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.

The DSM-5 includes a novel approach to the diagnosis of personality disorders (PDs) in Section III, in order to stimulate further research with the possibility that this proposal will be included more formally in future DSM iterations. The current study provides the first test of this proposal in a clinical sample by simultaneously examining its two primary components: a system for rating personality impairment and a newly developed dimensional model of pathological personality traits. Participants were community adults currently receiving outpatient mental health treatment who completed a semi-structured interview for DSM-IV PDs and were then rated in terms of personality impairment and pathological traits. Data on the pathological traits were also collected via self-reports using the Personality Inventory for DSM-5 (PID-5). Both sets of trait scores were compared to self-report measures of general personality traits, internalizing symptoms, and externalizing behaviors. Inter-rater reliabilities for the clinicians’ ratings of impairment and the pathological traits were fair. The impairment ratings manifested substantial correlations with symptoms of depression and anxiety, DSM-5 PDs, and DSM-5 pathological traits. The clinician and self-reported personality trait scores demonstrated good convergence with one another, both accounted for substantial variance in DSM-IV PD constructs, and both manifested expected relations with the external criteria. The traits but not the impairment ratings demonstrated incremental validity in the prediction of the DSM-IV PDs. Overall, the current results support the general validity of several of the components of this new PD diagnostic system and point to areas that may require further modification.

Objective Increased systemic inflammation is associated with stress-related psychopathology. Specifically, levels of the pro-inflammatory marker C-reactive protein (CRP) are increased in individuals with posttraumatic stress disorder (PTSD). Furthermore, single nucleotide polymorphisms (SNPs) in the CRP gene are associated with CRP levels, risk for cardiovascular disease and obesity. We examined whether polymorphisms within the CRP gene and increased CRP levels are associated with PTSD symptoms and fear physiology in a highly traumatized civilian population. Method Cross-sectional data were collected from subjects recruited from an inner-city public hospital that serves a primarily African American, low socioeconomic population. Participants were interviewed to determine PTSD symptom severity, and a fear-potentiated startle (FPS) paradigm was administered to assess fear-related phenotypes of PTSD. Results One SNP within the CRP gene, rs1130864, was significantly associated with increased PTSD symptoms (N=2692; p=0.004), including ‘being overly alert’ as the most significant individual symptom (N=2698; p =1.5×10−5). Additionally CRP genotype was also associated with the odds of PTSD diagnosis (N=2692; p=0.004). This SNP was also associated with increased CRP levels (N=137; p=0.007), and high CRP levels (>3mg/L) were positively associated with PTSD symptoms (N=187; p=0.032) and FPS to a safety signal (N=135; p<0.005). Conclusions Together, these data indicate that genetic variability in the CRP gene is associated with increased CRP levels and PTSD symptoms, including hyperarousal symptoms. Increased CRP levels were also associated with exacerbated fear-related psychophysiology and PTSD symptoms and diagnosis. These findings offer a potential mechanism by which an increased pro-inflammatory state may lead to heightened PTSD symptoms.

Background Civilian posttraumatic stress disorder (PTSD) and combat PTSD are major public health concerns. Although a number of psychosocial risk factors have been identified related to PTSD risk, there are no accepted, robust biological predictors that identify who will develop PTSD or who will respond to early intervention following trauma. We wished to examine whether genetic risk for PTSD can be mitigated with an early intervention. Method 65 emergency department patients recruited in 2009–2010 at Grady Memorial Hospital in Atlanta, Georgia, who met criterion A of DSM-IV PTSD received either 3 sessions of an exposure intervention, beginning in the emergency department shortly after trauma exposure or assessment only. PTSD symptoms were assessed 4 and 12 weeks after trauma exposure. A composite additive risk score was derived from polymorphisms in 10 previously identified genes associated with stress-response (ADCYAP1R1, COMT, CRHR1, DBH, DRD2, FAAH, FKBP5, NPY, NTRK2, and PCLO), and gene x treatment effects were examined. The intervention included 3 sessions of imaginal exposure to the trauma memory and additional exposure homework. The primary outcome measure was the PTSD Symptom Scale-Interview Version or DSM-IV–based PTSD diagnosis in patients related to genotype and treatment group. Results A gene x intervention x time effect was detected for individual polymorphisms, in particular the PACAP receptor, ADCYAP1R1, as well as with a combined genotype risk score created from independent SNP markers. Subjects who did not receive treatment had higher symptoms than those who received intervention. Furthermore, subjects with the “risk” genotypes who did not receive intervention had higher PTSD symptoms compared to those with the “low-risk” or “resilience” genotypes or those who received intervention. Additionally, PTSD symptoms correlated with level of genetic risk at week 12 (P < .005) in the assessment-only group, but with no relationship in the intervention group, even after controlling for age, sex, race, education, income, and childhood trauma. Using logistic regression, the number of risk alleles was significantly associated with likelihood of PTSD diagnosis at week 12 (P < .05). Conclusions This pilot prospective study suggests that combined genetic variants may serve to predict those most at risk for developing PTSD following trauma. A psychotherapeutic intervention initiated in the emergency department within hours of the trauma may mitigate this risk. The role of genetic predictors of risk and resilience should be further evaluated in larger, prospective intervention and prevention trials. Trial Registration ClinicalTrials.gov identifier: NCT00895518