GENETICS AND TRAUMATIC STRESS

I. Why Some but Not Others?

Post-traumatic stress disorder (PTSD) is one of the most common psychiatric disorders, affecting some 8 million adults at some point in their lifetime in the United States. Despite this, it is not clear why only some people who experience a traumatic event develop PTSD. Some researchers have suggested that the disorder is only a social construct, but previous studies have hinted that genetics plays a role. A new study identifies a clear biological basis for PTSD.

However, not all research is so definitive regarding the link between traumatic stress and genetics. "Despite evidence supporting a genetic predisposition to PTSD, an insufficient amount of research has focused on identifying the precise genetic loci that account for the moderate heritability estimate. This article reviews the current state and limitations of genetic research on PTSD."

Genetic data suggests that 200,000 people possess heritability of post-traumatic stress disorder, “similar to that of depression and other forms of mental illness.” Scientists from more than 130 additional institutions, including the University of California San Diego School of Medicine, participated in the Psychiatric Genomics Consortium. Researchers discovered that PTSD has a “strong genetic component similar to other psychiatric disorders,” according to Heather Buschman, PhD.

The Genomics Consortium’s goal was to develop the tools to help “clinicians predict who is at greatest risk for PTSD and personalize their treatment approaches,” said the study’s first and corresponding author, Caroline Nievergelt, Ph.D. Dr. Nievergelt is an associate professor of psychiatry at UC San Diego School of Medicine and associate director of neuroscience in the Center of Excellence for Stress and Mental Health at the Veterans Affairs San Diego Healthcare System.

The study revealed that PTSD is “highly polygenic.” It is associated with many “genetic variants throughout the genome.” And each variant adds its part to the disorder. Senior author Karestan Koenen, an associate member of the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard and a professor of psychiatric epidemiology in the Harvard T.H. Chan School of Public Health, Karsten Koenen, offered this hopeful assessment, “Based on these findings, we can say with certainty that there is just as much of a genetic component to PTSD risk as major depression and other mental illnesses.”

II. PTSD is polygenic

“(T)he genetic component of many of the most important health conditions of our time — cancer, heart disease, diabetes — are due to the effects of multiple genes. Hence, polygenic, or many genes. This knowledge has been a fascinating area of study, as scientists have begun to study these conditions and realized that the ways that we have of predicting risks for polygenic traits have tremendous potential for improving human health.”

Of the 200,000-person study published in 2017, a 12-country network comprised of 200 scientists took D.N.A. samples from over 60 groups of people diagnosed with P.T.S.D., which included the U.K. Biobank. Twenty-three thousand people of European descent and almost 4,000 of African descent participated in the genome research. It is “international” in scope “and is highly diverse,” Caroline Nievergelt said. “There’s greater representation here than in most studies to date.”

Scientists compared “genetic correlations between P.T.S.D. and 235 other disorders, behaviors and physical traits.” There appears to be a notable connection between P.T.S.D. and twenty-one disorders, including depression, schizophrenia, neuroticism, insomnia, asthma, and coronary artery disease. What this means is yet to be determined, and more study is required.

III. Predictive potential

Scientists are using the data from the UK Biobank to develop a polygenic score for understanding who might be susceptible to PTSD diagnosis through computations of genetic variations. “Those with the highest scores had 0.4-fold higher odds of developing than those with the lowest. . . — a key PTSD symptom.” More time is required to study the data to improve PTSD accuracy and, hence, prediction. 

Koenen said, “If you look across psychiatric genetics, it's taken even larger sample sizes than we have here to make robust genetic discoveries.” But it’s a good start from all accounts. 

Co-senior author Joel Gelernter, the Foundations Fund Professor of Psychiatry and professor of genetics and neurobiology at Yale, believes this new study will modify medications already prescribed to sufferers.

In a Jan. 28, 2021 study in the journal Nature Genetics, 250,000 veterans, 36,000 of which had been diagnosed with P.T.S.D., scientists “searched for variants that have been linked to three kinds of clinical symptoms that are experienced, to varying degrees, by those diagnosed with the disorder.” The symptom groups, or ‘subdomains,’ included the re-living of a joint traumatic event. These re-experiences included “hyperarousal or acute anger and irritability, and the avoidance of people or subjects that might be related to past trauma.


“We found a remarkably high degree of genetic relatedness between these three symptom subdomains. But we also wouldn’t expect them to be genetically identical, and they are not,” Gelernter said. “We found biological support for different clinical presentations of PTSD.”

In terms of medications, some of which are being used for other diseases may be “repurposed” for traumatic stress.