The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations.

National Health and Medical Research Council.

Findings suggest that the long-term impact of a prominent trauma in childhood should be assessed in the context of other lifetime trauma in order to provide a more accurate account of PTSD prevalence rates.

BackgroundThe Australian Defence Force (ADF) Mental Health Prevalence and Wellbeing Study (MHPWS) is the first study of mental disorder prevalence in an entire military population.ObjectiveThe MHPWS aims to establish mental disorder prevalence, refine current ADF mental health screening methods, and identify specific occupational factors that influence mental health. This paper describes the design, sampling strategies, and methodology used in this study.MethodAt Phase 1, approximately half of all regular Navy, Army, and Air Force personnel (n=24,481) completed self-report questionnaires. At Phase 2, a stratified sub-sample (n=1,798) completed a structured diagnostic interview to detect mental disorder. Based on data from non-responders, data were weighted to represent the entire ADF population (n=50,049).ResultsOne in five ADF members met criteria for a 12-month mental disorder (22%). The most common disorder category was anxiety disorders (14.8%), followed by affective (9.5%) and alcohol disorders (5.2%). At risk ADF sub-groups were Army personnel, and those in the lower ranks. Deployment status did not have an impact on mental disorder rates.ConclusionThis study has important implications for mental health service delivery for Australian and international military personnel as well as contemporary veterans.

Despite the substantial body of neurobiological research, no specific drug target has been developed to treat PTSD and there are substantial limitations with the available interventions. We propose that advances are likely to depend on the development of better classification of the heterogeneity of PTSD using a staging approach of disease. A primary rationale for staging is to highlight the probability that distinct therapeutic approaches need to be utilised according to the degree of biological progression of the disorder. Prospective studies, particularly of military populations, provide substantial evidence about the emerging biological abnormalities that precede the full-blown disorder. These need to be targeted with tailored interventions to prevent disease progression. Equally, the neurobiology of chronic unremitting PTSD needs to be differentiated from the acute disorder which emerges across a spectrum of severity, and this range of presentations correspondingly needs to be addressed with differing therapeutic strategies. The staging approach also needs to take account of the range of somatic pathological outcomes that are being identified as a consequence of traumatic stress exposure. PTSD should be conceptualised as a systemic disorder underpinned a range of biological dysregulation, including metabolic and altered immune function, reflected in the increased rates of cardiovascular and autoimmune disease. The effectiveness of novel treatments needs to be judged across their effectiveness in addressing the spectrum of trauma-related pathology.