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.

Objective While it is now recognized that psychotic experiences (PEs) are associated with an increased risk of later mental disorders, we lack a detailed understanding of the reciprocal time-lagged relationships between first onsets of PEs and mental disorders. Methods The WHO World Mental Health (WMH) surveys assessed lifetime prevalence and age-of-onset of PEs and 21 common DSM-IV mental disorders among 31,261 adult respondents from 18 countries. Results Temporally primary PEs were significantly associated with subsequent first onset of 8 of the 21 mental disorders (major depressive disorder, bipolar disorder, generalized anxiety disorder, social phobia, post-traumatic stress disorder, adult separation anxiety disorder, bulimia nervosa, alcohol abuse), with ORs (95%CI) ranging from 1.3 (1.2–1.5; major depressive disorder) to 2.0 (1.5–2.6; bipolar disorder). In contrast, 18 of 21 primary mental disorders were significantly associated with subsequent first onset of PEs, with ORs (95% CI) ranging from 1.5 (1.0–2.1; childhood separation anxiety disorder) to 2.8 (1.0–7.8; anorexia nervosa). Conclusions While temporally primary PEs are associated with an elevated risk of several subsequent mental disorders, we found that most mental disorder are associated with an elevated risk of subsequent PEs. Further investigation of the underlying factors accounting for these time-order relationships might shed light on the etiology of PEs.

International Prospective Register of Systematic Reviews (PROSPERO) identifier: CRD42016032973.

Post-traumatic stress disorder (PTSD) should be one of the most preventable mental disorders, since many people exposed to traumatic experiences (TEs) could be targeted in first response settings in the immediate aftermath of exposure for preventive intervention. However, these interventions are costly and the proportion of TE-exposed people who develop PTSD is small. To be cost-effective, risk prediction rules are needed to target high-risk people in the immediate aftermath of a TE. Although a number of studies have been carried out to examine prospective predictors of PTSD among people recently exposed to TEs, most were either small or focused on a narrow sample, making it unclear how well PTSD can be predicted in the total population of people exposed to TEs. The current report investigates this issue in a large sample based on the World Health Organization (WHO)'s World Mental Health Surveys. Retrospective reports were obtained on the predictors of PTSD associated with 47,466 TE exposures in representative community surveys carried out in 24 countries. Machine learning methods (random forests, penalized regression, super learner) were used to develop a model predicting PTSD from information about TE type, sociodemographics, and prior histories of cumulative TE exposure and DSM-IV disorders. DSM-IV PTSD prevalence was 4.0% across the 47,466 TE exposures. 95.6% of these PTSD cases were associated with the 10.0% of exposures (i.e., 4,747) classified by machine learning algorithm as having highest predicted PTSD risk. The 47,466 exposures were divided into 20 ventiles (20 groups of equal size) ranked by predicted PTSD risk. PTSD occurred after 56.3% of the TEs in the highest-risk ventile, 20.0% of the TEs in the second highest ventile, and 0.0-1.3% of the TEs in the 18 remaining ventiles. These patterns of differential risk were quite stable across demographic-geographic sub-samples. These results demonstrate that a sensitive risk algorithm can be created using data collected in the immediate aftermath of TE exposure to target people at highest risk of PTSD. However, validation of the algorithm is needed in prospective samples, and additional work is warranted to refine the algorithm both in terms of determining a minimum required predictor set and developing a practical administration and scoring protocol that can be used in routine clinical practice.

The current treatment gap in mental health care in Latin America and the Caribbean remains wide. Further, current data likely greatly underestimate the number of untreated individuals. The epidemiological transition and changes in the population structure will further widen the treatment gap in Latin America and the Caribbean unless mental health policies are formulated or updated and programs and services are expanded.