Genetic Vulnerability to PTSD Identified

Armen K. Goenjian, M.D., L.D.F.A.P.A., F.A.C.G.S. Research Professor of Psychiatry Department of Psychiatry and Biobehavioral Sciences David Geffen School of Medicine at UCLAMedicalResearch.com Interview with:
Armen K. Goenjian, M.D., L.D.F.A.P.A., F.A.C.G.S.
Research Professor of Psychiatry
Department of Psychiatry and Biobehavioral Sciences
David Geffen School of Medicine at UCLA

Medical Research: What is the background for this study?

Response: Post-traumatic stress disorder (PTSD) is a psychiatric disorder that develops after exposure to a traumatic event such as rape, war, natural disaster, and accident. Symptoms include recurrent intrusive traumatic memories, flashbacks, nightmares, hyper-vigilance, jumpiness, and anxiety.

Dopaminergic and serotonergic systems have been implicated in PTSD. Catechol-O-methyltransferase (COMT) is an enzyme that degrades dopamine, an important brain neuro-hormone that regulates human behavior, thoughts and emotions.  Tryptophan hydroxylase is the rate limiting step in the synthesis of serotonin, another important neuro-hormone that regulates arousal, sleep, anxiety, and mood. This study evaluated the association of four COMT gene loci, and the joint effect of COMT and tryptophan hydroxylase 2 (TPH-2) genes on PTSD symptoms.

Medical Research: What are the main findings?

Response: Subjects included 200 Caucasian Armenian adults exposed to the 1988 Spitak earthquake from 12 multigenerational (3 to 5) families.

Heritability of vulnerability to PTSD symptoms was 60% based on DSM-5 criteria (the new diagnostic criteria of the American Psychiatric Association). This was higher than formerly reported (41%) using the older (DSM-IV) criteria.   There was a significant association between COMT SNP allele (genetic variant) 4633C and DSM-5 based total PTSD. Also, there was a significant association between TPH-2 allele rs11178997T and PTSD symptoms.  The two genetic variants jointly explained 7% of the variance in PTSD symptoms.

Medical Research: What should clinicians and patients take away from your report?

Clinicians should bear in mind that patients may respond differentially to the same traumatic event and similar treatments not only on the basis of environmental variables (e.g. severity of exposure to the trauma, family conflicts) but also on the basis of their genetic vulnerability.

The two variants of the 2 genes (COMT and TPH-2) may be causally related and/or are in linkage disequilibrium with gene(s) that are causally related to PTSD symptoms. Carriers of these genetic variants may be at risk for PTSD.

DSM-5 based assessments of PTSD symptoms may increase the prospects of finding genes associated with PTSD.

Medical Research: What recommendations do you have for future research as a result of this study?

Response: It is important to replicate these findings in this and other racial/ethnic group.  Also, it will be helpful to study these genes in animals. PTSD is a polygenic disorder. The ultimate goal is to find all (or most) of the genes involved with PTSD and target therapy accordingly instead of using a gun-shot approach.

Citation:

Association of COMT and TPH-2 Genes with DSM-5 based PTSD Symptoms

Armen K. Goenjian Ernest P. Noble Alan M. Steinberg David P. Walling, Sofia T. Stepanyan Sugandha Dandekar Julia N. Bailey
Journal of Affective Disorders
Volume 172, 1 February 2015, Pages 472–478