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

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.

Constitutive Increases in Amygdalar Corticotropin-Releasing Factor and Fatty Acid Amide Hydrolase Drive an Anxious Phenotype

“…CRF (100 nM) had no effect on eEPSP amplitude in msP neurons (Figure 5E) (101.9±6.03% of baseline, n=8 neurons from 7 rats, t (7) =0.32, N.S.). However, PF-3845 (1 μM) significantly reduced basal eEPSPs (by 15.64±3.65%, n=16 neurons from 9 rats, t (15) =4.29, + p <0.05) and this decrease persisted with the co-application of CRF (89.23±5.51% of baseline, 11/16 cells). Conversely, in Wistar neurons, CRF decreased eEPSPs (Figure 5F) (83.32 ± 3.36% of baseline, n=9 neurons from 7 rats, t (8) =4.96, + p <0.05), indicating that CRF inhibits BLA-evoked responses in the CeA.…”

Trauma and PTSD in the WHO World Mental Health Surveys

“…These questions are the subject of considerable research (Liberzon & Abelson, 2016; Sayed, Iacoviello, & Charney, 2015; Smoller, 2016). One prior consideration is the possibility that PTSD risk varies significantly by trauma type.…”

Impact of Stress on the Brain: Pathology, Treatment and Prevention

“…A more broad review then follows, covering an up-to-date overview of genetic approaches, from GWAS to epigenetics, in understanding an array of stress-related psychiatric disorders and syndromes (Smoller, 2016). John Greco and Israel Liberzon then provide a nice overview of neural circuit manifestations, based in human imaging studies, of the effects of stress, fear, and fear extinction on circuit processes and activity (Greco and Liberzon, 2016).…”