Genetic approaches to understanding post-traumatic stress disorder

Abstract

Post-traumatic stress disorder (PTSD) is increasingly recognized as both a disorder of enormous mental health and societal burden, but also as an anxiety disorder that may be particularly understandable from a scientific perspective. Specifically, PTSD can be conceptualized as a disorder of fear and stress dysregulation, and the neural circuitry underlying these pathways in both animals and humans are becoming increasingly well understood. Furthermore, PTSD is the only disorder in psychiatry in which the initiating factor, the trauma exposure, can be identified. Thus, the pathophysiology of the fear and stress response underlying PTSD can be examined and potentially interrupted. Twin studies have shown that the development of PTSD following a trauma is heritable, and that genetic risk factors may account for up to 30–40% of this heritability. A current goal is to understand the gene pathways that are associated with PTSD, and how those genes act on the fear/stress circuitry to mediate risk vs. resilience for PTSD. This review will examine gene pathways that have recently been analysed, primarily through candidate gene studies (including neuroimaging studies of candidate genes), in addition to genome-wide associations and the epigenetic regulation of PTSD. Future and on-going studies are utilizing larger and collaborative cohorts to identify novel gene candidates through genome-wide association and other powerful genomic approaches. Identification of PTSD biological pathways strengthens the hope of progress in the mechanistic understanding of a model psychiatric disorder and allows for the development of targeted treatments and interventions.

Prevention of Trauma and Stressor-Related Disorders: A Review

“…Candidate gene studies, in which genes are selected for study based on biological pathways thought to have a role in PTSD, have identified a number of genes possibly associated with risk of PTSD. These include genes involved in the hypothalamicpituitary-adrenal (HPA) axis, the noradrenergic, serotonergic and dopaminergic systems, memory consolidation, and other biological systems (Almli et al, 2014;Logue et al, 2015). However, some of these candidate gene studies have failed to replicate.…”

Genomic predictors of combat stress vulnerability and resilience in U.S. Marines: A genome-wide association study across multiple ancestries implicates PRTFDC1 as a potential PTSD gene

“…Until recently, the genetic contribution to PTSD has been investigated largely via candidate gene association studies (reviewed in Almli et al, 2014;Amstadter et al, 2009;Norrholm and Ressler, 2009). Most research has focused on: (1) the hypothalamic-pituitary-adrenal (HPA) axis, (2) the ascending brainstem locus coeruleus noradrenergic system, and (3) the limbic amygdalar frontal pathway mediating fear processing.…”

The Effects of a <b><i>BDNF</i></b> Val66Met Polymorphism on Posttraumatic Stress Disorder: A Meta-Analysis

“…Candidate studies of PTSD have identified > 50 genes that exert significant effects (for reviews, see [22, 23]), with some finding a significant effect of the Val66Met BDNF polymorphism on PTSD [24]. This polymorphism is functional, as the Met allele is associated with reduced BDNF gene expression [25], impeding the extinction of conditioned fear [26].…”