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Amygdala-orbitofrontal functional connectivity mediates the relationship between sensation seeking and alcohol use among binge-drinking adults.

ABSTRACT: BACKGROUND:Decreased amygdala-orbitofrontal cortex (OFC) neural functional connectivity (FC) positively predicts alcohol use among adolescents. Low amygdala-OFC FC is also associated with poor emotion regulation, a trait robustly linked to alcohol use. Thus, decreased amygdala-OFC connectivity may represent a risk factor for the development of alcohol use disorder (AUD) via impaired emotion regulation or reward processing. In this study, we examined amygdala-OFC FC among young adult binge drinkers at high risk for AUD. We also tested if amygdala-OFC FC mediates the relationship between externalizing personality traits and alcohol use. METHODS:Healthy male and female (n?=?39) binge drinkers completed a resting state fMRI scan and the Eysenck Impulsive Personality questionnaire. We utilized seed-based connectivity of the left and right amygdala to prefrontal regions as well as mediation analysis. RESULTS:Individuals with higher weekly alcohol use displayed decreased right amygdala-OFC FC. Furthermore, high trait venturesomeness, but not impulsivness, was associated with decreased right amygdala-OFC FC. Finally, right amygdala-OFC FC mediated the relationship between trait venturesomeness and weekly drinking; individuals with high trait venturesomeness displayed decreased right amygdala-OFC FC, which in turn predicted greater weekly drinking. CONCLUSIONS:Our findings corroborate and extend the adolescent literature by showing that decreased amygdala-OFC FC is associated with higher alcohol consumption among adults at elevated risk for AUD. This study also demonstrates for the first time that this neural profile reflects a tendency to sensation seeking. In sum, our findings suggest that amygdala-OFC FC may be an objective neural target for alcohol use prevention and intervention.

SUBMITTER: Crane NA

PROVIDER: S-EPMC6800008 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Project description:The objective of this study was to determine changes in gene expression within the extended amygdala following binge-like alcohol drinking by adolescent alcohol-preferring (P) rats. Starting at 28 days of age, P rats were given concurrent access to 15 and 30 % ethanol for 3 one-h sessions for 5 consecutive days each week until they were 49 days old. Rats were killed by decapitation 3 h after the first ethanol access session on the 15th day of drinking. RNA was prepared from micropunch samples of the nucleus accumbens shell (Acb-sh) and central nucleus of the amygdala (CeA). Ethanol intakes were 2.5 to 3.0 g/kg/session. There were 154 and 182 unique named genes that significantly differed (FDR = 0.2) between the water and ethanol group in the Acb-sh and CeA, respectively. Gene Ontology (GO) analyses indicated that adolescent binge drinking produced changes in the in biological processes involved in cell proliferation and regulation of cellular structure in the Acb-sh, and in neuron projection and positive regulation of cellular organization in the CeA. Ingenuity Pathway Analysis indicated that, in the Acb-sh, there were several major intracellular signaling pathways (e.g., cAMP-mediated and protein kinase A signaling pathways) altered by adolescent drinking, with 3-fold more genes up-regulated than down-regulated in the alcohol group. The cAMP-mediated signaling system was also up-regulated in the CeA of the alcohol group. Weighted gene co-expression network analysis (WGCNA) indicated significant G-protein coupled receptor signaling and transmembrane receptor protein kinase signaling categories in the Acb-sh and CeA, respectively. Overall, the results of this study indicated that binge-like alcohol drinking by adolescent P rats is differentially altering the expression of genes in the Acb-sh and CeA, some of which are involved in intracellular signaling pathways and may produce long-term changes in neuronal function. Differences in gene expression in the central nucleus of the amygdala (CeA) were compared in two groups of alcohol-preferring (P) rats, one given water only and the other given access to 15 & 30% ethanol during adolescence.

Project description:Excessive consumption of alcohol is a major problem in the United States and abroad. Despite many years of study, it is unclear why some individuals drink alcohol excessively while others do not. It has been postulated that either lower or greater acute responses to alcohol, or both, depending on the limb of the breath alcohol concentration curve, contribute to propensity for alcohol misuse.To prospectively assess the relationship of acute alcohol responses to future binge drinking.Within-subject, double-blind, placebo-controlled, multidose laboratory alcohol challenge study with intensive follow-up. Each participant completed 3 randomized sessions examining responses to a high (0.8 g/kg) and low (0.4 g/kg) alcohol dose and placebo, followed by quarterly assessments for 2 years examining drinking behaviors and alcohol diagnoses.Participants recruited from the community.High-risk heavy social drinkers aged 21 to 35 years who habitually engage in weekly binge drinking (n = 104) and light drinker controls (n = 86).We conducted 570 laboratory sessions with a subsequent 99.1% follow-up (1506 of 1520).Biphasic Alcohol Effects Scale, Drug Effects Questionnaire, cortisol response, Timeline Follow-Back, Drinker Inventory of Consequences-Recent, and DSM-IV alcohol abuse and dependence.Alcohol produced greater stimulant and rewarding (liking and wanting) responses and lower sedative and cortisol responses in heavy vs light drinkers. Among the heavy drinkers, greater positive effects and lower sedative effects after alcohol consumption predicted increased binge drinking frequency during follow-up. In turn, greater frequency of binge drinking during follow-up was associated with greater likelihood of meeting diagnostic criteria for alcohol abuse and dependence.The widely held low level response theory and differentiator model should be revised: in high-risk drinkers, stimulant and rewarding alcohol responses even at peak breath alcohol concentrations are important predictors of future alcohol problems.clinicaltrials.gov Identifier: NCT00961792.

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Amygdala-orbitofrontal functional connectivity mediates the relationship between sensation seeking and alcohol use among binge-drinking adults.

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