Dataset Information

Evidence of Shared Genome-Wide Additive Genetic Effects on Interpersonal Trauma Exposure and Generalized Vulnerability to Drug Dependence in a Population of Substance Users.

ABSTRACT: Exposure to traumatic experiences is associated with an increased risk for drug dependence and poorer response to substance abuse treatment (Claus & Kindleberger, 2002; Jaycox, Ebener, Damesek, & Becker, 2004). Despite this evidence, the reasons for the observed associations of trauma and the general tendency to be dependent upon drugs of abuse remain unclear. Data (N = 2,596) from the Study of Addiction: Genetics and Environment were used to analyze (a) the degree to which commonly occurring single nucleotide polymorphisms (SNPs; minor allele frequency > 1%) in the human genome explains exposure to interpersonal traumatic experiences, and (b) the extent to which additive genetic effects on trauma are shared with additive genetic effects on drug dependence. Our results suggested moderate additive genetic influences on interpersonal trauma, h(2) SNP-Interpersonal = .47, 95% confidence interval (CI) [.10, .85], that are partially shared with additive genetic effects on generalized vulnerability to drug dependence, h(2) SNP-DD = .36, 95% CI [.11, .61]; rG-SNP = .49, 95% CI [.02, .96]. Although the design/technique does not exclude the possibility that substance abuse causally increases risk for traumatic experiences (or vice versa), these findings raise the possibility that commonly occurring SNPs influence both the general tendency towards drug dependence and interpersonal trauma.

SUBMITTER: Palmer RH

PROVIDER: S-EPMC6344111 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Evidence of Shared Genome-Wide Additive Genetic Effects on Interpersonal Trauma Exposure and Generalized Vulnerability to Drug Dependence in a Population of Substance Users.

Palmer Rohan H C RH Nugent Nicole R NR Brick Leslie A LA Bidwell Cinnamon L CL McGeary John E JE Keller Matthew C MC Knopik Valerie S VS

Journal of traumatic stress 20160523 3

Exposure to traumatic experiences is associated with an increased risk for drug dependence and poorer response to substance abuse treatment (Claus & Kindleberger, 2002; Jaycox, Ebener, Damesek, & Becker, 2004). Despite this evidence, the reasons for the observed associations of trauma and the general tendency to be dependent upon drugs of abuse remain unclear. Data (N = 2,596) from the Study of Addiction: Genetics and Environment were used to analyze (a) the degree to which commonly occurring si ...[more]

PMID: 27214850

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Project description:BackgroundThe aim of this study was to systematically summarize knowledge on the association between exposure to interpersonal trauma and addictive behaviors. Extant reviews on this association focused on a restricted range of substance-related addictions, and/or used a narrative instead of a systematic approach.MethodsSystematic searches of 8 databases yielded 29,841 studies, of which 3054 studies were included and subsequently classified in relation to study design (scoping review). A subset of observational studies (N = 181) prospectively investigating the relationship between exposure to interpersonal traumata and subsequent behavioral or substance-related addiction problems were characterized. Heterogeneity in study methodologies and types of addictive behaviors and traumatic experiences assessed precluded meta-analysis. Instead, the proportions of associations tested in this literature that revealed positive, negative, or null relationships between trauma exposure and subsequent addictive behaviors were recorded, along with other methodological features.ResultsOf 3054 included studies, 70.7% (n = 2160) used a cross-sectional design. In the 181 prospective observational studies (407,041 participants, 98.8% recruited from developed countries), 35.1% of the tested associations between trauma exposure and later addictive behaviors was positive, 1.3% was negative, and 63.6% was non-significant. These results were primarily obtained among non-treatment seeking samples (80.7% of studies; n = 146), using single and multi-item measures of addictive behaviors of unknown psychometric quality (46.4% of studies). Positive associations were more frequently observed in studies examining childhood versus adult traumatization (39.7% vs. 29.7%).ConclusionsLongitudinal research in this area emphasizes alcohol abuse, and almost no research has examined behavioral addictions. Results provide some support for a positive association between exposure to interpersonal trauma and subsequent addictive behaviors but this relationship was not consistently reported. Longitudinal studies typically assessed trauma exposure retrospectively, often after addictive behavior onset, thus precluding robust inferences about whether traumatization affects initial onset of addictive behaviors.

Project description:BackgroundWhile post-traumatic stress disorder (PTSD) is defined by behavioral/cognitive symptoms most directly relevant to brain function, it can be considered a systemic disorder characterized by a distinct inability to reinstate homeostasis after trauma.MethodsIn this study, we conducted a secondary analysis of gene expression profiles in key PTSD-relevant tissues, namely blood, amygdala, and hippocampus, from a rat model of PTSD, to identify sex-specific and shared processes associated with individual differences in response to recent trauma exposure.ResultsOur findings suggest both shared and sex-specific mechanisms underlying individual differences associated with vulnerability and resilience to trauma in hippocampus, amygdala, and blood. By disentangling cell composition from transcriptional changes, we found higher proportions of hippocampal oligodendrocytes in the PTSD-like, extreme behavioral response (EBR) group for both sexes and also identified modules for transcriptional activity associated with group differences (i.e., response to trauma) in the hippocampus that appeared to be sex-specific. By contrast, we found prominent sex differences, but no group differences, in amygdalar cell composition, and both shared and sex-specific modules representing PTSD-relevant transcriptional activity in the amygdala. Across amygdala and hippocampus, both sex-specific and shared processes were relevant to an overarching framework for EBR implicating disrupted TNFα/NFκΒ signaling and excitatory/inhibitory imbalance in dysregulated synaptic/structural plasticity with important implications for fear learning and memory. Our main finding in peripheral blood was consistent with the human literature and identified wound healing processes and hemostasis to be upregulated in the resilient, minimal behavioral response (MBR) group across sexes, but disrupted in a sexually dimorphic manner in the EBR group.ConclusionIn contrast to the varied characterization of the PTSD-like EBR group, characterization of MBR across blood, amygdala, and hippocampus suggests a common theme of upregulated wound healing and extracellular matrix (ECM) remodeling shared between sexes. In all, we identified differential oligodendrocyte proportions in hippocampus between PTSD-like EBR and resilient MBR, and identified processes and pathways that characterize the EBR and MBR-associated transcriptional changes across hippocampus, amygdala, and blood. The sex-specific mechanisms involved in EBR may contribute to the pronounced disparity in risk for PTSD, with women much more likely to develop PTSD.

Dataset Information

Evidence of Shared Genome-Wide Additive Genetic Effects on Interpersonal Trauma Exposure and Generalized Vulnerability to Drug Dependence in a Population of Substance Users.

Publications

Evidence of Shared Genome-Wide Additive Genetic Effects on Interpersonal Trauma Exposure and Generalized Vulnerability to Drug Dependence in a Population of Substance Users.

Similar Datasets

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