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Behavioral and neural sensitivity to uncertain threat in individuals with alcohol use disorder: Associations with drinking behaviors and motives.

ABSTRACT: A developing theory is that individuals with alcohol use disorder (AUD) display exaggerated reactivity to threats that are uncertain (U-threat), which facilitates excessive drinking as a means of avoidance-based coping. There is a promising initial behavioral evidence supporting this theory; however, the neural bases of reactivity to U-threat in individuals with AUD have not been examined. The extent to which biomarkers of U-threat reactivity map onto drinking behaviors and coping motives for alcohol use is also unknown. The current study therefore examined group differences in behavioral and neural reactivity to U-threat in adults with and without AUD. The study also tested whether behavior and brain responses to U-threat correlate with problematic drinking and coping motivated drinking. Volunteers (n = 65) with and without a history of AUD (38 AUD, 27 controls) were included and completed a well-validated threat-of-shock task to probe responses to U-threat and predictable threat (P-threat) while startle eyeblink potentiation was collected. Individuals also completed a newly designed, analogous version of the task during functional magnetic resonance imaging (fMRI). Results indicated that individuals with AUD displayed greater startle magnitude during U-threat, but not P-threat, and greater right insula and dorsal anterior cingulate cortex (dACC) activation during both forms of threat compared with controls. Startle magnitude and insula activation during U-threat positively correlated with self-reported problem drinking and coping motives for alcohol use. Findings demonstrate that individuals with AUD display exaggerated sensitivity to U-threat at the behavioral and neural level and that these multimethod biomarkers tap into negative reinforcement processes of alcohol abuse.

SUBMITTER: Gorka SM

PROVIDER: S-EPMC6898728 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and aimsEmerging evidence suggests that solitary drinking may be an important early risk marker for alcohol use disorder. The current paper is the first meta-analysis and systematic review on adolescent and young adult solitary drinking to examine associations between solitary drinking and increased alcohol consumption, alcohol problems, and drinking to cope motives.MethodsPsychINFO, PubMed, and Google Scholar were searched using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology and a pre-registered International Prospective Register of Systematic Reviews (PROSPERO) protocol (no. CRD42020143449). Data from self-report questionnaires regarding negative correlates of solitary drinking (e.g. alcohol problems) and solitary drinking motives (e.g. drinking to cope) were pooled across studies using random-effects models. Studies included adolescents (aged 12-18 years) and young adults (mean age between 18 and 30 years or samples with the majority of participants aged 30 years or younger).ResultsMeta-analytical results from 21 unique samples including 28,372 participants showed significant effects for the associations between solitary drinking and the following factors: increased alcohol consumption, r = 0.23, 95% confidence interval (CI) = 0.12, 0.33; drinking problems, r = 0.23, 95% CI = 0.13, 0.32; negative affect, r = 0.21, 95% CI = 0.16, 0.26; social discomfort, r = 0.17, 95% CI = 0.06, 0.27; negative reinforcement, r = 0.28, 95% CI = 0.24, 0.31; and positive reinforcement, r = 0.10, 95% CI = 0.03, 0.17. These associations were not moderated by age group (i.e. adolescent versus young adult), study quality, or differing solitary drinking definitions. Accounting for publication bias increased the effect sizes from r = 0.23 to 0.34 for alcohol consumption and from r = 0.23 to 0.30 for drinking problems, and lowered it from r = 0.10 to 0.06 and r = 0.17 to 0.11 for positive reinforcement and social discomfort, respectively.ConclusionsSolitary drinking among adolescents and young adults appears to be associated with psychosocial/alcohol problems and drinking to cope motives.

Project description:Highlights • Associations between alcohol drinking and pain sensitivity change over time.• Alcohol withdrawal-induced changes in ERK phosphorylation depend on pain status.• Exposure to both alcohol and pain synchronize brain glucocorticoid signaling. Alcohol use disorder (AUD) is a chronic, relapsing psychiatric disorder that is characterized by the emergence of negative affective states. The transition from recreational, limited intake to uncontrolled, escalated intake is proposed to involve a transition from positive to negative reinforcement mechanisms for seeking alcohol. Past work has identified the emergence of significant hyperalgesia/allodynia in alcohol-dependent animals, which may serve as a key negative reinforcement mechanism. Chronic pain has been associated with enhanced extracellular signal-regulated kinase (ERK) activity in cortical and subcortical nociceptive areas. Additionally, both pain and AUD have been associated with increased activity of the glucocorticoid receptor (GR), a key mediator of stress responsiveness. The objectives of the current study were to first determine relationships between thermal nociceptive sensitivity and alcohol drinking in male Wistar rats. While inflammatory pain induced by complete Freund’s adjuvant (CFA) administration did not modify escalation of home cage drinking in animals over four weeks, the relationship between drinking levels and hyperalgesia symptoms reversed between acute (1 week) and chronic (3–4 week) periods post-CFA administration, suggesting that either the motivational or analgesic effects of alcohol may be altered over the time course of chronic pain. We next examined ERK and GR phosphorylation in pain-related brain areas (including the central amygdala and prefrontal cortex subregions) in animals experiencing acute withdrawal from binge alcohol administration (2 g/kg, 6 h withdrawal) and CFA administration (four weeks) to model the neurobiological consequences of binge alcohol exposure in the context of pain. We observed a significant interaction between alcohol and pain state, whereby alcohol withdrawal increased ERK phosphorylation across all four frontocortical areas examined, although this effect was absent in animals experiencing chronic inflammatory pain. Alcohol withdrawal also increased GR phosphorylation across all four frontocortical areas, but these changes were not altered by CFA. Interestingly, we observed significant inter-brain regional correlations in GR phosphorylation between the insula and other regions investigated only in animals exposed to both alcohol and CFA, suggesting coordinated activity in insula circuitry and glucocorticoid signaling in this context. The results of these studies provide a greater understanding of the neurobiology of AUD and will contribute to the development of effective treatment strategies for comorbid AUD and pain.

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Behavioral and neural sensitivity to uncertain threat in individuals with alcohol use disorder: Associations with drinking behaviors and motives.

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