case study family history

The Family History Guide Blog

… See the latest news about your free learning and training site for family history!

The Value of Case Studies in Family History

“Could I have an example, please?” This is one of the most common questions we all have, about almost any subject, whether or not we ask it out loud. Good examples help us connect the dots in our learning. They help us see relationships between pieces of information, how cause and effect works, and how we can apply principles in a variety of ways.

On the other hand, an example that’s unfocused or unclear might be confusing and worse than no example at all.

It’s much the same in family history. We can find some great tools or pieces of information, but how do we apply them in our own research? That’s where a good case study can be really valuable. It not only walks us through solving a research problem, but it also does the following:

• Highlights the principles that were used
• Explains why they were effective
• Offers suggestions on how you might use them in your research

As you might expect, not all case studies are created equal. Sometimes you have to dig a bit to identify the principles and how you can use them. Be prepared to use “intelligent filters”—skip past any parts that are repetitious or wandering, and read between the lines to find nuggets of information you might need. In some ways, it’s like mining a historical record for insights. The tips and trick you learn will prove valuable as you search for clues in your own ancestors’ stories.

In this newspaper case study, the author helps us find research clues by using the following elements:

• Background : This sets the stage for the person we are following.
• Comparisons : The primary account of the story is compared with accounts from other newspapers. This shows the value of working with multiple sources in research.
• Next Steps : The author suggests additional approaches and record searches. This is good for a brief case study, while more extensive ones will provide details of what was found in the extra research.
• Takeaway : This is the main point learned from the case study. You can add your own takeaways, from your analysis of what you have read.

Case Studies in The Family History Guide

There are plenty of links to research case studies in The Family History Guide, from basic record finds, to tracing immigrant ancestors, to breaking through walls with DNA results, and more. Many of them are included in the Country and Ethnic pages, plus more in the Vault.

Here are a few of the case studies to get you started, in video and article formats (videos noted with their timings):

• ExploreGenealogy: Overcoming a Family History Roadblock
• Family Locket: Hooking Teens on Research with Land Patents
• Family Locket: Putting Your Ancestors in their Place
• BYU FHL: Case Studies in Migration for Genealogists —67:54
• FamilySearch: Using English Records— 16:00
• FamilySearch: A French Case Study: Church Records —5:54
• Ancestry DNA:  Genealogy Brick Wall Case Study —21:26
• The Root: Who Were My Kin Born During Slavery?

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on Facebook (Opens in new window)

Categories: Case Studies ​ Research ​ U.S. Research

Related Posts

Are You Using Google for Family History and Genealogy?

New QRB Video: Beginning Research in Australia

Researching in U.S. Counties

Case Studies: Learning from the Best

Live and Unrehearsed Genealogy Research from Goldie May: Episodes 4 and 5

Where Are the Daughters?

Genealogy Case Studies

• Genealogy Fun
• Vital Records Around the World
• American History
• African American History
• African History
• Ancient History and Culture
• Asian History
• European History
• Latin American History
• Medieval & Renaissance History
• Military History
• The 20th Century
• Women's History
• Certificate in Genealogical Research, Boston University
• B.A., Carnegie Mellon University

As you sift through the records of your own ancestors to build your family tree, you may find yourself with questions:

• What other records can/should I search?
• What else can I learn from this record?
• How do I pull all of these little clues together?

The answers to these types of questions generally come through knowledge and experience. What is so eye-opening about the research of others, especially if the individuals or places in question have nothing to do with your own family? There is no better way to learn (aside from your own hands-on practice) than through the successes, mistakes, and techniques of other genealogists. A genealogical case study can be as simple as an explanation of the discovery and analysis of a particular record, to the research steps taken to trace a particular family back through several generations. Each one, however, gives us a glimpse into research problems that we ourselves may face in our own genealogy searches, approached through the eyes and experience of leaders in the genealogical field.

Genealogical Case Studies

Elizabeth Shown Mills, genealogist, is the author of  Historic Pathways , a website packed with decades of her case studies. Many of the case studies are organized by type of problem—record losses, cluster research, name changes, separating identities, etc.— transcending the place and time of the research, and of value to all genealogists. Read her work and read it often. It will make you a better genealogist.

Some of our favorites include:

• Applying the Preponderance-of-the-Evidence Principle to a Southern Frontier Problem - While "preponderance of the evidence" is no longer used to describe how genealogists analyze and weigh evidence, this is an excellent example of how to document family relationships in situations where no document directly gives the answer.
• The Search for Margaret Ball  - Three "burned counties," repeated name changes, and a pattern of migration through several states stumped genealogists researching Margaret Ball for years until Elizabeth Shown Mills came along to widen the net.
• Unraveling Balls of Yarn: Lessons in the Use of a Skeptical Eye  - We can each learn from the dangers of assuming that previous researchers have carefully avoided renaming individuals, merging identities, or marrying "people to partners they have never met in real life."

Michael John Neill has presented numerous case study examples online over the years. Here are a few of his favorite case studies.

• Fishing for Clues in John Lake's Estate Michael explores what an estate record can tell us even when none of the deceased individual's children are listed.
• Where O Where is Abraham? How a "missing" 1840 census enumeration was right under Michael's nose.
• Turn the Page Learn how three consecutive deeds were analyzed to reveal a potential relationship among the sellers and the buyer.

Juliana Smith brings humor and passion to everything she writes. You can find many of her examples and case studies in her archived Family History Compass column and 24/7 Family History Circle  blog at  Ancestry.com , as well as on the Ancestry.com blog.

• Tips from the Trail of Tobin Hatters  - Juliana uses passenger arrival records, obituaries, and some more unusual records, and stumbles across some startling surprises.
• Straw Goods, Artificial Flowers, and Feathers: Seeking Common Threads in City Directories  - Juliana tackles the daunting task of tracking her Kelly ancestors in New York City directories.

Certified Genealogist Michael Hait has published an ongoing series of genealogical case studies related to his work on the Jefferson Clark family of Leon County, Florida.

More Case Studies

While online case studies provide a wealth of knowledge, many tend to be short and extremely focused. If you're ready to dig in even further, most of the in-depth, complicated genealogical case studies are found published in genealogical society journals and, occasionally, in mainstream genealogy magazines. Good places to start are the  National Genealogical Society Quarterly  (NGSQ) , the  New England Historical and Genealogical Register  (NEHGR) and The American Genealogist . Years of back issues of NGSQ and NEHGR are available online for members of those organizations. A few excellent online examples by authors such as Elizabeth Shown Mills, Kay Haviland Freilich, Thomas W. Jones and Elizabeth Kelley Kerstens, can also be found in the  Sample Work Products  provided online by the Board for Certification of Genealogists.

• Making a Living from Genealogy
• 5 Genealogical Journals You Should Be Reading
• How To Become a Professional Genealogist
• Free Online Genealogy Education Sources
• 10 Educational Opportunities for Genealogists
• How to Prove Your Family Tree Connections
• 10 Steps for Finding Your Family Tree Online
• 12 Free Jewish Genealogy Databases Online
• Discovering the Occupations of Your Ancestors
• Pennsylvania Genealogy Online
• 5 Family History Scams to Avoid
• 10 Genealogy Blogs Worth Reading
• U.S. State Archives Online
• Genealogy Research at the Courthouse, Archives or Library
• Five Steps to Verifying Online Genealogy Sources
• 10 Fabulous Sources for Family History Books Online

• Bipolar Disorder
• Therapy Center
• When To See a Therapist
• Types of Therapy
• Best Online Therapy
• Best Couples Therapy
• Best Family Therapy
• Managing Stress
• Sleep and Dreaming
• Understanding Emotions
• Self-Improvement
• Healthy Relationships
• Student Resources
• Personality Types
• Guided Meditations
• Verywell Mind Insights
• 2024 Verywell Mind 25
• Mental Health in the Classroom
• Editorial Process
• Meet Our Review Board
• Crisis Support

What Is a Case Study?

Weighing the pros and cons of this method of research

Kendra Cherry, MS, is a psychosocial rehabilitation specialist, psychology educator, and author of the "Everything Psychology Book."

Cara Lustik is a fact-checker and copywriter.

Verywell / Colleen Tighe

• Pros and Cons

What Types of Case Studies Are Out There?

Where do you find data for a case study, how do i write a psychology case study.

A case study is an in-depth study of one person, group, or event. In a case study, nearly every aspect of the subject's life and history is analyzed to seek patterns and causes of behavior. Case studies can be used in many different fields, including psychology, medicine, education, anthropology, political science, and social work.

The point of a case study is to learn as much as possible about an individual or group so that the information can be generalized to many others. Unfortunately, case studies tend to be highly subjective, and it is sometimes difficult to generalize results to a larger population.

While case studies focus on a single individual or group, they follow a format similar to other types of psychology writing. If you are writing a case study, we got you—here are some rules of APA format to reference.  

At a Glance

A case study, or an in-depth study of a person, group, or event, can be a useful research tool when used wisely. In many cases, case studies are best used in situations where it would be difficult or impossible for you to conduct an experiment. They are helpful for looking at unique situations and allow researchers to gather a lot of˜ information about a specific individual or group of people. However, it's important to be cautious of any bias we draw from them as they are highly subjective.

What Are the Benefits and Limitations of Case Studies?

A case study can have its strengths and weaknesses. Researchers must consider these pros and cons before deciding if this type of study is appropriate for their needs.

One of the greatest advantages of a case study is that it allows researchers to investigate things that are often difficult or impossible to replicate in a lab. Some other benefits of a case study:

• Allows researchers to capture information on the 'how,' 'what,' and 'why,' of something that's implemented
• Gives researchers the chance to collect information on why one strategy might be chosen over another
• Permits researchers to develop hypotheses that can be explored in experimental research

On the other hand, a case study can have some drawbacks:

• It cannot necessarily be generalized to the larger population
• Cannot demonstrate cause and effect
• It may not be scientifically rigorous
• It can lead to bias

Researchers may choose to perform a case study if they want to explore a unique or recently discovered phenomenon. Through their insights, researchers develop additional ideas and study questions that might be explored in future studies.

It's important to remember that the insights from case studies cannot be used to determine cause-and-effect relationships between variables. However, case studies may be used to develop hypotheses that can then be addressed in experimental research.

Case Study Examples

There have been a number of notable case studies in the history of psychology. Much of  Freud's work and theories were developed through individual case studies. Some great examples of case studies in psychology include:

• Anna O : Anna O. was a pseudonym of a woman named Bertha Pappenheim, a patient of a physician named Josef Breuer. While she was never a patient of Freud's, Freud and Breuer discussed her case extensively. The woman was experiencing symptoms of a condition that was then known as hysteria and found that talking about her problems helped relieve her symptoms. Her case played an important part in the development of talk therapy as an approach to mental health treatment.
• Phineas Gage : Phineas Gage was a railroad employee who experienced a terrible accident in which an explosion sent a metal rod through his skull, damaging important portions of his brain. Gage recovered from his accident but was left with serious changes in both personality and behavior.
• Genie : Genie was a young girl subjected to horrific abuse and isolation. The case study of Genie allowed researchers to study whether language learning was possible, even after missing critical periods for language development. Her case also served as an example of how scientific research may interfere with treatment and lead to further abuse of vulnerable individuals.

Such cases demonstrate how case research can be used to study things that researchers could not replicate in experimental settings. In Genie's case, her horrific abuse denied her the opportunity to learn a language at critical points in her development.

This is clearly not something researchers could ethically replicate, but conducting a case study on Genie allowed researchers to study phenomena that are otherwise impossible to reproduce.

There are a few different types of case studies that psychologists and other researchers might use:

• Collective case studies : These involve studying a group of individuals. Researchers might study a group of people in a certain setting or look at an entire community. For example, psychologists might explore how access to resources in a community has affected the collective mental well-being of those who live there.
• Descriptive case studies : These involve starting with a descriptive theory. The subjects are then observed, and the information gathered is compared to the pre-existing theory.
• Explanatory case studies : These   are often used to do causal investigations. In other words, researchers are interested in looking at factors that may have caused certain things to occur.
• Exploratory case studies : These are sometimes used as a prelude to further, more in-depth research. This allows researchers to gather more information before developing their research questions and hypotheses .
• Instrumental case studies : These occur when the individual or group allows researchers to understand more than what is initially obvious to observers.
• Intrinsic case studies : This type of case study is when the researcher has a personal interest in the case. Jean Piaget's observations of his own children are good examples of how an intrinsic case study can contribute to the development of a psychological theory.

The three main case study types often used are intrinsic, instrumental, and collective. Intrinsic case studies are useful for learning about unique cases. Instrumental case studies help look at an individual to learn more about a broader issue. A collective case study can be useful for looking at several cases simultaneously.

The type of case study that psychology researchers use depends on the unique characteristics of the situation and the case itself.

There are a number of different sources and methods that researchers can use to gather information about an individual or group. Six major sources that have been identified by researchers are:

• Archival records : Census records, survey records, and name lists are examples of archival records.
• Direct observation : This strategy involves observing the subject, often in a natural setting . While an individual observer is sometimes used, it is more common to utilize a group of observers.
• Documents : Letters, newspaper articles, administrative records, etc., are the types of documents often used as sources.
• Interviews : Interviews are one of the most important methods for gathering information in case studies. An interview can involve structured survey questions or more open-ended questions.
• Participant observation : When the researcher serves as a participant in events and observes the actions and outcomes, it is called participant observation.
• Physical artifacts : Tools, objects, instruments, and other artifacts are often observed during a direct observation of the subject.

If you have been directed to write a case study for a psychology course, be sure to check with your instructor for any specific guidelines you need to follow. If you are writing your case study for a professional publication, check with the publisher for their specific guidelines for submitting a case study.

Here is a general outline of what should be included in a case study.

Section 1: A Case History

This section will have the following structure and content:

Background information : The first section of your paper will present your client's background. Include factors such as age, gender, work, health status, family mental health history, family and social relationships, drug and alcohol history, life difficulties, goals, and coping skills and weaknesses.

Description of the presenting problem : In the next section of your case study, you will describe the problem or symptoms that the client presented with.

Describe any physical, emotional, or sensory symptoms reported by the client. Thoughts, feelings, and perceptions related to the symptoms should also be noted. Any screening or diagnostic assessments that are used should also be described in detail and all scores reported.

Your diagnosis : Provide your diagnosis and give the appropriate Diagnostic and Statistical Manual code. Explain how you reached your diagnosis, how the client's symptoms fit the diagnostic criteria for the disorder(s), or any possible difficulties in reaching a diagnosis.

Section 2: Treatment Plan

This portion of the paper will address the chosen treatment for the condition. This might also include the theoretical basis for the chosen treatment or any other evidence that might exist to support why this approach was chosen.

• Cognitive behavioral approach : Explain how a cognitive behavioral therapist would approach treatment. Offer background information on cognitive behavioral therapy and describe the treatment sessions, client response, and outcome of this type of treatment. Make note of any difficulties or successes encountered by your client during treatment.
• Humanistic approach : Describe a humanistic approach that could be used to treat your client, such as client-centered therapy . Provide information on the type of treatment you chose, the client's reaction to the treatment, and the end result of this approach. Explain why the treatment was successful or unsuccessful.
• Psychoanalytic approach : Describe how a psychoanalytic therapist would view the client's problem. Provide some background on the psychoanalytic approach and cite relevant references. Explain how psychoanalytic therapy would be used to treat the client, how the client would respond to therapy, and the effectiveness of this treatment approach.
• Pharmacological approach : If treatment primarily involves the use of medications, explain which medications were used and why. Provide background on the effectiveness of these medications and how monotherapy may compare with an approach that combines medications with therapy or other treatments.

This section of a case study should also include information about the treatment goals, process, and outcomes.

When you are writing a case study, you should also include a section where you discuss the case study itself, including the strengths and limitiations of the study. You should note how the findings of your case study might support previous research. 

In your discussion section, you should also describe some of the implications of your case study. What ideas or findings might require further exploration? How might researchers go about exploring some of these questions in additional studies?

Need More Tips?

Here are a few additional pointers to keep in mind when formatting your case study:

• Never refer to the subject of your case study as "the client." Instead, use their name or a pseudonym.
• Read examples of case studies to gain an idea about the style and format.
• Remember to use APA format when citing references .

Crowe S, Cresswell K, Robertson A, Huby G, Avery A, Sheikh A. The case study approach .  BMC Med Res Methodol . 2011;11:100.

Crowe S, Cresswell K, Robertson A, Huby G, Avery A, Sheikh A. The case study approach . BMC Med Res Methodol . 2011 Jun 27;11:100. doi:10.1186/1471-2288-11-100

Gagnon, Yves-Chantal.  The Case Study as Research Method: A Practical Handbook . Canada, Chicago Review Press Incorporated DBA Independent Pub Group, 2010.

Yin, Robert K. Case Study Research and Applications: Design and Methods . United States, SAGE Publications, 2017.

By Kendra Cherry, MSEd Kendra Cherry, MS, is a psychosocial rehabilitation specialist, psychology educator, and author of the "Everything Psychology Book."

An official website of the United States government

Here’s how you know

Official websites use .gov A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS A lock ( Lock Locked padlock icon ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

• Health Topics
• Drugs & Supplements
• Medical Tests
• Medical Encyclopedia
• About MedlinePlus
• Customer Support
• Why is it important to know my family health history?

A family health history is a record of health information about a person and his or her close relatives. A complete record includes information from three generations of relatives, including children, brothers and sisters, parents, aunts and uncles, nieces and nephews, grandparents, and cousins.

Families have similar genetic backgrounds, and often similar environments and lifestyles. Together, these factors can give clues to conditions that may run in a family . By noticing patterns of disorders among relatives, healthcare professionals can determine whether an individual, family members, or future generations may be at an increased risk of developing a particular condition.

A family health history can identify people with a higher-than-usual chance of having common disorders, such as heart disease, high blood pressure , stroke, certain cancers, and type 2 diabetes. These complex disorders are influenced by a combination of genetic factors, environmental conditions, and lifestyle choices. A family history also can provide information about the risk of rarer conditions caused by variants (mutations) in a single gene, such as cystic fibrosis and sickle cell disease .

While a family health history provides information about the risk of specific health concerns, having relatives with a condition does not mean that an individual will definitely develop that condition. On the other hand, a person with no family history of a disorder may still be at risk of developing the disorder.

Knowing one’s family health history allows a person to take steps to reduce his or her risk. For people at an increased risk of certain cancers, healthcare professionals may recommend more frequent screening (such as mammography or colonoscopy) starting at an earlier age. Healthcare providers may also encourage regular checkups or testing for people with a condition that runs in their family. Additionally, lifestyle changes such as adopting a healthier diet, getting regular exercise, and quitting smoking help many people lower their chances of developing heart disease and other common illnesses.

The easiest way to get information about family health history is to talk to relatives about their health. Have they had any health problems, and when did they occur? A family gathering could be a good time to discuss these issues. Additionally, obtaining medical records and other documents (such as obituaries and death certificates) can help complete a family health history. It is important to keep this information up-to-date and to share it with a healthcare professional regularly.

Topics in the Inheriting Genetic Conditions chapter

• What does it mean if a disorder seems to run in my family?
• What are the different ways a genetic condition can be inherited?
• If a genetic disorder runs in my family, what are the chances that my children will have the condition?
• What are reduced penetrance and variable expressivity?
• What do geneticists mean by anticipation?
• What are genomic imprinting and uniparental disomy?
• Are chromosomal disorders inherited?
• Why are some genetic conditions more common in particular ethnic groups?
• What is heritability?

Other chapters in Help Me Understand Genetics

Genetics Home Reference has merged with MedlinePlus. Genetics Home Reference content now can be found in the "Genetics" section of MedlinePlus. Learn more

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.

• Introduction to Genomics
• Educational Resources
• Policy Issues in Genomics
• The Human Genome Project
• Funding Opportunities
• Funded Programs & Projects
• Division and Program Directors
• Scientific Program Analysts
• Contact by Research Area
• News & Events
• Research Areas
• Research investigators
• Research Projects
• Clinical Research
• Data Tools & Resources
• Genomics & Medicine
• Family Health History
• For Patients & Families
• For Health Professionals
• Jobs at NHGRI
• Training at NHGRI
• Funding for Research Training
• Professional Development Programs
• NHGRI Culture
• Social Media
• Broadcast Media
• Image Gallery
• Press Resources
• Organization
• NHGRI Director
• Mission & Vision
• Policies & Guidance
• Institute Advisors
• Strategic Vision
• Leadership Initiatives
• Diversity, Equity, and Inclusion
• Partner with NHGRI
• Staff Search

Family Health History for Healthcare Professionals

Family health history is a record of the diseases and health conditions in your family. Knowing the health history of your family members can help you and your healthcare providers determine how to manage your health and the health of your family. 

Family Health History Group

The Family Health History Group connects stakeholders, researchers, and thought leaders to share learning, understand barriers in depth, and discuss issues and potential solutions related to the collection of family health history information. Multi-disciplinary, volunteer members come from government, industry, health care, research, advocacy and policy backgrounds, and represent many countries. Members meet regularly by teleconference. Contact:  [email protected].

My Family Health Portrait (MFHP) - This web-based tool creates a family pedigree with health information for patients and their providers to identify patterns of inheritance and identify risk factors.

The NHGRI Family Health History Tool Conference June 13-14, 2016

Case Studies

Mitochondrial DNA mutation A1555G and aminoglycoside-induced hearing loss and deafness Type of Case Study: Gene-Based Intervention for Aminoglycoside Sensitivity Pharmacogenomics/Family History. In collaboration with American Academy of Pediatrics and the American Academy of Otolaryngology-Head and Neck Surgery  

Utilizing family history to identify Lynch Syndrome Type of Case Study: Family History In collaboration with the National Cancer Institute

Last updated: January 6, 2023

Case Study: High Lipoprotein(a) Levels in Younger Patients Are Not So Clear Cut

"Medical Journeys" is a set of clinical resources reviewed by doctors, meant for physicians and other healthcare professionals as well as the patients they serve. Each episode of this journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

This month: A noteworthy case study.

What preventive measures could be recommended to a man in his early 40s looking to reduce his cardiovascular risk, given his strong family history of premature cardiovascular events?

That's what Anandita Agarwala, MD, of Baylor Scott & White The Heart Hospital–Plano in Texas, and colleagues had to decide when the man presented for advice based on his level of cardiovascular risk.

As the team detailed in a clinical challenge in JAMA Cardiology , the patient, who was of South Asian ancestry, had no symptoms or traditional risk factors for atherosclerotic cardiovascular disease (ASCVD), was physically active, had never smoked, and did not take any medications .

He did, however, have a concerning family history of premature cardiovascular events: Specifically, his older brother at age 43 had undergone angioplasty with placement of several stents, his father had a heart attack at age 39, and several male paternal cousins had coronary artery disease.

Clinicians estimated that the patient's personal 10-year ASCVD risk was low (1.6%), based on the pooled cohort equations (PCEs). He was, however, at increased CV risk related to his South Asian ancestry and his family history of premature ASCVD.

The medical team, therefore, ordered screening for elevated lipoprotein(a) -- Lp(a) -- and assessed his coronary calcium score. "His Lp(a) level was elevated at 136 nmol/L and his coronary calcium score of 137 Agatston units was notable and placed him in the 94th percentile for his age," Agarwala and co-authors reported.

The patient returned to the medical office later in the day and received counseling on how best to address the findings.

The optimum approach and next steps include, the case authors said:

• Address all modifiable cardiovascular risk factors
• Perform cascade screening of the patient's first- and second-degree family members
• Initiate high-intensity statin therapy and aspirin, 81 mg, daily

Lipoprotein(a) -- Lp(a) -- is proatherogenic, prothrombotic, and proinflammatory, and has a prevalence of about 20% worldwide, Agarwala and colleagues noted, adding that Lp(a) values that define an elevated ASCVD risk vary, but anything above the 80th (100 nmol/L) or 85th (125 nmol/L) percentile are clinically accepted as falling into the category.

"Elevated Lp(a) is actionable," the team said, noting that various lipid-lowering therapies are currently being studied . This patient's elevated Lp(a) level raised particular concern because of the preexisting risk factors of family history of premature atherosclerotic heart disease and his South Asian ancestry. Thus, although his 10-year risk as calculated in pooled cohort equations was low, the presence of three or more risk-enhancing factors (REFs) may incrementally increase ASCVD risk beyond the PCE estimates.

In the setting of a family history of premature ASCVD, results of PCE-based risk assessment may be too low to warrant consideration, which "points to a unique use of the REFs," the case authors said.

They advised that improving clinical management for this patient should include:

• Lifestyle counseling -- for example, with the American Heart Association's " Life's Essential 8 "
• Assessment of coronary artery calcium (CAC) to guide medical treatment
• Familial cascade screening -- i.e., first-degree family members, and second-degree family members with relevant family history

When helping patients understand how high levels of Lp(a) can affect ASCVD disease, comprehensive treatment of all modifiable ASCVD risk factors is key, Agarwala and co-authors said.

They added that even though Lp(a) levels cannot be lowered by treating risk factors, managing those that are modifiable can reduce an individual's overall ASCVD risk. In fact, this risk can be reduced significantly by making the lifestyle changes in Life's Essential 8.

Scoring of CAC is important to guide treatment options, when a risk decision for statin therapy is not clear, the case authors noted. In their patient, they said, his family history and elevated Lp(a) level provide sufficient support for the use of statin therapy, and a significantly elevated CAC score may justify a more aggressive treatment approach with lipid-lowering medications and aspirin.

While elevated levels of CAC and Lp(a) each play an independent role in the CV risks faced by these patients, PCSK9 inhibitors can lower Lp(a) by 15-25%, the authors said. Comparatively, the most efficient approach to addressing individual risk of ASCVD is to reduce levels of low-density lipoprotein cholesterol (LDL-C), as this offers a greater ASCVD risk reduction per mmol/L.

The case authors said that given that approximately 80-90% of an individual's Lp(a) level is genetically determined in an autosomal codominant inheritance pattern, the team recommends cascade screening – which was offered to relatives of this particular patient – as a high-yield way to identify first-degree relatives who carry the abnormal trait.

The authors said this case highlights the complexities of managing elevated Lp(a) in younger patients, since their young age may artificially reduce the 10-year ASCVD risk calculated using PCE. An LDL-C level of 160-189 mg/dL and a family history of premature ASCVD can help identify people likely to have familial hypercholesterolemia, as in this patient whose ethnicity further contributes to an increased ASCVD risk.

"Although this should be addressed by future guidelines, we believe that together these high-risk, long-term personal traits merit an intensive LDL-C and apolipoprotein B–lowering regimen," Agarwala and co-authors concluded.

Read previous installments in this series:

Part 1: Hypercholesterolemia: A Complex System

Part 2: Consequences of Hypercholesterolemia

Part 3: Genetics of Hypercholesterolemia

Agarwala reported no conflicts of interests; co-authors reported various relationships with industry.

Maker of weight loss drug Ozempic plans to study drug’s effects on alcohol consumption

(CNN) – People on the weight loss drug Ozempic say they’ve experienced an unexpected effect: a lessened desire to drink alcohol.

The feeling has been described by thousands of people taking medicines, which are in a class known as GLP-1 receptor agonists.

Ozempic’s maker, Novo Nordisk, said it intends to study the phenomenon, although cutting the drinking isn’t the study’s main goal.

The company plans to start assessing the effects of semaglutide, the active ingredient in Ozempic and other medicines, on alcohol consumption in a newly announced clinical trial on alcohol-related liver disease.

The trial aims to enroll about 240 participants and is stated to begin May 20.

Experts said treatment options for people with alcoholism and liver disease are needed.

Copyright 2024 CNN Newsource. All rights reserved.

17-year-old arrested in Gulfport double homicide

Cold Case: Hurricane Katrina victim identified nearly two decades later

Reports of weapon, bombs on campus lead to evacuation of West Harrison schools

First Alert: Multiple rounds of thunderstorms Friday into Saturday

CLEARED: Missing Gautier woman found safe, officials say

Latest news.

GOP advances Garland contempt charges after White House exerts executive privilege over Biden audio

Severe storms kill at least 4 in Houston, knock out power to 850,000 homes and businesses

Lainey Wilson wins big at the 2024 Academy of Country Music Awards, including the top honor

Tree falls on car in Harris County, Texas

Caught on camera: Power line sparks in severe weather

A protocol to assess risk of fractures associated with use of menopausal hormone therapy: nested case-control study using CPRD

• Find this author on Google Scholar
• Find this author on PubMed
• Search for this author on this site
• ORCID record for Yana Vinogradova
• For correspondence: [email protected]
• ORCID record for Barbara Iyen
• ORCID record for Tahir Masud
• ORCID record for Joe Kai
• Info/History
• Preview PDF

Menopausal hormone therapy (MHT) is prescribed to women with severe symptoms of menopause. Various studies have demonstrated increased bone density and decreased fracture risk in women using MHT. The randomised controlled trials were, however, run over only relatively short time periods, and there is no reliable or consistent evidence about fracture risk after MHT discontinuation. The proposed nested case-control study aims to fill this gap. We will use CPRD (GOLD and AURUM) and HES data. Every woman 40 years or over with a diagnosis of first fracture between 1998 and 2022 (a case) will be matched by age and general practice to up to 5 female controls with no previous records of fracture at the time of the case diagnosis (index date). MHT exposure will be assessed using prescriptions for the different types of MHT treatment historically available from the NHS. Conditional logistic regression will estimate fracture risk associated with duration of use and gap after discontinuation of MHT. The findings will be adjusted for smoking status, body mass index, family history of dementia, medical conditions and events, other medications and contraceptive drugs. A number of sensitivity analyses will be run to address the limitations of the study.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study was funded by School for Primary Care Research NIHR, #617

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

National Research Ethics Service Committee (NRES), for all purely observational research using anonymised CPRD data, eRap#22_002376

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Data Availability

To guarantee the confidentiality of personal and health information, only the authors can have access to the CPRD data during the study in accordance with the relevant licence agreements. CPRD linked data were provided under a licence that does not permit sharing.

View the discussion thread.

Thank you for your interest in spreading the word about medRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Citation Manager Formats

• EndNote (tagged)
• EndNote 8 (xml)
• RefWorks Tagged
• Ref Manager
• Tweet Widget
• Facebook Like
• Google Plus One
• Addiction Medicine (324)
• Allergy and Immunology (627)
• Anesthesia (163)
• Cardiovascular Medicine (2371)
• Dentistry and Oral Medicine (289)
• Dermatology (206)
• Emergency Medicine (379)
• Endocrinology (including Diabetes Mellitus and Metabolic Disease) (836)
• Epidemiology (11768)
• Forensic Medicine (10)
• Gastroenterology (702)
• Genetic and Genomic Medicine (3736)
• Geriatric Medicine (350)
• Health Economics (633)
• Health Informatics (2395)
• Health Policy (932)
• Health Systems and Quality Improvement (896)
• Hematology (341)
• HIV/AIDS (782)
• Infectious Diseases (except HIV/AIDS) (13308)
• Intensive Care and Critical Care Medicine (767)
• Medical Education (365)
• Medical Ethics (104)
• Nephrology (398)
• Neurology (3501)
• Nursing (198)
• Nutrition (524)
• Obstetrics and Gynecology (674)
• Occupational and Environmental Health (663)
• Oncology (1823)
• Ophthalmology (537)
• Orthopedics (218)
• Otolaryngology (287)
• Pain Medicine (232)
• Palliative Medicine (66)
• Pathology (446)
• Pediatrics (1033)
• Pharmacology and Therapeutics (426)
• Primary Care Research (420)
• Psychiatry and Clinical Psychology (3175)
• Public and Global Health (6138)
• Radiology and Imaging (1280)
• Rehabilitation Medicine and Physical Therapy (747)
• Respiratory Medicine (826)
• Rheumatology (379)
• Sexual and Reproductive Health (372)
• Sports Medicine (323)
• Surgery (402)
• Toxicology (50)
• Transplantation (172)
• Urology (145)

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List
• v.58; Jan-Dec 2021

Family History of Psychiatric Disorders and Clinical Factors Associated With a Schizophrenia Diagnosis

Lina díaz-castro.

1 Research in Medical Sciences, Direction of Epidemiological and Psychosocial Research, National Institute of Psychiatry Ramon de la Fuente Muñiz, Mexico City, Mexico

Kurt Hoffman

2 Carlos Beyer Center for Investigation of Animal Reproduction (CIRA), Autonomous University of Tlaxcala and Center for Investigation and Advanced Studies of the National Polytechnical Institute (UATx - CINVESTAV), Tlaxcala, Mexico

Héctor Cabello-Rangel

3 Research in Health Systems, Diagnostic Auxiliary Division, Psychiatric Hospital Fray Bernardino Álvarez, Mexico City, Mexico

Armando Arredondo

4 Research in Medical Sciences, Health Systems Research Center, National Institute of Public Health, Cuernavaca, Mexico

Miguel Ángel Herrera-Estrella

5 Medical Doctor, Hospitalization Services, Psychiatric Hospital Fray Bernardino Álvarez, Mexico City, Mexico

Schizophrenia (SCH) and bipolar disorder (BD) have both shared and unique genetic risk factors and clinical characteristics. The aim of the present study was to identify potential risk factors significantly associated with SCH, relative to a BD reference group.

Data were obtained from medical records of patients that entered a major Mexico City hospital during 2009–2010 presenting psychotic symptoms (n = 1132; 830 cases of SCH, 302 cases of BD; 714 men and 418 women). SCH and BD diagnoses were compared with respect to a number of family and clinical characteristics. Logistic and linear regression analyses were used to respectively identify factors selectively associated with the SCH diagnosis relative to the BD diagnosis and explore the relationship between PANSS scores and parental age at time of birth to the age of SCH onset.

Patients with SCH showed greater functional impairment than those with BD. Family history of mental illness, premorbid schizoid-like personality, and obstetric trauma were significantly associated with the SCH diagnosis. The association of obstetric trauma with SCH was greatest in male patients with a family history of mental illness. In women, increased paternal and decreased maternal age at time of the patient’s birth were associated with an earlier age of SCH onset.

Male gender, showing premorbid schizoid-like personality, familial SCH, and obstetric trauma are risk factors that distinguish SCH from BD. Additionally, our results suggest that risk for SCH relative to BD may be importantly influenced by interactions between familial risk, gender, and obstetric trauma.

1. What do we already know about this topic?

Schizophrenia (SCH) and bipolar disorder (BD) share a number of genetic liability factors and clinical characteristics; yet, each also has distinct genetic liability factors and distinct diagnostic characteristics. Environmental factors such as childhood trauma, obstetric trauma, maternal infections during pregnancy as well as biological or psychological factors influence the presentation of schizophrenia, depression, or BD.

2. How does your research contribute to the field?

The results of the present study corroborate a number of published findings, including the association of family history of mental illness, obstetric trauma, and premorbid personality characteristics with SCH. However, our study further associates these factors with SCH relative to a BD diagnosis, suggesting that these factors may participate more specifically in the pathogenesis of SCH relative to other psychotic disorders (e.g., BD). Our study also suggests important interactions between genetic liability, gender, and obstetric trauma that are associated with the SCH diagnosis.

3. What are your research’s implications towards theory, practice, or policy?

With regards to neurodevelopmental theories for the pathogenesis of psychotic disorders, the present results suggest important gene by sex by environment interactions that may be specific to the pathogenesis of SCH, relative to BD. These possible interactions require further investigation within epidemiological and translational/neurobiological contexts. With regards to clinical practice, the present results corroborate a large body of published work that has associated specific factors with increased risk for SCH; such factors should be considered in the clinical treatment of youth, in order to devise and apply strategies aimed at prevention and early detection of SCH.

Introduction

Clinical descriptions of schizophrenia (SCH) have been the subject of several publications since 1899, and the current diagnostic criteria for SCH reflect the main clinical features of the disorder as described historically by diagnostic experts. 1 Traditionally, BD has been considered a clinical entity distinct from SCH; yet, the validity of this distinction has been consistently questioned. 2 SCH and BD are associated with unique and shared genetic susceptibility factors, and the final diagnostic manifestation of psychotic disease most likely depends on the interaction between specific environmental factors and these shared and unique genetic factors 2 – 4 Thus, having a parent with a mental disorder increases the risk that the individual will suffer from mental illness, compared to individuals of healthy parents, 5 and risk of familial transmission further varies according the particular family member affected (e.g., mother or father), as well as the sex of the individual. 6

Indeed, interactions between genetic vulnerability and gender can modify pathogenesis of mental illness. Published studies related to the family risk of suffering SCH are contradictory; some find no association between age, gender and family risk, 7 while others have reported higher risk in siblings of male patients who had early onset of the disease. 8 It has been suggested that women may require a higher presence of family risk of SCH, compared to men, to develop the disease. 9

Finally, various environmental factors such as childhood trauma, infectious agents, and obstetric complications have been associated with a range of psychiatric disorders, including SCH and BD. 10 , 11 These risk factors can be biological, physical, psychological or social, and may operate at different times in the life of the affected individual (fetal period, childhood, adolescence, and early adulthood). Moreover, several risk factors associated with childhood and adolescence can predict the age of onset of psychosis in patients, either with or without the component of familial vulnerability (SD). 12 Thus, the ultimate diagnostic manifestation of psychotic illness most likely is determined by a complex interaction of underlying genetic vulnerability, sex of the individual, and a variety of environmental and social factors.

Among the clinical characteristics associated with SCH, age of onset is an important variable in determining the expression and course of disease. 13 An early age of onset of psychosis is associated with more psychopathology 14 increased cognitive impairment, 15 previous behavioral problems 16 and premorbid personality changes. 17 Moreover, patients with earlier onset often have unfavorable risk factors, such as a long duration of untreated psychosis, premorbid personality, and higher rates of substance use. 18 Identifying predictive factors and elucidating the underlying mechanisms of psychosis onset are fundamental for facilitating the clinical evolution and functional improvement of patients with SCH.

The BD and SCH diagnoses are among the most prevalent in inpatient psychiatric healthcare, and are the most well studied with respect to genetic liability. These disorders share genetic vulnerability, have a similar symptomatology and chronic clinical course, but they differ importantly in the degree of their neuropsychological effects and social repercussions. The aim our study was to identify family and clinical factors that were associated with a SCH diagnosis relative to a reference group with a BD diagnosis, and explore the possibility that gender might modify the effects of these factors. We also examined the effects of PANSS positive and negative scores and parental age at the time of the patient’s birth, on the age of first psychotic episode.

Material and Methods

The present study was carried out in the largest public psychiatric hospital in Mexico City. The data for the analysis were collected from a database derived from medical records, and includes a large sample (n = 1040) of patients treated from 2009 until 2010. The data collected were strictly anonymous and confidential.

Study Assessments

The medical records included data on psychiatric diagnosis according to Structured Clinical Interview for DSM-IV. Other data that were collected during the interview with the patient and his/her caregiver, and that were analyzed in the present study were: (1) functional indicators including relationship status (having or not a long-term stable relationship), maximum education level, and employment; (2) familial indicators including family history of mental illness, family member diagnosed with mental illness, specific mental illness of family member, age of father, and age of mother at the time of the patient’s birth; (3) personal and clinical data of the patient, including comorbid conditions (obesity, diabetes, and others), alcoholism, drug abuse, smoking, obstetric trauma associated with the patient’s birth (as reported retrospectively by the patient’s mother), and if the patient had been breastfed as an infant; and (4) indicators of disease severity including age of first psychotic episode, PANSS positive and PANSS negative symptom scores, and course of illness (a single psychotic episode, multiple psychotic episodes, or continuous psychosis).

Statistical Analysis

Descriptive and inferential analyses.

Frequencies and proportions were analyzed using the Chi2 and Fisher’s Exact test. Means were compared using the Student’s t-test.

Binary Logistic regression

We created a series of logistic regression models with the dependent variable “diagnosis” (SCH = 1, with the reference category being BD = 0), in order to identify factors that were significantly and specifically associated with the SCH diagnosis, relative to the BD diagnosis (the latter being assigned as the reference category). The following explanatory variables were entered into the logistic regression analysis in a single step: sex (male, female; female = reference category), family history of mental disorders (yes or no; no = reference category), type of familial history of mental disorders (none, SCH, BD, or depression), family member with mental disorder (father, mother, sibling, and others), obstetric trauma associated with the patient’s birth (yes or no, as reported retrospectively by the mother of the patient; no = reference category), having been breastfed as an infant (yes or no; yes = reference category), premorbid personality characteristics (yes or no; no = reference category; examples of premorbid characteristics, and relationship status (yes or no; yes = reference category). These explanatory variables were chosen based on existing evidence in the published literature. 19 – 21

Multiple Linear Regressions

Linear regression was carried out considering age of the first psychotic episode as the outcome variable and PANSS negative scores, PANSS positive scores, and the age of the father and age of the mother at the time of the patient’s birth as predictors. All predictor variables were entered as a single step. For all statistical analyses we used the software SPSS Version 25.

Comparisons Between SCH and BD

First, we compared patients diagnosed with SCH and patients diagnosed with BD, with respect to a number of variables of interest ( Table 1 ). Patients with SCH were significantly less often in a long-term stable relationship compared to those with BD, and also differed significantly with respect to educational level and occupation. With regards to maximum education level achieved, patients with SCH more often reported secondary school as their maximal level of education, while those with BD more often reported enrolling in or completing post-secondary professional degree (technical school or university level). Patients with SCH were more likely to be unemployed, while patients with BD more often reported working within the home.

Comparison of the Schizophrenia (SCH) and Bipolar Disorder (BD) Diagnoses.

Mean years (age of patient; maternal and paternal age) or percentages are shown, with number of cases in parentheses. Student’s T-tests were used to compare ages, all other comparisons were by the Chi2 test ( X 2 ). Statistical significance was assumed at P < .05; ns: non-significant comparisons.

There was no difference between the SCH and BD diagnoses with regards to the proportions of patients that reported having a family history of mental disorder; however, SCH and BD patient groups differed with respect to type of familial disorder and the specific family member affected. Thus, patients with BD more often reported that their mother suffered from a mental disorder compared to patients with SCH, and more often reported a family history of BD. By contrast, patients with SCH more often reported a family history of SCH. SCH and BD patient groups also differed significantly with respect to premorbid (i.e., present before onset of illness) personality characteristics. Specifically, premorbid schizoid characteristics were reported significantly more often in patients with SCH compared to those with BD.

The age of the parents at the time of the patient’s birth did not differ between SCH and BD patient groups, nor did these groups differ with respect to the likelihood of being breastfed as infants. However, patients with SCH more often reported that their birth was associated with obstetric trauma.

Comparisons Between Male and Female Patient Groups

Male and female patients differed significantly with respect to certain clinical characteristics associated with the SCH and BD diagnoses ( Table 2 ). With regards to the SCH diagnosis, men had a significantly earlier age of first psychotic episode, showed higher PANSS negative and PANSS total scores, and more often suffered from comorbid substance abuse, alcoholism and smoking. Women with SCH were significantly more likely than men to suffer from comorbid obesity (8.5% of women, compared to 1.4% of men; data not shown) or tardive dyskinesia (4.3% of women, compared to .7% of men; data not shown). Considering the BP diagnosis, male patients differed significantly from females in that they more often were smokers, or suffered from substance abuse or alcoholism. Men and women of either SCH or BD diagnoses did not differ with respect to the chronicity of psychosis (i.e., a single psychotic episode, multiple psychotic episodes, or continuous psychosis).

Comparisons Between Male and Female Patients Diagnosed With Schizophrenia or Bipolar Disorder.

Mean, standard deviation (SD), and sample sizes are shown for age of patient, PANSS scores, and duration of disease, and comparisons were done by the Student’s T-test. Proportions and corresponding percentages are shown for all other variables; statistical comparisons were done by the Chi2 test ( X 2 ). Asterisks denote statistical significance at P < .05 (*) and P < .01 (**).

Binary Logistic Regression

The initial logistic regression model comprised 560 cases (481 cases of SCH, 79 cases of BD; 386 men, 174 women); 480 cases could not be included due to missing data. This model was significant (Chi2 = 134.33, P=.000; Nagelkerke R2 = .383), and correctly predicted 87.1% of the cases of SCH. Statistically significant individual predictors were: a positive family history of a mental disorder (OR = 160.34), the presence of premorbid personality characteristics (OR = 4.98), the familial relationship (father, mother, brother, grandparent, and other) of the affected family member to the patient (OR = 1.82) and the type of familial mental disorder (OR = 5.80). Having a stable long-term relationship was a significant negative predictor (OR = .26). Given the body of published literature that has associated obstetric trauma with SCH, we tested 3 further models in order to examine the possibility that obstetric trauma might interact with genetic liability (i.e., family history of mental illness) and/or gender ( Table 3 ).

Logistic Regression: Factors Associated With a Schizophrenia Diagnosis.

Logistic regression considering diagnosis as the outcome variable (BD vs SCH; BD as reference category). S.E. = Standard Error. Sig. = Significance (One-tailed P value). C. I. = Confidence Intervals. Family history (yes or no; reference category: no). Family member affected (father, mother, siblings, others, nobody; reference category: nobody)). Type of familial mental disorder (schizophrenia, bipolar disorder, depression, others, none; reference category: none). Obstetric trauma during birth (yes or no; reference category: no). Breastfeeding (yes or no; reference category: no). Premorbid personality (yes or no; reference category: no). With a relationship (yes or no; reference category: no). Sex (female or male; reference category: female).

The first model incorporated only those patients with a family history of mental disorders . There were 263 such cases included in this analysis (231 cases of SCH, 32 cases of BD); 210 cases were omitted due to missing data. The resulting model was significant (Ch2 = 88.3; P = .000; Nagelkerke R2 = .55), and correctly predicted 89.4% of the cases of SCH. Significant positive predictors were being male (OR = 3.34) and obstetric trauma (OR = 3.81), type of familial psychiatric disorder (OR = 6.53), and family member with psychiatric disorder (OR = 1.98). Having a stable long-term relationship (.17) was a significant negative predictor ( Table 4 ).

Logistic Regression: Factors Associated With a Schizophrenia Diagnosis in Patients Having a Positive Family History of Mental Illness.

Logistic regression considering diagnosis as the outcome variable (BD vs SCH; BD as reference category), only cases that had a positive family history of mental disorder were entered into the analysis. S.E. = Standard Error. Sig. = Significance (One-tailed P value). C. I. = Confidence Intervals. Family member affected (father, mother, siblings, others, nobody; reference category: nobody)). Type of familial mental disorder (schizophrenia, bipolar disorder, depression, others, none; reference category: none). Obstetric trauma during birth (yes or no; reference category: no). Breastfeeding (yes or no; reference category: no). Premorbid personality (yes or no; reference category: no). With a relationship (yes or no; reference category: no). Sex (female or male; reference category: female).

The second model considered these same predictors, but male and female cohorts were analyzed separately . With regards to the male patient group (186 cases: 172 cases of SCH, 14 cases of BD; 109 cases omitted due to missing data) the model was significant (Chi2 = 46.00; P = .000; Nagelkerke R2 = .53), and correctly predicted 91% of the cases of SCH. The only significant positive predictor in this model was obstetric trauma (OR = 19.33). Family member with psychiatric illness (OR = .27) and type of familial mental illness (OR = .14), and having a stable long-term relationship (OR =.014) remained significant negative predictors. Having premorbid personality characteristics was not a significant predictor in this model. This same analysis of women patients (18 cases of SCH, 59 cases of BD; 102 cases omitted due to missing data) was also significant (Chi2 = 41.20; Nagelkerke R2 = .63) and correctly predicted 70.1% of cases. However, this model showed only 1 significant negative predictor of a small effect size: family member with psychiatric illness (OR = .056).

A final model considered only cases in which there was no family history of a mental disorder . This analysis included 297 cases (250 cases of SCH, 49 cases of BD; 200 men, 97 women); 250 cases were omitted due to missing data. The resulting model was significant (Chi2 = 54.3, P = .000; Nagelkerke R2 = .28), and correctly predicted 83.6% of the cases of SCH. Significant positive predictors were being male (OR = 2.42) and the presence of premorbid personality characteristics (OR = 7.32). Having a stable long-term relationship was negatively associated with the SCH diagnosis (OR = .27). Notably, obstetric trauma did not emerge as a significant predictor in this model.

Multiple Linear Regression

We used linear regression to model predictor variables for 1 indicator of SCH severity: age of first psychotic episode. Predictor variables were: age of father at the birth of the patient, age of mother at the birth of the patient, PANSS positive symptom scores, and PANSS negative symptom scores. Three regression analyses were carried out: the first considered all patients with SCH (n = 669 cases), the second considered only male patients with SCH (n = 477), and the third considered female patients with SCH2 (n = 192). The first model was significant (B = 29.0; t = 16.71; P = .000), and predicted 5.8% of the variance in age of first psychotic episode (adjusted R2 = .058). Father’s age (B = .128; t = 2.29, P = .022) was positively associated with the age of first psychotic episode, while PANSS positive score (B = −1.369; t = −4.43; P = .000) and PANSS negative score (B = −.903; t = −2.57; P = .01) were significant negative predictors. The second model, considering only men with a SCH diagnosis, was also significant (B = 26.08; t = 13.37; P = .000), and explained 4.3% of the variance in the dependent variable (adjusted R2 = .043). PANSS positive symptom score was the only statistically significant negative predictor (B = −1.50; t = −4.33; P = .000). The third model, which considered only women with SCH, explained 9.0% of the variance in the dependent variable (adjusted R2 = .09). All 4 predictor variables were statistically significant ( Table 5 ). Thus, in women patients, having an older father, a younger mother, higher positive PANSS scores, and higher negative PANSS scores were each significant predictors of an earlier age of psychosis onset.

Multiple Linear Regression: Effects of Parental Age and PANSS on Age of First Psychotic Episode in Females With Schizophrenia.

The present results corroborate those of previous studies as well as reveal some novel findings. Considering factors that distinguish the SCH and BD diagnoses, we found that the SCH diagnosis was more often associated with lower academic performance, unemployment, and the lack of a stable long-term relationship. Both diagnoses were strongly associated with familial mental illness: SCH was strongly associated with a SCH diagnosis within the patient’s family, while BD was strongly associated with a familial BD diagnosis. Obstetric complications and schizoid-like premorbid personality characteristics were also more frequently observed in patients with SCH compared to those with BD. Logistic regression analyses suggest an interaction between family history of mental illness and obstetric trauma in predicting a SCH diagnosis relative to a BD diagnosis, and that this interaction is observed in male patients only. On the other hand, linear regression analyses indicate that younger maternal age and older paternal age at the patient’s birth were associated with an earlier onset of psychosis in the female patient group, while these associations were not observed in the male patient group.

Our results concerning academic and social function of individuals with SCH or BD are consistent with the current literature (for a complete review of such studies, see Parellada and colleagues 11 .) Thus, patients diagnosed with SCH as adults more often had shown impaired academic performance during childhood and adolescence compared to those that did not develop SCH. 22 Subjects with SCH had performed more poorly academically at age 7 (although this difference was not statistically significant), 23 and decline in cognitive function across ages 12–18 was associated with later SCH diagnosis, but not with a BD diagnosis. 24 In the present study, significantly more individuals with SCH reported not having an education beyond the secondary level, and significantly more individuals with BD reported having been enrolled in university or other post-secondary degree programs. Patients with SCH were more likely to be unemployed, while those with BD were more likely to report working at the home (e.g., homemaker).

Along with poorer premorbid academic functioning in individuals with SCH compared to those with BD, individuals with SCH are also reported to present schizoid-like personality and negative emotional characteristics during the adolescent years prior to onset of illness. In a prospective study, Jones and colleagues 22 reported that preference for solitary play, low social confidence, and increased premorbid social anxiety and schizoid-like social functioning during childhood were significantly associated with a SCH diagnosis between ages 16–43. Another prospective study interviewed healthy men at age 18; those later diagnosed with SCH were more likely to have reported having few friends, a preference to socialize in very small groups, and not having a stable long-term relationship, compared to those later diagnosed with a non-SCH psychosis. 25 Our results are in agreement with these observations: in our sample more patients with SCH described themselves as having had premorbid schizoid-like characteristics, compared to those with BD. Likewise, significantly fewer subjects with SCH reported being in a stable, long-term relationship, compared to those with BD. However, we found that having such premorbid personality characteristics was a significant positive predictor for the SCH diagnosis only in logistic regression models that included subjects with no family history of mental illness (notably, in these models, obstetric trauma did not emerge as a significant predictor). These results suggest interactions between factors of family history of mental illness, obstetric trauma, premorbid personality, and possibly gender that require further investigation.

Around half of the patients in the present study reported familial antecedents of some psychiatric disorder, and a family history of SCH and BD were by far the most commonly reported. This finding is underscores the high genetic liability of psychotic disorders and significant shared genetic risk between SCH and BD that has been consistently observed. 2 However, the present results also indicate the presence of genetic liability unique to each of these disorders: patients with SCH more often reported a family member that had SCH, while those patients with BD more often reported that a family member suffered from BD. Genetic liability unique to each of these disorders has also been previously reported in the literature. 2 , 26 Although the accuracy of our data rely on how informed the patient was with respect to their family history of mental illness (e.g., we do not have records of the actual diagnoses of the family member that suffered from mental illness), the magnitude of the difference between SCH and BD in this regard is striking ( Table 1 ). Interestingly, BD was significantly more often associated with mental illness of the patient’s mother, compared to SCH. Although this surprising finding requires replication, some studies have shown that maternal mental illness (specifically, maternal BD) might confer vulnerability to BD in the offspring due to the effects of negative maternal caregiving style on the development of the frontal lobe and executive function. 27

Our results underscore a number of gender-associated differences between SCH and BD diagnoses. Published studies have reported that males showed an earlier age of onset of SCH (3 years earlier), had poorer performance and premorbid adjustment, 28 and generally have poorer social functioning as indicated, for example, by the lack of stable long-term relationships. 29 In the present study, men were approximately one-third more likely to have a SCH diagnosis compared to women, while women were approximately 2.8 times more likely to have BD diagnosis compared to men. Men with SCH had a significantly younger age of first psychotic episode, and had significantly worse PANSS negative and PANSS total scores, compared to women. Male patients of both SCH and BD diagnostic groups were more likely than women to smoke tobacco, abuse illicit substances, and suffer from alcoholism. The present findings are important, given that male sex and family history of mental illness are factors associated with diagnostic stability in SCH over time. 30 These findings are also relevant within the clinical context, in which the specialized interventions must be differentiated by sex. One study reported that males with SCH and comorbid substance abuse were hospitalized more often, and more often subjected to mechanical restraint. 31

Our results concur with many studies that have demonstrated an association between obstetric trauma and SCH, while this association has been less consistently observed for BD. 32 – 34 “Obstetric trauma” encompasses a wide range of birth complications; in the present study patients and/or their caregivers reported hypoxia during birth, premature birth, preeclampsia, and other complications. Nevertheless, hypoxia has been identified as a specific risk factor, and its effects are suggested to be mediated by inflammation and immune mechanisms. 34 In the present study, we found that obstetric trauma (as reported retrospectively by the patient or caregiver) was specifically associated with the SCH diagnosis, and that the effect of obstetric trauma was increased in patients with familial antecedents of mental illness, strongly suggesting a gene by environment interaction, and consistent with the conclusions of previously published studies. 35 Although the literature in this area is sparse, published studies have reported possible interactions of a number of genetic variants with obstetric trauma: specific polymorphisms of the AKT1 (RAC-alpha serine/threonine protein kinase 1), BDNF (brain derived neurotrophic factor), DTN3P1 (distrobrevin binding protein 1), GRM3 (glutamate metabotrophic receptor 3), and NDE1 (NudE neurodevelopment protein 1) genes. 36 – 39 Our analyses indicate that the effects of obstetric trauma are further increased by familial psychiatric antecedents only in male patients, thereby indicating a sex by gene by environment interaction.

Finally, we found that 1 index of SCH severity, age of psychosis onset, was significantly associated in both sexes with PANSS scores. When men and women SCH patients were analyzed together, paternal age emerged as a positive predictor of age of first psychotic episode: that is, increased paternal age was associated with an older age of first psychotic episode. However, when men and women were each analyzed independently, an earlier age of onset was associated with higher PANSS negative scores, older paternal age, and younger maternal age in women only. Older paternal age has been repeatedly associated with the SCH diagnosis, while such an association has been less consistently observed for BD. 40 Few studies have examined whether this factor might differentially affect men and women, but 1 published study suggests that this effect might be slightly more important in women than in men, 41 and a meta-analysis of such studies reported that very young (less than 25 years old) paternal age was associated with SCH in men, in addition to a clear negative effect of advanced paternal age that was not sex specific. 42 Paternal age effects are suggested to be due to increased de novo mutations in the germ line, age-associated differences in sperm DNA methylation patterns, psychiatric vulnerability factors (e.g., compromised social skills) that make late fatherhood more likely, and/or certain environmental and social factors that are associated with the age of the father. 40 To our knowledge, an association between younger maternal age and SCH has not been previously reported, but such an effect could be due to physiological, environmental, or social correlates of young motherhood.

There are important limitations of the present study. Most notably, all data were retrospective, collected by interviewing the patient and his/her caregiver. Therefore, data accuracy may have been influenced by the patient’s or caregiver’s memory biases as well as by possible interviewer biases. This limitation may be particularly relevant for data on obstetric trauma, family history of mental illness, specific familial psychiatric diagnoses, and premorbid personality characteristics. However, in support of the reliability of our data set, results of the present analyses are entirely consistent with the published literature, and our novel findings are not without published precedent.

In conclusion, the present study identified a number of factors that were significantly associated with the SCH diagnosis, as compared to BD. These include generally poorer academic and social functioning, the presence of premorbid schizoid-like personality characteristics, a family history of SCH, and obstetric trauma. We found evidence that interactions between family history of mental illness, obstetric trauma, and male gender may be more associated with the SCH diagnosis as compared to BD. Our results also indicate that interactions between gender and parental age (father and/or mother) at time of the patient’s birth may be associated with an earlier age of onset of SCH psychosis. Putative interactions between genetic vulnerability, gender, and obstetric trauma should be further investigated in a neurobiological and neurodevelopmental context.

Acknowledgments

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethical approval: The database from which the present study arises is a secondary database. Dr Miguel Angel Herrera Estrella as leader investigator, authorized the use of the present database.

Lina Díaz-Castro https://orcid.org/0000-0002-9123-8641