The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders.

Neuropsychopharmacology
Authors
Keywords
Abstract

Research into the causes of psychopathology has largely focused on two broad etiologic factors: genetic vulnerability and environmental stressors. An important role for familial/heritable factors in the etiology of a broad range of psychiatric disorders was established well before the modern era of genomic research. This review focuses on the genetic basis of three disorder categories-posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and the anxiety disorders-for which environmental stressors and stress responses are understood to be central to pathogenesis. Each of these disorders aggregates in families and is moderately heritable. More recently, molecular genetic approaches, including genome-wide studies of genetic variation, have been applied to identify specific risk variants. In this review, I summarize evidence for genetic contributions to PTSD, MDD, and the anxiety disorders including genetic epidemiology, the role of common genetic variation, the role of rare and structural variation, and the role of gene-environment interaction. Available data suggest that stress-related disorders are highly complex and polygenic and, despite substantial progress in other areas of psychiatric genetics, few risk loci have been identified for these disorders. Progress in this area will likely require analysis of much larger sample sizes than have been reported to date. The phenotypic complexity and genetic overlap among these disorders present further challenges. The review concludes with a discussion of prospects for clinical translation of genetic findings and future directions for research.

Year of Publication
2016
Journal
Neuropsychopharmacology
Volume
41
Issue
1
Pages
297-319
Date Published
2016 Jan
ISSN
1740-634X
URL
DOI
10.1038/npp.2015.266
PubMed ID
26321314
PubMed Central ID
PMC4677147
Links
Grant list
K24 MH094614 / MH / NIMH NIH HHS / United States
R01 MH101486 / MH / NIMH NIH HHS / United States
K24MH094614 / MH / NIMH NIH HHS / United States
R01MH101486 / MH / NIMH NIH HHS / United States