free Radic Antioxid 1:2–7

Ren K, Yuan H, Zhang Y, Wei X, Wang D (2015) Macromolecular glucocorticoid prodrug improves the treatment of dextran sulfate sodium-induced mice ulcerative colitis. Clin Immunol 160:71–81

Russo MV, McGavern DB (2016) Inflammatory neuroprotection following traumatic brain injury. Science 353:783–785

Sahel DK, Kaira M, Raj K, Sharma S, Singh S (2019) Mitochondrial dysfunctioning and neuroinflammation: recent highlights on the possible mechanisms involved in traumatic brain injury. Neurosci Lett 710:134347

Sanfilippo C, Castrogiovanni P, Imbesi R, di Rosa M (2020) CHI3L2 expression levels are correlated with AIF1, PECAM1, and CALB1 in the brains of Alzheimer’s disease patients. J Mol Neurosci 70:1598–1610

Sarkar C, Zhao Z, Aungst S, Sabirzhanov B, Faden AI, Lipinski MM (2014) Impaired autophagy flux is associated with neuronal cell death after traumatic brain injury. Autophagy 10:2208–2222

Savelli S, di Maurizio M, Perrone A, Tesei J, Francioso A, Angeletti M, la Barbera L, Ballesio L, de Felice C, Porfiri LM (2007) MRI with diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) assessment in the evaluation of normal and abnormal fetal kidneys: preliminary experience. Prenat Diagn 27:1104–1111

Scherma M, Fattore L, Fratta W, Fadda P (2021) Conditioned place preference (CPP) in rats: from conditioning to reinstatement test. Opioid Recept: Methods Protoc 2021(2201):221–229

Schiff M, de Baulny HO, Lombès A (2011) Neonatal cardiomyopathies and metabolic crises due to oxidative phosphorylation defects. Semin Fetal Neonatal Med 16:216–221

Schluesener HJ, Seid K, Zhao Y, Meyermann R (1997) Localization of endothelial-monocyte-activating polypeptide II (EMAP II), a novel proinflammatory cytokine, to lesions of experimental autoimmune encephalomyelitis, neuritis and uveitis: expression by monocytes and activated microglial cells. Glia 20:365–372

Schwab J, Nguyen T, Meyermann R, Schluesener H (2001) Human focal cerebral infarctions induce differential lesional interleukin-16 (IL-16) expression confined to infiltrating granulocytes, CD8+ T-lymphocytes and activated microglia/macrophages. J Neuroimmunol 114:232–241

Sener RN (2001) Diffusion MRI: apparent diffusion coefficient (ADC) values in the normal brain and a classification of brain disorders based on ADC values. Comput Med Imaging Graph 25:299–326

Shao F, Wang X, Wu H, Wu Q, Zhang J (2022) Microglia and neuroinflammation: crucial pathological mechanisms in traumatic brain injury-induced neurodegeneration. Front Aging Neurosci 14:825086

Shinozaki C, Kohno K, Shiroishi M, Takahashi D, Yoshikawa Y, Abe Y, Hamase K, Nakakido M, Tsumoto K, Inoue K (2022) Improvement of the affinity of an anti-rat P2X4 receptor antibody by introducing electrostatic interactions. Sci Rep 12:131

Sikora M, Kopeć B, Piotrowska K, Pawlik A (2020) Role of allograft inflammatory factor-1 in pathogenesis of diseases. Immunol Lett 218:1–4

Singh A, Kukreti R, Saso L, Kukreti S (2019) Oxidative stress: a key modulator in neurodegenerative diseases. Molecules 24:1583

Singh V, Kaur R, Kumari P, Pasricha C, Singh R (2023) ICAM-1 and VCAM-1: gatekeepers in various inflammatory and cardiovascular disorders. Clin Chim Acta 548:117487

Sinha S, Bastin M, Wardlaw J, Armitage P, Whittle I (2004) Effects of dexamethasone on peritumoural oedematous brain: a DT-MRI study. J Neurol Neurosurg Psychiatry 75:1632–1635

Sinkus R, van Beers BE, Vilgrain V, Desouza N, Waterton JC (2012) Apparent diffusion coefficient from magnetic resonance imaging as a biomarker in oncology drug development. Eur J Cancer 48:425–431

Soares JM, Marques P, Alves V, Sousa N (2013) A hitchhiker’s guide to diffusion tensor imaging. Front Neurosci 7:31

Song K, Li Y, Zhang H, An N, Wei Y, Wang L, Tian C, Yuan M, Sun Y, Xing Y (2020) Oxidative stress-mediated blood-brain barrier (BBB) disruption in neurological diseases. Oxid Med Cell Longev 2020:1–27

Sun Y, Wang S, Liu B, Hu W, Zhu Y (2023) Host-microbiome interactions: tryptophan metabolism and aromatic hydrocarbon receptors after traumatic brain injury. Int J Mol Sci 24:10820

Sutherland-Smith J, King R, Faissler D, Ruthazer R, Sato A (2011) Magnetic resonance imaging apparent diffusion coefficients for histologically confirmed intracranial lesions in dogs. Vet Radiol Ultrasound 52:142–148

Tanriverdi F, Ulutabanca H, Unluhizarci K, Selcuklu A, Casanueva FF, Kelestimur F (2008) Three years prospective investigation of anterior pituitary function after traumatic brain injury: a pilot study. Clin Endocrinol 68:573–579

Taylor AN, Rahman SU, Tio DL, Gardner SM, Kim CJ, Sutton RL (2010) Injury severity differentially alters sensitivity to dexamethasone after traumatic brain injury. J Neurotrauma 27:1081–1089

Thal SC, Schaible E-V, Neuhaus W, Scheffer D, Brandstetter M, Engelhard K, Wunder C, Förster CY (2013) Inhibition of proteasomal glucocorticoid receptor degradation restores dexamethasone-mediated stabilization of the blood–brain barrier after traumatic brain injury. Crit Care Med 41:1305–1315

Tsigos C, Chrousos GP (2002) Hypothalamic–pituitary–adrenal axis, neuroendocrine factors and stress. J Psychosom Res 53:865–871

Twomey EC, Yelshanskaya MV, Grassucci RA, Frank J, Sobolevsky AI (2017) Channel opening and gating mechanism in AMPA-subtype glutamate receptors. Nature 549:60–65

Tyczewska M, Szyszka M, Jopek K, Ruciński M (2022) Effects of galp and alarin peptides on HPA axis gene expression and adrenal function: in vivo experiments. Adv Clin Exp Med 31:643–654

Verma M, Lizama BN, Chu CT (2022) Excitotoxicity, calcium and mitochondria: a triad in synaptic neurodegeneration. Transl Neurodegener 11:3

Walia A, Yang JF, Huang Y-H, Rosenblatt MI, Chang J-H, Azar DT (2015) Endostatin’s emerging roles in angiogenesis, lymphangiogenesis, disease, and clinical applications. Biochem Biophys Acta 1850:2422–2438

Wang M, Luo L (2020) An effective NADPH oxidase 2 inhibitor provides neuroprotection and improves functional outcomes in animal model of traumatic brain injury. Neurochem Res 45:1097–1106

Wang H, Zhou X-M, Wu L-Y, Liu G-J, Xu W-D, Zhang X-S, Gao Y-Y, Tao T, Zhou Y, Lu Y (2020) Aucubin alleviates oxidative stress and inflammation via Nrf2-mediated signaling activity in experimental traumatic brain injury. J Neuroinflammation 17:1–18

Watson S, Mackin P (2006) HPA axis function in mood disorders. Psychiatry 5:166–170

Wei X, Zhao G, Jia Z, Zhao Z, Chen N, Sun Y, Kelso M, Rathore G, Wang D (2022) Macromolecular dexamethasone prodrug ameliorates neuroinflammation and prevents bone loss associated with traumatic brain injury. Mol Pharm 19:4000–4009

Weiss MH, Nulsen FE (1970) The effect of glucocorticoids on CSF flow in dogs. J Neurosurg 32:452–458

Wu Y, Krüttgen A, Möller J, Shine D, Chan J, Shooter E, Cosgaya J (2004) Nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 are sorted to dense-core vesicles and released via the regulated pathway in primary rat cortical neurons. J Neurosci Res 75:825–834

Wu A-G, Yong Y-Y, Pan Y-R, Zhang L, Wu J-M, Zhang Y, Tang Y, Wei J, Yu L, Law BY-K (2022) Targeting Nrf2-mediated oxidative stress response in traumatic brain injury: therapeutic perspectives of phytochemicals. Oxid Med Cell Longev. https://doi.org/10.1155/2022/1015791

Wyser-Pratte RC (2000) Protection of RU-486 as contraception, emergency contraception and as an abortifacient under the law of contraception. Oregon Law Rev 79:1121–1156

Yang S-E, Hsieh M-T, Tsai T-H, Hsu S-L (2002) Down-modulation of Bcl-XL, release of cytochrome c and sequential activation of caspases during honokiol-induced apoptosis in human squamous lung cancer CH27 cells. Biochem Pharmacol 63:1641–1651

Yang J-T, Lee T-H, Weng H-H, Chang C-N, Chen W-C, Cheng W-C, Wu JH (2005a) Dexamethasone enhances NT-3 expression in rat hippocampus after traumatic brain injury. Exp Neurol 192:437–443

Yang ZF, Ho DW, Lau CK, Lam CT, Lum CT, Poon RT, Fan ST (2005b) Allograft inflammatory factor-1 (AIF-1) is crucial for the survival and pro-inflammatory activity of macrophages. Int Immunol 17:1391–1397

Zamanian MY, Taheri N, Opulencia MJC, Bokov DO, Abdullaev SY, Gholamrezapour M, Heidari M, Bazmandegan G (2022) Neuroprotective and anti-inflammatory effects of pioglitazone on traumatic brain injury. Mediators Inflamm. https://doi.org/10.1155/2022/9860855

Zatterstrom UK, Felbor U, Fukai N, Olsen BR (2000) Collagen XVIII/endostatin structure and functional role in angiogenesis. Cell Struct Funct 25:97–101

Zhang K, Luo J (2019) Role of MCP-1 and CCR2 in alcohol neurotoxicity. Pharmacol Res 139:360–366

Zhang Z-Y, Zhang Z, Fauser U, Artelt M, Burnet M, Schluesener H (2007a) Dexamethasone transiently attenuates up-regulation of endostatin/collagen XVIII following traumatic brain injury. Neuroscience 147:720–726

Zhang Z, Zhang Z, Artelt M, Burnet M, Schluesener HJ (2007b) Dexamethasone attenuates early expression of three molecules associated with microglia/macrophages activation following rat traumatic brain injury. Acta Neuropathol 113:675–682

Zhang Z, Zhang Z, Fauser U, Artelt M, Burnet M, Schluesener HJ (2007c) FTY720 attenuates accumulation of EMAP-II+ and MHC-II+ monocytes in early lesions of rat traumatic brain injury. J Cell Mol Med 11:307–314

Zhang Z, Fauser U, Schluesener H (2008a) Early attenuation of lesional interleukin-16 up-regulation by dexamethasone and FTY720 in experimental traumatic brain injury. Neuropathol Appl Neurobiol 34:330–339

Zhang Z, Fauser U, Schluesener HJ (2008b) Dexamethasone suppresses infiltration of RhoA+ cells into early lesions of rat traumatic brain injury. Acta Neuropathol 115:335–343

Zhang B, Zhu X, Wang L, Hao S, Xu X, Niu F, He W, Liu B (2019) Dexamethasone impairs neurofunctional recovery in rats following traumatic brain injury by reducing circulating endothelial progenitor cells and angiogenesis. Brain Res 1725:146469

Zhang B, Xu X, Niu F, Mao X, Dong J, Yang M, Gao F, Liu B (2020) Corticosterone replacement alleviates hippocampal neuronal apoptosis and spatial memory impairment induced by dexamethasone via promoting brain corticosteroid receptor rebalance after traumatic brain injury. J Neurotrauma 37:262–272

Zhao Z, Jiang H, Xu X, Jia Z, Ren R, Foster KW, Wei X, Chen N, Goldring SR, Crow MK (2022) Polymeric dexamethasone prodrugs attenuate lupus nephritis in MRL/lpr mice with reduced glucocorticoid toxicity. Nanomedicine: Nanotechnol Biol Med. 44:1025

Zhou P, Wang H, Shi G, Wang X, Shen Z, Xu D (2009) Immunomodulatory drug FTY720 induces regulatory CD4+ CD25+ T cells in vitro. Clin Exp Immunol 157:40–47

Zhu W, Cui G, Li T, Chen H, Zhu J, Ding Y, Zhao L (2020) Docosahexaenoic acid protects traumatic brain injury by regulating NOX 2 generation via Nrf2 signaling pathway. Neurochem Res 45:1839–1850

Ziebell JM, Morganti-Kossmann MC (2010) Involvement of pro-and anti-inflammatory cytokines and chemokines in the pathophysiology of traumatic brain injury. Neurotherapeutics 7:22–30

Zorov DB, Juhaszova M, Sollott SJ (2014) Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev 94:909–950

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Afsaneh Soltani & Maryam Golmohammadi

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Afsaneh Soltani

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Uliana Y. Chugaeva

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Montather F. Ramadan

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Mohammad Yasin Zamanian

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UYC and MFR: investigation, EAMS and SSA: resources, RMRP, YFM and AA: data curation, AS and MYZ: writing—original draft preparation, MG, AS and MYZ.; writing—review and editing, MYZ: visualization, MYZ and AS: supervision, MYZ and MG; project administration. All authors have read and agreed to the published version of the manuscript.

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Soltani, A., Chugaeva, U.Y., Ramadan, M.F. et al. A narrative review of the effects of dexamethasone on traumatic brain injury in clinical and animal studies: focusing on inflammation. Inflammopharmacol 31 , 2955–2971 (2023). https://doi.org/10.1007/s10787-023-01361-3

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Received : 07 August 2023

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Issue Date : December 2023

DOI : https://doi.org/10.1007/s10787-023-01361-3

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Case Report

Traumatic brain injury and the evidence for its management.

A 29-year-old man presented to a major trauma centre with traumatic brain injury. Following cranial decompression, the patient was admitted to the intensive care unit for medical management and monitoring. This case report reviews the evidence for the management of traumatic brain injury.

Traumatic brain injury (TBI) is a key cause of death and disability in young adults and is becoming more prevalent. 1 While advances in prehospital care have reduced all-cause mortality following major trauma, a reduction in mortality following TBI has not occurred since 1994. 1 Intracranial pressure (ICP) and cerebral perfusion pressure (CPP) monitoring represents ‘gold-standard’ care, but its use in guiding patient management is controversial. 2 The study presents a case of TBI and reviews the literature to understand the rationale for ICP monitoring and its role in patient management.

Case presentation

A 29-year-old man presented to a major trauma centre by land ambulance having sustained a witnessed fall from the third floor. On arrival at the emergency department (ED), he was combative and vomiting. Owing to his agitated behaviour, the ambulance crew had been unable to immobilise his cervical spine (C-spine) and place the patient onto a hardboard.

His airway was initially managed with simple airway manoeuvres. He was placed in the lateral position and secretions suctioned. His Glasgow Coma Scale (GCS) was 12 (eyes 3; verbal 3; motor 6). His pupils were reactive bilaterally (2+/2+). The decision was made to perform a rapid sequence induction in order to protect his airway and safely perform investigations. The patient was preoxygenated and induced with 50 mg propofol, 150 µg fentanyl and 100 mg rocuronium. Cricoid pressure was applied and a size 8 endotracheal tube placed to 21 cm at the lips and secured. He was transferred directly from the ED resuscitation room to the CT scanner.

Investigations

This plane CT scan of the head reveals an acute traumatic subdural haematoma within the right frontoparietal convexity. Subdural collections are typically crescent shaped and are limited by dural reflections such as the falx cerebri. The brain is oedematous with loss of sulci and gyri.

This plane CT reveals a fracture within the right temporal bone with overlying cutaneous haematoma. Subarachnoid blood is demonstrated by the hyperattenuating material within the lateral ventricles.

This CT intracranial angiogram demonstrates the intracranial vascular anatomy. The middle cerebral arteries course laterally and are united by the anterior communicating artery. Posterior cerebral arteries opacify normally. The Circle of Willis is completed by the posterior communicating arteries.

• A CT of the chest, abdomen and pelvis was performed to exclude the presence of either solid or hollow organ injury. This excluded a haemothorax/pneumothorax and the heart and mediastinal vessels opacified normally. No intra-abdominal injury was identified but multiple thoracic spine fractures with mild-to-moderate wedge compression were evident in T3, T5 and T9.

Differential

Traumatic brain injury.

This patient has presented to the ED with a reduced GCS, vomiting and combative behaviour. These clinical features are highly suggestive of an intracranial injury. The principle diagnoses are an extradural haematoma, subdural haematoma or a subarachnoid haemorrhage. Extradural haematomas are commonly associated with skull fractures and are caused by the tearing of a meningeal artery or dural venous sinus. Blood collects between the dura and skull causing compression of brain tissue and transtentorial herniation. Subdural haematomas are caused by bleeding from bridging veins that cross the subdural space. Subdural collections occur commonly following an assault or fall. Subarachnoid blood collects within the subarachnoid space between the arachnoid and pia mater. Hypoxic brain injury resulting in permanent disability and hydrocephalus caused by occlusion of cerebrospinal fluid (CSF) circulation are common sequelae.

Blunt visceral injury

A fall from a height can result in deceleration injury to the mediastinal vasculature, particularly at the junction of the mobile aortic arch and fixed descending aorta. This can lead to dissection or transection of the vessel. Haemothoraces/pneumothoraces are potentially fatal conditions which require rapid evaluation and treatment. Solid intra-abdominal organs are particularly vulnerable following falls. The liver and spleen are susceptible to rupture leading to blood loss.

Pelvic and spinal fractures

The rigid bony pelvis is vulnerable to anteroposterior, lateral compression and vertical shear fracture. Owing to the close proximity of the iliac vessels and presacral venous plexus, haemorrhage is a major cause of death from displacement of the pelvic ring. Confirmation of pelvic stability is mandatory in those who have fallen from a height. Long bone fractures and spinal injury should also be excluded.

Surgery—right decompressive craniectomy

The patient underwent an emergency decompressive craniectomy, minimal right parietal lobectomy and ICP bolt insertion. The surgical site was prepared and the trauma flap raised. On inspection, the brain appeared swollen and tight. The dura was incised and the clot evacuated. Following evacuation of the clot, the brain continued to swell mandating extension of the craniectomy anteriorly by 2–3 cm. Extension of the craniectomy permitted brain swelling and the reduction of ICP via the Monro-Kellie hypothesis. The wound was closed and an ICP bolt placed over the left frontal lobe. The pressure on insertion was 17 mm Hg.

Neuroprotective measures

The patient was transferred directly to the intensive care unit (ICU) for medical management and monitoring. His ICP and CPP were controlled by ventilatory and pharmacological strategies. Over 5 days, his sedation was weaned and he was extubated in order to assess his neurological function.

Outcome and follow-up

On waking from sedation, the patient had a dense left-sided hemiplegia and aphasia. His GCS off all sedation was 11 (eyes 4; verbal 1; motor 6). He remained in the ICU for several weeks and required a tracheostomy to facilitate suctioning of secretions and prevent aspiration pneumonia. Following removal of the ICP bolt, he had a further CT scan of the head in order to plan a cranioplasty. After a prolonged stay, the patient was stepped down to the neuromonitored ward for ongoing physiotherapy and rehabilitation.

TBI can be subdivided into primary and secondary injury. Primary injury results from an external force disrupting intracranial structures. The intensity and duration of these forces determine the extent of the damage, which may include shearing of white matter tracts, contusions, haematomas and swelling. Secondary brain injury evolves following the primary insult. Cerebral metabolism is impaired causing anaerobic glycolysis and the accumulation of lactic acid. 3 Membrane permeability and cerebral oedema results. Deregulation of cerebral blood flow (CBF) and neurotransmitter release causing excitotoxicity, free-radical generation and mitochondrial dysfunction.

The principle of ICP monitoring is to maintain adequate cerebral perfusion and oxygenation to meet metabolic demands. 4 Raised ICP reduces CPP and CBF, which exacerbates secondary injury. 4 Several studies have shown that a high ICP is strongly associated with poor outcome and may lead to brainstem pressure, herniation, respiratory depression and death. 4 Level I and level II evidence for ICP monitoring influencing outcome is lacking. 2 In one randomised trial of ICP versus clinical examination plus imaging, there was no significant improvement in survival between the study groups. 2 Similar findings have been confirmed by other studies that have concluded that ICP-targeted/CPP-targeted intensive care prolongs mechanical ventilation and increases therapy intensity without evidence of improved outcome. 5 However, management guidelines endorsed by the American Association of Neurological Surgeons (AANS) advocate the use of ICP monitoring for those at risk of intracranial hypertension. 4 Contradictory studies purport reduced mortality and improved outcomes in those with ICP monitoring. 4 The IMPACT meta-analysis reviewed reversible insults present on admission and their potential to influence outcome by exacerbating secondary injury. Hypoxia (arterial pO 2 <60 mm Hg) (OR=2.1; 95% CI 1.7 to 2.6), hypotension (systolic blood pressure (SBP) <90 mm Hg) (OR=2.7; 95% CI 2.1 to 3.4) and hypothermia (temperature <35°C) (OR=2.2; 95% CI 1.6 to 3.2) were strongly associated with poor outcomes, with hypoxia and hypotension having synergistic effects. 6 The reversibility of these physiological insults reinforces the need for close monitoring in a critical care environment, where the early instigation of corrective therapy may restore normal physiology and improve outcome. 6

Intracranial pressure

Several studies have shown that patients with an ICP<20 mm Hg have a reduced risk of neurological deterioration, (relative risk (RR) 0.341 (95% CI 0.252 to 0.461; p<0.00001)), compared with higher ICPs (ICP≥25 mm Hg; RR=3.042 (95% CI 2.288 to 4.045; p<0.00001)). 7 Mortality also increases dramatically from 17% to 47% when an average ICP>20 mm Hg (p<0.0001). 8 However, ICP monitoring is complicated by infection in up to 22% of cases, the risk dramatically increasing >5 days following insertion (RR=4.0; 95% CI 1.3 to 11.9). 9 Regular CSF analysis to diagnose ventriculitis is recommended, which increases cost and consumes resources. 9

Cerebral perfusion pressure

TBI has been managed by increasing mean arterial pressure and CPP with pharmacological agents such as dopamine and norepinephrine. 10 Some have suggested that targeted therapy aimed at improving CPP is of greater significance than lowering ICP. 10 Studies have revealed that mortality rates for CPP<55 mm Hg are much greater than those with a CPP>55 mm Hg (81% vs 23% respectively; p<0.0001). 10 Meanwhile, a CPP>95 mm Hg has a detrimental impact on a positive neurological outcome (CPP<95 mm Hg=50% vs CPP>95 mm Hg=28%; p<0.033). 10 Others have failed to illustrate a statistically significant influence from CPP measurement alone.

Cerebral blood flow

Cerebral vasoreactivity ensures constant CBF. One treatment strategy for raised ICP focuses on hyperventilation causing cerebral vasoconstriction and reduced CBF. 4 One randomised control trial assigned patients to receive normal ventilation (PaCO 2 =35±2 mm Hg) or hyperventilation (PaCO 2 =25±2 mm Hg) and found favourable neurological outcome to be significantly lower in the hyperventilated group (p<0.05). 11 AANS therefore recommends avoiding hyperventilation and maintenance of normocarbia, other than as a temporising measure to reduce elevated ICP. 4

Does ICP monitoring affect management?

Increasing ICP measurements are often the first indicator of an evolving mass lesion, 80% of which require surgery. 4 Decompressive craniectomy removes part of the skull permitting cerebral swelling and reducing ICP. However, the procedure has not gained complete acceptance due to the poor functional outcome of surviving patients. 12 A multicentre randomised controlled trial of decompressive craniectomy versus standard therapy (DECRA trial) found that those receiving a craniectomy spent less time with raised ICPs (p<0.001), received fewer interventions (p<0.02) and spent fewer days in critical care (p<0.001). 12 However, they had worse extended Glasgow Outcome Scale scores (OR=1.84; 95% CI 1.05 to 3.24; p=0.03) and a greater risk of an unfavourable outcome (OR=2.21; 95% CI 1.14 to 4.26; p=0.02). 12 Others have contradicted this, suggesting good neurological outcomes in those surviving >30 days following craniectomy. 13 Those with admission GCS>6 were particularly good candidates for the procedure. 13 Randomised Evaluation of Surgery with Craniectomy for Uncontrollable Elevation of intra-cranial pressure (RESCUE-icp) study aims to determine the effectiveness of decompressive craniectomy and better define the indications for surgery. Hypertonic solutes such as 7.5% saline and 20% mannitol have been used to treat refractory intracranial hypertension, with some studies suggesting the superiority of saline over mannitol. 4 14 Others have treated patients with hypotension with 7.5% saline or Ringer's lactate solution and found little difference in favourable neurological outcome (risk ratio 0.99; 95% CI 0.76 to 1.30; p=0.96). 15 AANS advocates the use of hyperosmolar therapy for the control of raised ICP, though hypotension (SBP<90 mm Hg) should be avoided. 4

Learning points

• Primary injury refers to the initial insult caused by traumatic force, while secondary injury refers to delayed injury caused by tissue hypoxia and raised intracranial pressure (ICP).
• The Monro-Kellie hypothesis is key to understanding ICP and cerebral perfusion pressure (CPP) following traumatic brain injury (TBI). The rigid skull results in a fixed intracranial volume. Normal ICP is comprised of three components: brain tissue, cerebrospinal fluid and blood. If one component is elevated, ICP will increase unless the volume of the other two components decreases proportionately. Brain shift and herniation occur following a critical increase in ICP. This may manifest clinically as a drop in Glasgow Coma Scale.
• CPP=mean arterial pressure−ICP. The effects of raised ICP are exerted on the cerebral vasculature causing a progressive reduction in CPP.
• A review of the literature reveals a lack of evidence and contradictory evidence for many strategies used in the monitoring and treatment of TBI.

Competing interests: None declared.

Patient consent: Obtained.

Provenance and peer review: Not commissioned; externally peer reviewed.

Evidence Review of the Adverse Effects of COVID-19 Vaccination and Intramuscular Vaccine Administration

Vaccines are a public health success story, as they have prevented or lessened the effects of many infectious diseases. To address concerns around potential vaccine injuries, the Health Resources and Services Administration (HRSA) administers the Vaccine Injury Compensation Program (VICP) and the Countermeasures Injury Compensation Program (CICP), which provide compensation to those who assert that they were injured by routine vaccines or medical countermeasures, respectively. The National Academies of Sciences, Engineering, and Medicine have contributed to the scientific basis for VICP compensation decisions for decades.

HRSA asked the National Academies to convene an expert committee to review the epidemiological, clinical, and biological evidence about the relationship between COVID-19 vaccines and specific adverse events, as well as intramuscular administration of vaccines and shoulder injuries. This report outlines the committee findings and conclusions.

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• Digital Resource: Evidence Review of the Adverse Effects of COVID-19 Vaccination
• Digital Resource: Evidence Review of Shoulder Injuries from Intramuscular Administration of Vaccines
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