ehaviors related to self-regulation, such as substance use disorders or antisocial behaviors, have far-reaching consequences for affected individuals, their families, communities and society at large 1,2 . Collectively, this group of correlated traits are classified as externalizing 3 . Twin studies have demonstrated that externalizing liability is highly heritable (~80%) 4,5 . To date, however, no large-scale molecular genetic studies have utilized the extensive degree of genetic overlap among externalizing traits to aid gene discovery, as most studies have focused on individual disorders 6 . For many high-cost, high-risk behaviors with an externalizing component-opioid use disorder and suicide attempts 7 being salient examples-there are limited genotyped cases available for gene discovery 8,9 .A complementary strategy to the single-disease approach is to study the shared genetic architecture across traits in multivariate analyses, which boosts statistical power by pooling data across
Background The few genetically informative studies to examine post-traumatic stress disorder (PTSD) and alcohol dependence (AD), all of which are based on a male veteran sample, suggest that the co-morbidity between PTSD and AD may be attributable in part to overlapping genetic influences, but this issue has yet to be addressed in females. Method Data were derived from an all-female twin sample (n=3768) ranging in age from 18 to 29 years. A trivariate genetic model that included trauma exposure as a separate phenotype was fitted to estimate genetic and environmental contributions to PTSD and the degree to which they overlap with those that contribute to AD, after accounting for potential confounding effects of heritable influences on trauma exposure. Results Additive genetic influences (A) accounted for 72 % of the variance in PTSD ; individual-specific environmental (E) factors accounted for the remainder. An AE model also provided the best fit for AD, for which heritability was estimated to be 71 %. The genetic correlation between PTSD and AD was 0.54. Conclusions The heritability estimate for PTSD in our sample is higher than estimates reported in earlier studies based almost exclusively on an all-male sample in which combat exposure was the precipitating traumatic event. However, our findings are consistent with the absence of evidence for shared environmental influences on PTSD and, most importantly, the substantial overlap in genetic influences on PTSD and AD reported in these investigations. Additional research addressing potential distinctions by gender in the relative contributions of genetic and environmental influences on PTSD is merited.
Context Understanding the relative contributions of genetic and environmental factors to trauma exposure, post-traumatic stress disorder (PTSD), and major depressive disorder (MDD) is critical to developing etiologic models of these conditions and their co-occurrence. Objectives To quantify heritable influences on low-risk trauma, high-risk trauma, PTSD, and MDD and to estimate the degree of overlap between genetic and environmental sources of variance in these 4 phenotypes. Design Adult twins and their siblings were ascertained from a large population-based sample of female and male twin pairs on the basis of screening items for childhood sexual abuse and physical abuse obtained in a previous assessment of this cohort. Setting Structured psychiatric telephone interviews. Participants Total sample size of 2591: 996 female and 536 male twins; 625 female and 434 male nontwin siblings. Main Outcome Measure Lifetime low- and high-risk trauma exposure, PTSD, and MDD. Results In the best-fitting genetic model, 47% of the variance in low-risk trauma exposure and 60% of the variance in high-risk trauma exposure was attributable to additive genetic factors. Heritable influences accounted for 46% of the variance in PTSD and 27% of the variance in MDD. An extremely high degree of genetic overlap was observed between high-risk trauma exposure and both PTSD (r =0.89; 95% CI, 0.78-0.99) and MDD (r =0.89; 95% CI, 0.77-0.98). Complete correlation of genetic factors contributing to PTSD and to MDD (r=1.00) was observed. Conclusions The evidence suggests that almost all the heritable influences on high-risk trauma exposure, PTSD, and MDD, can be traced to the same sources; that is, genetic risk is not disorder specific. Individuals with a positive family history of either PTSD or MDD are at elevated risk for both disorders and should be closely monitored after a traumatic experience for symptoms of PTSD and MDD.
Background All stages of development of alcohol use disorder (AUD) have not been equally studied. While initiation of drinking has been given considerable attention, other stages have not been as thoroughly investigated. It is not clear if the same factors are associated consistently across early and late transitions in AUD involvement. High risk family samples that are enriched for AUD vulnerability and transitions in AUD development offer an opportunity to examine influences across multiple stages of AUD development. Methods Data from adolescents and young adults from high risk families were used to study four transitions in AUD development –time to first drink, first drink to first problem, first drink to first diagnosis, and first problem to first diagnosis. Cox modeling was used to compare associations of parental AUD, parental separation, peer substance use, offspring ever-use of cannabis, trauma exposures and internalizing and externalizing psychopathology across transitions. Results Hazards of most transitions were elevated for those who had ever used cannabis, those who attributed substance use to their peers, those with externalizing disorders and those with parents with AUD. Many risk factors were linked to early initiation of alcohol, particularly cannabis use. Internalizing disorders were associated with later stages. Non-assaultive trauma was associated only with early initiation; assaultive trauma was not associated with any transition. . Conclusions In this large, ethnically-diverse sample of high risk youth, significant influences across transitions were fairly consistent, with externalizing disorders and cannabis ever-use elevating the likelihood of each stage, and peer and parental (and especially maternal AUD) influences linked to initiation and some later stages. Finally, in light of the increasingly permissive legal and social stances toward cannabis in the U.S., the marked elevations of all alcohol outcomes observed for cannabis use underscore the importance of studying the underpinnings of this relationship.
This report describes a 3-year follow-up study of survivors of a mass shooting incident.
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