Dataset Information

Negative Urgency Mediates the Relation between Genetically-Influenced Serotonin Functioning and Alcohol Problems.

ABSTRACT: Serotonin (5-HT) functioning is associated with alcohol problems. However, the mechanisms underlying this association remain unclear. The current study tested whether five separate dimensions of impulsivity (UPPS-P) mediated the relation between a polygenic score indexing 5-HT functioning and alcohol problems and whether any of these paths were moderated by age. Results showed that a 5-HT polygenic score predicted alcohol problems indirectly through negative urgency, but not any other facet of impulsivity. The 5-HT polygenic score also directly predicted alcohol problems. No age moderation was found. Findings suggest that negative urgency might be one important mechanism underlying the relation between genetically-influenced 5-HT functioning and alcohol problems. However, genetically-influenced 5-HT functioning likely influences alcohol problems through additional mechanisms. More broadly, results suggest that the previously observed transdiagnostic nature of 5-HT functioning on diverse types of psychopathology might be, in part, explained by its effect on negative urgency.

SUBMITTER: Wang FL

PROVIDER: S-EPMC5773057 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Negative Urgency Mediates the Relation between Genetically-Influenced Serotonin Functioning and Alcohol Problems.

Wang Frances L FL Chassin Laurie L

Clinical psychological science : a journal of the Association for Psychological Science 20171006 1

Serotonin (5-HT) functioning is associated with alcohol problems. However, the mechanisms underlying this association remain unclear. The current study tested whether five separate dimensions of impulsivity (UPPS-P) mediated the relation between a polygenic score indexing 5-HT functioning and alcohol problems and whether any of these paths were moderated by age. Results showed that a 5-HT polygenic score predicted alcohol problems indirectly through negative urgency, but not any other facet of i ...[more]

PMID: 29354329

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Project description:BackgroundUp to 50% of individuals with posttraumatic stress disorder (PTSD) endorse problematic alcohol use. Typically, these individuals present with more complex and often more severe PTSD symptoms than those who do not report problematic alcohol use. Emerging literature suggests that heightened symptoms of dissociation are likewise associated with greater PTSD symptom severity. Despite this knowledge, the role of dissociation in the relation between PTSD severity and alcohol-related problems has yet to be examined. Here, we explore the mediating role of dissociative symptomatology on the association between PTSD severity and alcohol-related problems within a PTSD treatment-seeking sample.MethodsStructural equation modeling was used to test the mediating role of dissociative symptomatology between PTSD severity and alcohol-related problems. Participants [N = 334; mean age (SD) = 44.29 (9.77), 50% female] were drawn from a clinical intake battery database for PTSD in-patient treatment services at Homewood Health Care, Guelph, ON, Canada. A subset of battery measures assessing PTSD severity, dissociative symptomatology, and alcohol-related problems were submitted to analysis.ResultsA significant positive association emerged between PTSD severity and alcohol-related problems (β = 0.127, p < 0.05) in the absence of dissociative symptomatology. Critically, however, when added to this model, dissociative symptomatology (six unique facets of dissociation assessed by the Multiscale Dissociation Inventory) mediated the relation between PTSD severity and alcohol-related problems. Specifically, greater PTSD severity was associated with greater dissociative symptomatology (β = 0.566, p < 0.0001), which was in turn associated with greater alcohol-related problems (β = 0.184, p < 0.05).ConclusionsThese results suggest that dissociative symptomatology plays a key role in explaining the relation between PTSD severity and alcohol-related problems. Future studies should examine the impact of targeting dissociative symptomatology specifically in treating individuals with PTSD who endorse alcohol-related problems.

Project description:In 1990, Blum and colleagues first reported an association between DRD2 and alcoholism. While there have been subsequent replications of this genetic association, there have also been numerous studies that failed to detect an association between DRD2 and alcohol dependence. We propose that one aspect contributing to this inconsistency is the variation in alcohol phenotype used across studies. Within the population-based Finnish twin sample, FinnTwin16, we previously performed multivariate twin analyses to extract latent genetic factors, which account for the variation across seven measures of alcohol consumption (frequency of drinking, frequency?×?quantity, frequency of heavy drinking, frequency of intoxication and maximum drinks in a 24-hour period) and problems (the Rutgers Alcohol Problem Index-RAPI and the Mälmö-modified Michigan Alcohol Screen Test-MmMAST) in 3065 twins. In the present study, we examined the association between 31 DRD2/ANKK1 single-nucleotide polymorphisms (SNPs) and the genetic factor scores generated by twin analyses in a subset of FinnTwin16 (n?=?602). We focus on two of the genetic factors: a general alcohol consumption and problems factor score, which represents shared genetic variance across alcohol measures, and a alcohol problems genetic factor score, which loads onto the two indices of problematic drinking (MAST and RAPI). After correction for multiple testing across SNPs and phenotypes, of the 31 SNPs genotyped across DRD2/ANKK1, one SNP (rs10891549) showed significant association with the general alcohol consumption and problems factor score (P?=?0.004), and four SNPs (rs10891549, rs1554929, rs6275, rs6279), representing two independent signals after accounting for linkage disequilibrium, showed significant association with the alcohol problems genetic factor score (P?=?0.005, P?=?0.005, P?=?0.003, P?=?0.003). In this study, we provide additional positive evidence for the association between DRD2/ANKK1 and alcohol outcomes, including frequency of drinking and drinking problems. Additionally, post hoc analyses indicate stronger association signals using genetic factor scores than individual measures, which suggest that accounting for the genetic architecture of the alcohol measures reduces genetic heterogeneity in alcohol dependence outcomes in this sample and enhances the ability to detect association.

Dataset Information

Negative Urgency Mediates the Relation between Genetically-Influenced Serotonin Functioning and Alcohol Problems.

Publications

Negative Urgency Mediates the Relation between Genetically-Influenced Serotonin Functioning and Alcohol Problems.

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