Yale researchers find genetic clues to troubling PTSD symptom

A soldier with his head in his hands
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Symptoms of post-traumatic stress disorder (PTSD) overlap with several other psychiatric disorders, but one specific symptom — repeated disturbing memories and flashbacks about a specific event — is a defining characteristic of debilitating PTSD. 

A new genome-wide survey of 165,000 U.S. military veterans has identified eight regions of the genome associated with this re-experience of traumatic events, researchers at Yale University and University of California-San Diego report July 29 in the journal Nature Neuroscience.

The study participants were part of the Million Veteran Program launched by the Veteran’s Administration to identify genetic links to disorders affecting veterans. 

The genetic associations were found in veterans of European descent, but not in those of African ancestry, probably because there were many more European-ancestry subjects available to study, the authors say.

The gene variants found in these eight regions offer clues about the underlying biology of PTSD. Some are directly involved in stress response and others have been linked to other psychiatric disorders. One gene variant linked to PTSD is also associated with schizophrenia, another with bipolar affective disorder.

The new knowledge about genetic overlap between PTSD and schizophrenia may help to develop improved personalized treatments,” said Yale’s Joel Gelernter, the Foundations Fund Professor of Psychiatry, professor of genetics and of neuroscience, and co-senior author of the study. For example, PTSD patients with a particular genetic signature might be better candidates for treatment with antipsychotic drugs.

In some cases, the findings confirmed suspicions about role of certain biological pathways in modulating the risk of PTSD. A variant of the CRHR1 gene (Corticotropin Releasing Hormone Receptor 1) is associated with PTSD re-experiencing; this gene is also involved in steroid signaling. Another associated gene works in steroid metabolism. Both genes play key roles in stress response.

The results should also help researchers in the future study the relationship between PTSD and other potentially related psychiatric disorders, the authors said.

This study highlights the enormous potential of the Million Veteran Program as a biobank resource to identify genes important for diseases prevalent in our military veterans,” Gelernter said.

The discovery of loci with genome-wide significance is a major turning point for the field of PTSD,” said John H. Krystal, Robert L. McNeil, Jr. Professor of Neuroscience and Chair of the Yale Department of Psychiatry. “PTSD now joins the growing ranks of psychiatric disorders where scientific advances will build on risk mechanisms toward new insights into pathophysiology and treatment.”

Murray Stein of UCSD is co-senior author of the study.

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Bill Hathaway: william.hathaway@yale.edu, 203-432-1322