Kaitlin Bountress

The genetics and epigenetics of PTSD: overview, recent advances, and future directions

This paper provides a brief summary and commentary on the growing literature and current developments related to the genetic underpinnings of posttraumatic stress disorder (PTSD). We first briefly provide an overview of the behavioral genetic literature on PTSD, followed by a short synopsis of the substantial candidate gene literature with a focus on genes that have been meta-analyzed. We then discuss the genome-wide association studies (GWAS) that have been conducted, followed by an introduction to other molecular platforms used in PTSD genomic studies, such as epigenetic and expression approaches. We close with a discussion of developments in the field that include the creation of the PTSD workgroup of the Psychiatric Genomics Consortium, statistical advances that can be applied to GWAS data to answer questions of heritability and genetic overlap across phenotypes, and bioinformatics techniques such as gene pathway analyses which will further advance our understanding of the etiology of PTSD.

Personalizing substance use treatment based on pre-treatment impulsivity and sensation seeking: A review

BACKGROUND Theoretically, substance use disorder (SUD) treatment that matches an individuals etiology and/or maintaining factors should be more effective than a treatment that does not directly address these factors. Impulsivity and sensation/reward seeking may contribute to the development and maintenance of SUDs, and are potential candidate variables for assigning patients to treatment. The goal is to identify whether current research can provide insight into which treatments may be most effective for individuals high in impulsivity or sensation seeking, relative to other treatments. A secondary goal is to provide recommendations for personalizing SUD treatment based on etiology or maintaining factors. METHOD This review summarizes clinical trials that speak to the differential effectiveness of two or more treatments for alcohol, tobacco, and other drug use disorders, based on pre-treatment impulsivity, sensation seeking, or related constructs. RESULTS Few studies examine the differential effectiveness of two or more treatments for individuals high in impulsivity or sensation seeking. Very preliminary evidence suggests that contingency management may hold promise for individuals high in impulsivity. Pharmacological trials were under-represented in the current review, despite evidence that the effectiveness of some pharmacological interventions may be moderated by impulsivity. CONCLUSIONS Potential reasons for slow rate of progress to date are provided. Given slow accumulation of evidence, an alternative method for personalizing treatment based on pre-treatment psychosocial factors, including impulsivity and sensation/reward seeking, is proposed. Future research may explore the role of contingency management for SUD among individuals with high pre-treatment impulsivity or sensation seeking. Finally, novel, technology-enhanced behavioral mechanisms are discussed as an adjunct to SUD treatment for these high-risk populations.

Parent and peer influences on emerging adult substance use disorder: A genetically informed study.

The present study utilizes longitudinal data from a high-risk community sample to examine the unique effects of genetic risk, parental knowledge about the daily activities of adolescents, and peer substance use on emerging adult substance use disorders (SUDs). These effects are examined over and above a polygenic risk score. In addition, this polygenic risk score is used to examine gene-environment correlation and interaction. The results show that during older adolescence, higher adolescent genetic risk for SUDs predicts less parental knowledge, but this relation is nonsignificant in younger adolescence. Parental knowledge (using mother report) mediates the effects of parental alcohol use disorder (AUD) and adolescent genetic risk on risk for SUD, and peer substance use mediates the effect of parent AUD on offspring SUD. Finally, there are significant gene-environment interactions such that, for those at the highest levels of genetic risk, less parental knowledge and more peer substance use confers greater risk for SUDs. However, for those at medium and low genetic risk, these effects are attenuated. These findings suggest that the evocative effects of adolescent genetic risk on parenting increase with age across adolescence. They also suggest that some of the most important environmental risk factors for SUDs exert effects that vary across level of genetic propensity.

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

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. Biostats 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.

An examination of the impact of maladaptive coping on the association between stressor type and alcohol use in college

ABSTRACT Objective: Examine the impact of maladaptive coping style on the association between source of stress (academic, interpersonal, intrapersonal, environmental) and alcohol use (consumption, heavy episodic drinking, driving under the influence) among college students. Participants: 1,027 college students completed an online survey in April 2014. Methods: To test the mediating effects of maladaptive coping on the association between academic stress and alcohol use variables, indirect effects were examined using the PROCESS analytical framework for SPSS. Results: Maladaptive coping and academic stress were associated with alcohol use outcomes. Moreover, maladaptive coping mediated the relationship between academic stress and two of three alcohol use outcomes (consumption, heavy episodic drinking). Conclusions: Among college students, the association between academic stress and alcohol use may be driven by maladaptive coping. College students may benefit from interventions that seek to improve coping skills, potentially alleviating the burden of academic stress and decreasing problematic alcohol use.

Impulsivity and Comorbid PTSD-Binge Drinking

Abstract Objective: Trauma exposure is common, with estimates of 28% to 90% of adults reporting at least one traumatic event over their lifetime. Those exposed to traumatic events are at risk for alcohol misuse (i.e., binge drinking), posttraumatic stress disorder (PTSD), or both. A potential underlying mechanism for this comorbidity is increased impulsivity—the tendency to act rashly. Little work to date has examined the impact of different impulsogenic traits on this comorbidity. Methods: This study (n = 162) investigated trauma-exposed young adults (aged 21–30) who had endorsed a lifetime interpersonal trauma. In addition, three impulsogenic traits (motor, nonplanning, and attentional) were measured. Results: Over and above the covariates for age, gender, race, and traumatic events, greater attentional impulsivity was associated with greater likelihood of meeting criteria for PTSD and binge drinking, compared to meeting criteria for PTSD, binge drinking, or neither. Neither nonplanning impulsivity nor motor impulsivity exerted unique effects. Conclusions: Young adults who report difficulty attending to immediate stimuli within their environment may be unable to think about and/or process the traumatic event, potentially increasing risk for PTSD and maladaptive coping skills to manage this distress (e.g., alcohol misuse, binge drinking).

Genetic and psychosocial predictors of alcohol use trajectories among disaster-exposed adolescents

BACKGROUND AND OBJECTIVES Adolescent alcohol misuse is associated with numerous long-term adverse outcomes, so we examined predictors of alcohol use among disaster-exposed adolescents, a group at-risk for alcohol misuse. METHODS The current study (n = 332) examined severity of tornado-related exposure, posttraumatic stress disorder (PTSD) symptoms, emotional support, and a genetic risk sum score (GRSS) as predictors of alcohol use trajectories. RESULTS Severity of exposure interacted with the GRSS to predict both intercept (12-month follow up quantity of alcohol use) and growth rate. Emotional support also interacted with adolescent PTSD symptoms to predict intercept and growth rate. DISCUSSION AND CONCLUSIONS Adolescents with greater severity of disaster exposure and high genetic risk comprise a high risk group, on which efforts to prevent alcohol use should be focused. Additionally, emotional support is essential in buffering the effects of PTSD symptoms on alcohol use outcomes among adolescents. SCIENTIFIC SIGNIFICANCE Toward the aim of reducing adolescent alcohol misuse following disaster exposure, there is utility in inserting immediate supports (e.g., basic resources) into communities/families that have experienced significant disaster-related severity, particularly among adolescents at high levels of genetic risk for alcohol use/misuse. Additionally, prevention efforts aimed at improving emotional supports for adolescents with more PTSD symptoms may reduce propensity for alcohol misuse following disaster. This information can be easily incorporated into existing web-based interventions. (Am J Addict 2017;26:623-631).

Associations among impulsivity, trauma history, and alcohol misuse within a young adult sample

OBJECTIVE Young adult alcohol misuse is associated with numerous long-term adverse outcomes. Given the link between impulsivity and alcohol use, we examined whether three impulsivity-related traits differentially predicted number of drinks per drinking day (DDD). We also examined whether these effects varied for those with different trauma histories. METHOD The current study (n=254) examined motor, non-planning, and attentional impulsivity as predictors of DDD. It also examined whether impulsivity was differentially predictive of DDD across individuals in: a control group (non-trauma exposed), a trauma exposed but non-PTSD group, and a PTSD group. RESULTS Regardless of group, more motor impulsivity was associated with more DDD. The effect of non-planning impulsivity varied according to trauma history. Specifically, more non-planning impulsivity predicted more DDD for those without PTSD. Finally, attentional impulsivity was not predictive of DDD. CONCLUSIONS Young adults with high levels of motor impulsivity, regardless of trauma history, may be a particularly high-risk group in terms of propensity for alcohol use/misuse. Additionally, high levels of non-planning impulsivity may signify those at greater risk for alcohol misuse, among those without PTSD. Motor impulsivity and non-planning impulsivity may serve as useful intervention targets in alcohol misuse prevention efforts. Implications for future research in this area are discussed.

Reducing sexual risk behaviors: secondary analyses from a randomized controlled trial of a brief web-based alcohol intervention for underage, heavy episodic drinking college women

Abstract Background: Alcohol use and sexual risk behaviors (SRBs) are significant problems on college campuses. College women are at particularly high risk for negative consequences associated with sexually transmitted infections (STIs) and unwanted pregnancy. Methods: The current study (n = 160) examined the effect of a brief, web-based alcohol intervention (n = 53) for college women on reducing SRBs compared to an assessment only control (n = 107) with a randomized controlled trial. Outcome measures included condom use assertiveness and number of vaginal sex partners and data were collected at baseline and three-month follow-up. Results: Regression analyses revealed that the alcohol intervention was associated with higher levels of condom use assertiveness at a three-month follow-up. Additionally, more alcohol use was associated with less condom use assertiveness for those with more significant sexual assault histories. Conclusions: These findings suggest that alcohol interventions may impact college women’s beliefs but not behavior, and future interventions should more explicitly target both alcohol and sexual risk to decrease risky behaviors.

GxE effects of FKBP5 and traumatic life events on PTSD: A meta-analysis

BACKGROUND Twin studies have demonstrated that both genetic and environmental factors influence risk for posttraumatic stress disorder (PTSD), and there is some evidence supporting the interplay of genes and environment (GxE). Many GxE studies within the PTSD literature have focused on genes implicated in the stress response system, such as FK506 binding protein 51 (FKBP5). Given inconsistencies across GxE literature as a whole, a meta-analysis to synthesize results is warranted. METHODS Studies were identified through PubMed and PsycINFO. A meta-analysis was conducted using a random effects model in the MAc package in R. Heterogeneity of the effect size distribution was examined with Cochrans Q statistic. A Simes procedure was used to test the gene-level GxE effect for FKBP5 interacting with trauma. RESULTS A significant gene-level GxE gene effect was demonstrated for FKBP5 when pooled across all four examined variants (rs1360780, rs3800373, rs9296158, rs9470080) when interacting with trauma exposure on PTSD. Significant large GxE effect sizes were also found for each independent variant. There was no evidence for heterogeneity of variance. LIMITATIONS Limitations include reduced power for detecting variability across moderators, potential bias due to failure of meta-analyzed studies to account for two-way covariate x gene and covariate x environment influences, and a high false discovery rate that is characteristic of GxE analyses. CONCLUSIONS This is the first study to quantify an overall gene-level effect of FKBP5 in a GxE analysis of PTSD, evidence which may be used to address current issues in the FKBP5 GxE literature (e.g., disparate variants, low sample sizes and power), as well as inform follow-up functional research.