Differences in genetic correlations between posttraumatic stress disorder and alcohol-related problems phenotypes compared to alcohol consumption-related phenotypes.

BACKGROUND: Posttraumatic Stress Disorder (PTSD) tends to co-occur with greater alcohol consumption as well as alcohol use disorder (AUD). However, it is unknown whether the same etiologic factors that underlie PTSD-alcohol-related problems comorbidity also contribute to PTSD- alcohol consumption. METHODS: We used summary statistics from large-scale genome-wide association studies (GWAS) of European-ancestry (EA) and African-ancestry (AA) participants to estimate genetic correlations between PTSD and a range of alcohol consumption-related and alcohol-related problems phenotypes. RESULTS: In EAs, there were positive genetic correlations between PTSD phenotypes and alcohol-related problems phenotypes (e.g. Alcohol Use Disorders Identification Test (AUDIT) problem score) (rGs: 0.132-0.533, all FDR adjusted p < 0.05). However, the genetic correlations between PTSD phenotypes and alcohol consumption -related phenotypes (e.g. drinks per week) were negatively associated or non-significant (rGs: -0.417 to -0.042, FDR adjusted p: <0.05-NS). For AAs, the direction of correlations was sometimes consistent and sometimes inconsistent with that in EAs, and the ranges were larger (rGs for alcohol-related problems: -0.275 to 0.266, FDR adjusted p: NS, alcohol consumption-related: 0.145-0.699, FDR adjusted p: NS). CONCLUSIONS: These findings illustrate that the genetic associations between consumption and problem alcohol phenotypes and PTSD differ in both strength and direction. Thus, the genetic factors that may lead someone to develop PTSD and high levels of alcohol consumption are not the same as those that lead someone to develop PTSD and alcohol-related problems. Discussion around needing improved methods to better estimate heritabilities and genetic correlations in diverse and admixed ancestry samples is provided.

The effect of a reduction in irrational beliefs on Posttraumatic Stress Disorder (PTSD), depression, and anxiety symptoms in a group treatment for post-9/11 Veterans.

Previous research has indicated that a Rational Emotive Behavior Therapy (REBT)-Informed Group focused on changing irrational beliefs to address comorbid depression and anxiety (as well as anger and guilt) in a combat Veteran population diagnosed with Posttraumatic Stress Disorder (PTSD) demonstrated significant reductions in depression and PTSD symptoms at posttreatment. However, mechanisms of change associated with improvement have not been evaluated. REBT theory suggests that a decline in irrational beliefs predicts a decrease in PTSD, depression, and anxiety symptoms. This study aimed to test this tenet of REBT theory in a naturalistic treatment setting. Participants (N = 86) were post-9/11 combat Veterans, engaged in the REBT-Informed Group between October 2016 and February 2020. Results of hierarchical multiple regression analyses indicated that a reduction in irrational beliefs predicted notable decreases in PTSD, depression, and anxiety symptoms controlling for several covariates. This study extends previous research demonstrating the success of the REBT-Informed Group with combat Veterans and gives support to REBT theory regarding the effect of a decline in irrational beliefs. Future directions include replication of findings with Veterans who experienced military sexual trauma (MST), pre-9/11 Veterans, those at other military or Veterans Affairs (VA) medical centers, and civilians to determine generalizability.

Modeling the association between and predictors of two constructs of resilience.

PURPOSE: Resilience serves as a protective factor against adverse outcomes following exposure to traumatic events. The extant literature focuses on psychiatric resilience in the context of internalizing symptoms, though resilience is also important in relation to externalizing symptoms. Research is needed to clarify the predictors of resilience across contexts. The aims of the current study are twofold: 1. Determine the association between psychiatric resilience (PR) and alcohol resistance (AR) and 2. Test for differential prediction of each form of resilience by exogenous predictors. METHODS: The sample (n = 7585) was drawn from the Virginia Adult Twin Studies of Psychiatric and Substance Use Disorders (VATSPSUD). Participants completed measures of internalizing symptoms, exposure to stressful life events, DSM alcohol abuse and dependence symptoms, maximum alcohol consumption, personality variables, and social support. All cross-sectional, structural equation modeling (SEM) analyses were conducted using Mplus software version 8.2. RESULTS: A single common factor model provided adequate fits for both PR and AR. In the full measurement model the correlation between the two resilience factors was estimated (r = 0.28, SE = 0.018, p < 0.001). Neuroticism and mastery predicted AR and PR, but differentially, with a stronger effect size for PR (neuroticism: B = 0.35, p < 0.001; mastery: B = - 0.36, p < 0.001). The positive social support factor did not predict either resilience variable, while interpersonal conflict was associated with both (AR = 0.09, p < 0.001; PR = 0.07, p < 0.001). CONCLUSIONS: Findings extend the current literature on resilience in two ways. First, rigorous measurement model based definitions of two resilience variables are specified. Second, external validation of the AR and PR constructs is carried out using latent variable modeling techniques. The modest correlation suggests resilience may not be well-characterized by a single general attribute. Findings provide further evidence for predictors of resilience by way of displaying differential patterns of prediction effect sizes of PR and AR.

Psychiatric Resilience and Alcohol Resistance: A Twin Study of Genetic Correlation and Sex Differences.

Variability in psychiatric response following stressful/traumatic life events is frequently observed. There is also variability in propensity for alcohol use disorder (AUD) such that some can consume substantial amounts and not develop AUD symptoms whereas others develop an AUD. Our group has applied discrepancy-based approaches to capture psychiatric resilience (PR) and alcohol resistance (AR), both moderately heritable. This study sought to (1) examine the genetic and environmental correlation of these constructs and (2) model qualitative and quantitative sex effects. Data came from a large twin sample (N = 4501 twin pairs) with self-report measures and interviews assessing distress symptoms, stressful life events, alcohol use, and AUD. Correlated liability model results suggested a moderate degree of genetic correlation between PR and AR (0.54) due to the same genetic factors in males and females. Findings highlight the shared genetic predisposition of these resilience/resistance constructs while emphasizing the impact of unique environmental experiences.

Potential causal effect of posttraumatic stress disorder on alcohol use disorder and alcohol consumption in individuals of European descent: A Mendelian Randomization Study.

BACKGROUND: Posttraumatic stress disorder (PTSD) often co-occurs with alcohol consumption (AC) and alcohol use disorder (AUD). However, it is unknown whether the same etiologic influences that underlie PTSD co-occurring with AUD are those that underlie PTSD and AC individually. METHODS: This study used large-scale genome-wide association study (GWAS) data to test whether PTSD and drinks per week [DPW]/AUD are causally related to one another, and, if so, whether PTSD precedes DPW/AUD and/or vice versa. We used Mendelian Randomization methods to analyze European ancestry GWAS summary statistics from the Psychiatric Genomics Consortium (PGC; PTSD), GWAS & Sequencing Consortium of Alcohol and Nicotine Use (GSCAN; DPW), and the Million Veteran Program (MVP; AUD). RESULTS: PTSD exerted a potentially causal effect on AUD (ß = 0.039, SE = 0.014, p = 0.005), but not on DPW (ß = 0.002, SE = 0.003, p = 0.414). Additionally, neither DPW (ß = 0.019, SE = 0.041, p = 0.637) nor AUD (ß = 8.87 × 10-4 , SE = 0.001, p = 0.441) exerted a causal effect on PTSD. CONCLUSIONS: These findings are consistent with the self-medication model, in which individuals misuse alcohol to cope with aversive trauma-related symptoms. These findings extend latent analysis and molecular findings of shared and correlated risk between PTSD and alcohol phenotypes. Given the health behaviors associated with these phenotypes, these findings are important in that they suggest groups to prioritize for prevention efforts. Further, they provide a rationale for future preclinical and clinical studies examining the biological mechanisms by which PTSD may impact AUD.

Epigenome-Wide Study of Posttraumatic Stress Disorder Symptom Severity in a Treatment-Seeking Adolescent Sample.

Emerging research has demonstrated that psychosocial trauma exposure may elicit epigenetic changes, with downstream effects on the transcriptional regulation of genes. Epigenome-wide association studies (EWAS) offer an agnostic approach to examine DNA methylation (DNAm) associations and are a valuable tool to aid in the identification of biological pathways involved in posttraumatic stress disorder (PTSD). This study represents the first EWAS of PTSD in an adolescent sample, an important group given the significance of this developmental period regarding both DNAm changes and PTSD risk. The sample (n = 39, M age = 15.41 years, SD = 1.27, 84.6% female) comprised adolescents who experienced interpersonal trauma and were enrolled in a treatment study. Participants were assessed using the UCLA PTSD Reaction Index for DSM-IV-Adolescent Version and provided a blood sample at baseline. Genomic DNA was isolated from whole blood and assayed using the Illumina Infinium MethylationEPIC BeadChip. The primary analysis estimated the associations among individual CpG sites and PTSD symptom scores. Of the 793,575 screened probes tested, two were significant at a false discovery rate (FDR) < 10%. Hypomethylation of both sites was associated with increased PTSD symptom scores. Analysis of differentially methylated regions (DMR) identified a DMR associated with PTSD symptom scores at an FDR < 10%. Results from follow-up models are also discussed. Findings from this preliminary investigation suggest the importance of further research conducted in adolescent samples. The analytic pipeline and results are documented for use in future meta-analytic work as more such samples become available.

Longitudinal Examination of the Impact of Resilience and Stressful Life Events on Alcohol Use Disorder Outcomes.

Stressful life events (SLEs) are a risk factor for alcohol use problems, and there is a need for identification of factors that may offset this risk. Resilience is uniquely, inversely associated with alcohol use, but there remains a dearth of research examining the buffering effect of resilience toward alcohol use problems in the context of SLEs. Objectives: This study used prospective data from an epidemiological twin sample (N = 7441) to test whether resilience at Time 1 would act as a buffer for new onset SLEs (e.g. assault, marital problems) against risk for alcohol dependence (AD) symptoms at Time 2. Results: The final model, adjusted for familial relatedness and controlling for demographic covariates and Time 1 (lifetime) AD symptoms, identified significant main effects of resilience and SLEs; those with greater resilience at Time 1 reported fewer symptoms (ß=-.087, p<.001) and those with greater new-onset SLEs reported greater symptoms (ß=.116, p<.001) at Time 2. However, there was no significant interaction (ß=-.008, p>.05). Conclusions: Although findings further support the association of resilience and SLEs with AD, results do not support the conceptualization of resilience as a buffer against the impact of future life stressors on alcohol use outcomes. This suggests other factors may be more relevant for understanding protective factors for alcohol use problems or the relation between resilience and SLEs on alcohol use outcomes.

Intraindividual association of PTSD symptoms with binge drinking among trauma-exposed students.

People, particularly undergraduate students, who report elevated symptoms of posttraumatic stress disorder (PTSD) are at elevated risk of binge drinking. The present study used ecological momentary assessment to (a) evaluate whether PTSD severity, specifically, or psychological distress, generally, are associated with binge drinking and (b) examine the self-medication and susceptibility models of the comorbidity of PTSD with binge drinking while accounting for shared liability (i.e., the between-person association of PTSD symptom severity with binge drinking). Within a larger study of undergraduate student mental health, for 14 days, students who reported a potentially traumatic experience (N = 276) reported nightly on use of alcohol and psychoactive substances and thrice daily on current affect, internalizing symptoms, and PTSD symptoms. Daily binge drinking, per the NIAAA definition, was analyzed using multivariate mixed effects, multilevel logistic regression. Results support the self-medication model; participants were more likely to binge drink on days marked by elevated PTSD symptoms, OR = 2.82, p < .01. Binge drinking was also more likely on weekends, OR = 4.21, p < .0001, and days marked by elevated daily positive affect, OR = 1.60, p < .001. Binge drinking was not associated with concurrent depressive or general anxiety symptoms (p > .30). PTSD symptoms were not associated with use of cannabis or other substances (p > .06). Regarding the susceptibility model, following a binge drinking episode, participants reported elevated depressive symptoms, B = 0.34, p = .04, but no change in affect, PTSD symptoms, or general anxiety symptoms (p > .16). Results suggest that, beyond understanding who is at risk for binge drinking, fluctuations in PTSD severity clarify when students engage in binge drinking. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

A behavioral genetic investigation of conceptualizations of resilience in a female twin sample.

BACKGROUND: Great variability exists in response to stressful or traumatic events, leading to an interest in the construct of resilience as a trait and an outcome. The etiologic sources of variability across differing conceptualizations of resilience are poorly understood. METHODS: Using behavioral genetic methods in a sample of 2,056 female twins, the present study sought to (a) examine the etiologic sources of a trait-based self-report measure of perceived resilience (PR), (b) determine the genetic and environmental overlap with an outcome-based measure of resilience, as defined by the absence of psychiatric symptoms after stressful life events, previously used by our research team (discrepancy-based psychiatric resilience [DBPR]), and (c) determine the etiologic overlap of these two resilience measures with major depressive disorder (MDD). RESULTS: PR was modestly (11%) heritable. A moderate degree of genetic overlap (39%) and a nominal amount of environmental overlap (3%) were found between the two alternative measures of resilience. Genetic factors that influence PR accounted for 3% of MDD heritability, whereas 31% of MDD heritability was due to DBPR genetic factors. CONCLUSIONS: Findings of a higher genetic correlation between the outcome-based resilience measure and MDD compared to the trait-based measure and MDD suggest gene-finding efforts may benefit from considering the multifaceted nature of resilience and that resilience is best understood as both a phenotypically and genetically heterogeneous construct.

Meta-Analysis of Associations Between Hypothalamic-Pituitary-Adrenal Axis Genes and Risk of Posttraumatic Stress Disorder.

The hypothalamic-pituitary-adrenal (HPA) axis has been of interest in attempts to identify genetic vulnerability for posttraumatic stress disorder (PTSD). Although numerous HPA-axis genes have been implicated in candidate gene studies, the findings are mixed and interpretation is limited by study design and methodological inconsistencies. To address these inconsistencies in the PTSD candidate gene literature, we conducted meta-analyses of HPA-related genes from both a traditional single nucleotide polymorphism (SNP)-level analysis and a gene-level analysis, using novel methods aggregating markers in the same gene. Database searches (PubMed and PsycINFO) identified 24 unique articles examining six HPA-axis genes in PTSD; analyses were conducted on four genes (ADCYAP1R1, CRHR1, FKBP5, NR3C1) that met study eligibility criteria (original research, human subjects, main effect association study of selected genes, PTSD as an outcome, trauma-exposed control group) and had sufficient data and number of studies for use in meta-analysis, within 20 unique articles. Findings from SNP-level analyses indicated that two variants (rs9296158 in FKBP5 and rs258747 in NR3C1) were nominally associated with PTSD, ps = .001 and .001, respectively, following multiple testing correction. At the gene level, significant relations between PTSD and both NR3C1 and FKBP5 were detected and robust to sensitivity analyses. Although study limitations exist (e.g., varied outcomes, inability to test moderators), taken together, these results provide support for FKBP5 and NR3C1 in risk for PTSD. Overall, this work highlights the utility of meta-analyses in resolving discrepancies in the literature and the value of adopting gene-level approaches to investigate the etiology of PTSD.

The impact of resilience and subsequent stressful life events on MDD and GAD.

BACKGROUND: There remains a dearth of research examining the "buffering" effect of resilience, wherein resilience at one point in time would be expected to protect an individual against development of psychopathology following future adverse life events. METHODS: Using longitudinal data from an epidemiological twin sample (N = 7463), this study tested whether resilience would act as a buffer for stressful life events (SLEs) against risk for major depressive disorder (MDD) and generalized anxiety disorder (GAD). Resilience, demographics, and psychopathology were measured at Time 1 and recent SLEs and current MDD and GAD were measured at Time 2. RESULTS: Final models, controlling for demographic covariates and Time 1 diagnosis, examined the impact of Time 1 resilience, recent SLEs, their interaction, and a three-way interaction adding sex on MDD and GAD. CONCLUSIONS: The pattern of findings was the same for MDD and GAD, wherein main effects and two-way interactions of resilience and SLEs were significant, such that greater resilience was protective even in the context of high numbers of past-year SLEs. The three-way interaction was not significant, suggesting that the relationship between SLEs and resilience on psychopathology was the same for both men and women. Findings support the conceptualization of resilience as a buffer against the impact of future life stressors on common internalizing psychopathology. Longitudinal designs and trajectory-based studies that include recurring measures of SLEs could inform conceptualizations of resilience in the context of ongoing adversity and aid in developing interventions aimed at fostering healthy adaptation in the face of stressors.

The Nomological Network of a Behavioral Distress Tolerance Task in Veterans.

There is a relative lack of research on distress tolerance (DT) in veteran samples. The aims of the study were to (a) evaluate convergent and discriminant validity of a behavioral measure of DT compared to theoretically similar (i.e., self-report DT, negative urgency) and dissimilar (i.e., risk-taking) constructs and (b) evaluate the concurrent validity of DT in relation to posttraumatic stress disorder (PTSD) and depressive symptoms in a veteran sample. A sample of U.S. veterans who served after the September 11, 2001 terror attacks (N = 306, 89.9% male; M age 30.2 years, SD = 4.5, range: 21-40 years) completed self-report and behavioral measures of DT, risk-taking, impulsivity, and depressive symptoms, and completed a clinical interview for PTSD. Results of a multitrait-multimethod matrix found significant yet minimal shared variance, r2 = .01-.03, ps = .002-.055, between the self-report and behavioral measures of DT. We used a series of multiple regressions to examine the relative contribution of the behavioral and self-report DT measures in the prediction of PTSD and depressive symptoms. Self-reported, but not behavioral, DT accounted for unique variance in PTSD, r2 = .12, p < .001, and depressive symptoms, r2 = .23, p < .001. Participants with PTSD or higher scores on measures of depression were more likely to report greater increases in frustration and irritability after completing the behavioral task. Results indicate that DT is not a unidimensional construct and must be considered in the context of specific emotions (e.g., tolerance of irritability vs. fear) and contexts (e.g., behavioral, affective).

Replication of the Interaction of PRKG1 and Trauma Exposure on Alcohol Misuse in an Independent African American Sample.

In the present study, we sought to replicate recent findings of Polimanti et al. (2017), who conducted a genome-wide gene-by-environment interaction study (GEWIS) and identified a gene-by-trauma interaction that predicts alcohol misuse among African Americans.  Consistent with the findings published by Polimanti and colleagues, results of the current study demonstrated an interaction effect, b = 0.41, of trauma exposure and rs1729578 in the intron of PRKG1 on alcohol misuse in a subsample of ancestral African Americans. The minor allele (rs1729578*C) was positively associated with increased alcohol use disorder symptoms in trauma-exposed subjects and negatively associated in non-trauma-exposed subjects.  This effect, however, was only significant for one out of three alcohol outcome measures we investigated, suggesting the interaction may be most salient when predicting higher severity of alcohol misuse. Additionally, the effect did not remain significant after we accounted for testing the effect on three different outcome variables. Also in line with the original study, the gene-by-environment effect was not demonstrated among the ancestral European subsample.  The findings suggest this gene variant may increase an individual's susceptibility to environmental influences, both adverse and supportive.

Does Parenting Influence the Enduring Impact of Severe Childhood Sexual Abuse on Psychiatric Resilience in Adulthood?

This study examined the effect of parenting on the association between childhood sexual abuse (CSA) and psychiatric resilience in adulthood in a large female twin sample (n = 1423) assessed for severe CSA (i.e., attempted or completed intercourse before age 16). Severe CSA was associated with lower resilience to recent stressors in adulthood (defined as the difference between their internalizing symptoms and their predicted level of symptoms based on cumulative exposure to stressful life events). Subscales of the Parental Bonding Instrument were significantly associated with resilience. Specifically, parental warmth was associated with increased resilience while parental protectiveness was associated with decreased resilience. The interaction between severe CSA and parental authoritarianism was significant, such that individuals with CSA history and higher authoritarianism scores had lower resilience. Results suggest that CSA assessment remains important for therapeutic work in adulthood and that addressing parenting may be useful for interventions in children with a CSA history.

Examination of Racial Differences in a Posttraumatic Stress Disorder Group Therapy Program for Veterans.

Posttraumatic stress disorder (PTSD) is one of the most prevalent mental health diagnoses for veterans. Group therapy can be an effective and efficient means of treating PTSD, yet the literature exploring treatment outcomes for racial minorities is mixed and limited. The present study was an evaluation across racial groups of the PTSD Recovery Program, a manualized group therapy implemented at a Veterans Affairs hospital. Data were collected from male veterans (N = 450) who identified as non-Hispanic White or non-Hispanic African American and participated in a 10-week, combat-related, group therapy program between 2010 and 2014. Participants completed the Posttraumatic Stress Disorder Checklist-Military version (PCL-M) measure at pre-treatment and post-treatment. The Program led to a statistically significant reduction in PCL-M scores (Cohen's d = .64). Symptom reduction occurred regardless of race, with no racial differences in improvement. Racial and ethnic composition of groups was not related to outcomes. The Program was effective regardless of veteran group or provider. Results imply that the PTSD Recovery Program is an effective first-line option to treating non-Hispanic White and non-Hispanic African American veterans with PTSD. Future research should continue to explore the associations between group characteristics and treatment outcomes.

An examination of the etiologic overlap between the genetic and environmental influences on insomnia and common psychopathology.

BACKGROUND: Insomnia is comorbid with internalizing and externalizing psychiatric disorders. However, the extent to which the etiologic influences on insomnia and common psychopathology overlap is unclear. There are limited genetically informed studies of insomnia and internalizing disorders and few studies of overlap exist with externalizing disorders. METHODS: We utilized twin data from the Virginia Adult Twin Studies of Psychiatric and Substance Use Disorders (total n = 7,500). Insomnia, internalizing disorders (major depressive disorder [MDD], generalized anxiety disorder [GAD]), and alcohol abuse or dependence (AAD) were assessed at two time points, while antisocial personality disorder (ASPD) was assessed once. Cholesky decompositions were performed in OpenMx and longitudinal measurement models were run on available phenotypes to reduce measurement error. RESULTS: The latent additive genetic influences on insomnia overlapped significantly (56% for females, 74% for males) with MDD and were shared completely (100%) with GAD. There was significant overlap of latent unique environmental influences, with overlap ranging from 38 to 100% across disorders. In contrast, there was less genetic overlap between insomnia and externalizing disorders, with 18% of insomnia's heritability shared with AAD and 23% with ASPD. Latent unique environmental overlap between insomnia and both externalizing disorders was negligible. CONCLUSIONS: The evidence for substantial genetic overlap between insomnia and stable aspects of both internalizing disorders suggests that there may be few insomnia-specific genes and investigation into unique environmental factors is important for understanding insomnia development. The modest overlap between insomnia and externalizing disorders indicates that these disorders are genetically related, but largely etiologically distinct.

The Effects of a BDNF Val66Met Polymorphism on Posttraumatic Stress Disorder: A Meta-Analysis.

OBJECTIVE: Given evidence that posttraumatic stress disorder (PTSD) is moderately heritable, a number of studies utilizing candidate gene approaches have attempted to examine the potential contributions of theoretically relevant genetic variation. Some of these studies have found sup port for a brain-derived neurotrophic factor (BDNF) variant, Val66Met, in the risk of developing PTSD, while others have failed to find this link. METHODS: This study sought to reconcile these conflicting findings using a meta-analysis framework. Analyses were also used to determine whether there is significant heterogeneity in the link between this variant and PTSD. We conducted a systematic review of the literature on BDNF and PTSD from the PsycINFO and PubMed databases. A total of 11 studies were included in the analysis. RESULTS: Findings indicate a marginally significant effect of the BDNF Val66Met variant on PTSD (p < 0.1). However, of the 11 studies included, only 2 suggested an effect with a non-zero confidence interval, one of which showed a z score of 3.31. We did not find any evidence for heterogeneity. CONCLUSIONS: Findings from this meta-analytic investigation of the published literature provide little support for the Val66Met variant of BDNF as a predictor of PTSD. Future well-powered agnostic genome-wide association studies with more refined phenotyping are needed to clarify genetic influences on PTSD.

Association of Posttraumatic Stress Disorder With rs2267735 in the ADCYAP1R1 Gene: A Meta-Analysis.

Recent studies point to the potential role of the (pituitary) adenylate cyclase activating polypeptide receptor 1 (ADCYAP1R1) gene, which has been implicated in stress response, in posttraumatic stress disorder (PTSD). Multiple genetic association studies have examined potential PTSD risk related to this gene, with mixed results. We conducted a meta-analysis of rs2267735 in ADCYAP1R1 in PTSD. A literature search was conducted using PubMed and PsycINFO, resulting in nine studies that met criteria for inclusion in analysis. Biostat's Comprehensive Meta-Analysis was used to conduct the main meta-analysis on the combined sex sample, as well as two subanalyses examining effects separately in female and male participants. Results indicated that the C allele of rs2267735 conferred significant risk for PTSD in the combined sex data, OR = 1.210, 95% CI [1.007, 1.454], p = .042, and in the subsample of women and girls, OR = 1.328, 95% CI [1.026, 1.719], p = .031; but not in the subsample of men and boys, OR = 0.964, 95% CI [0.733, 1.269], p = .796. These results provide evidence for an association between ADCYAP1R1 and PTSD and indicate that there may indeed be sex differences. Implications of these findings, including the role of rs2267735 as one modulator of the stress system, are discussed.

The relationship between genetic and environmental influences on resilience and on common internalizing and externalizing psychiatric disorders.

PURPOSE: Resilience to stressful life events (SLEs), which increase risk of psychopathology, is influenced by genetic factors. The purpose of this paper was to map the overlap of etiologic risk factors for resilience onto the broad psychopathological map. Resilience was defined as the difference between the twins' total score on a broad measure of internalizing symptoms and their predicted score based on their cumulative exposure to SLEs. METHODS: Cholesky decompositions were performed with OpenMx to quantify the overlap in genetic and environmental risk factors between resilience and four phenotypes [major depression (MD), generalized anxiety disorder (GAD), alcohol abuse or dependence (AAD), and antisocial personality disorder (ASPD)]. RESULTS: The genetic factors that influence resilience account for 42 and 61 % of the heritability of MD and GAD, respectively, and 20 and 18 % for AAD and ASPD, respectively. The latent genetic contribution to MD was shared 47 % with resilience, and for AAD, this estimate was lower (23 %). The shared environmental covariance was nominal. CONCLUSIONS: Genetic influences on resilience contribute to internalizing phenotypes to a higher degree than to externalizing phenotypes. Environmental influences can also have an enduring effect on resilience. However, virtually all of the covariance between resilience and the phenotypes was genetic.

A Narrative Commentary on the Use of a Rational Emotive Behavior Therapy-Informed Group to Address Irrational Beliefs, Posttraumatic Stress Disorder, and Comorbidities.

Irrational beliefs of Demandingness, Catastrophizing, Low Frustration Tolerance, and Depreciation have demonstrated prevalence in disparate areas of life, including psychopathology, the military, politics, religion, and education. Individuals with mental health concerns, such as Post-Traumatic Stress Disorder (PTSD), endorse elevations in such thoughts compared to the general population. This commentary describes the rationale for focusing on irrational beliefs in efforts to address PTSD and presents the Rational Emotive Behavior Therapy (REBT)-Informed Group for PTSD as a potential novel application of a well-established intervention. In support of these suggestions, we present a narrative review of the published work on irrational beliefs and REBT tenets as relevant for PTSD. We then introduce and describe the REBT-Informed Group intervention, summarize the prior preliminary research conducted by our group, and present some novel data from a re-analysis of this prior work. We end with commentary related to future directions of REBT approaches for PTSD to address limitations and expand the impact of the treatment to military and other Veteran or civilian populations.