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Limbic responses to reward cues correlate with antisocial trait density in heavy drinkers.

ABSTRACT: Antisocial traits are common among alcoholics- particularly in certain subtypes. Although people with antisocial tendencies show atypical brain activation in some emotion and reward paradigms, how the brain reward systems of heavy drinkers (HD) are influenced by antisocial traits remains unclear. We used subjects' preferred alcohol drink odors (AO), appetitive (ApCO) and non-appetitive (NApO) control odors in functional magnetic resonance imaging (fMRI) to determine if reward system responses varied as a function of antisocial trait density (ASD). In this retrospective analysis, we examined 30 HD who had participated in imaging twice: once while exposed to clamped intravenous alcohol infusion targeted to 50mg%, and once during placebo saline infusion. Under placebo, there were positive correlations between ASD and blood oxygenation level dependent (BOLD) activation in the [AO>ApCO] contrast in the left dorsal putamen, while negative correlations were present in medial orbitofrontal cortex (OFC) and the bilateral amygdala. A similar pattern was observed in the correlation with the [AO>NApO] contrast. This inverse relationship between ASD and activation in OFC and amygdala was specific to AO. However, negative correlations between ASD and the [ApCO>NApO] contrast were also present in the insula, putamen, and medial frontal cortex. These data suggest that frontal and limbic reward circuits of those with significant ASD are less responsive to reward cues in general, and particularly to alcohol cues in medial OFC and amygdala. These findings are broadly consistent with the reward deficiency syndrome hypothesis, although positive correlation in the striatum suggests regional variability.

SUBMITTER: Oberlin BG

PROVIDER: S-EPMC3288676 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Limbic responses to reward cues correlate with antisocial trait density in heavy drinkers.

Oberlin Brandon G BG Dzemidzic Mario M Bragulat Veronique V Lehigh Cari A CA Talavage Thomas T O'Connor Sean J SJ Kareken David A DA

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Antisocial traits are common among alcoholics- particularly in certain subtypes. Although people with antisocial tendencies show atypical brain activation in some emotion and reward paradigms, how the brain reward systems of heavy drinkers (HD) are influenced by antisocial traits remains unclear. We used subjects' preferred alcohol drink odors (AO), appetitive (ApCO) and non-appetitive (NApO) control odors in functional magnetic resonance imaging (fMRI) to determine if reward system responses va ...[more]

PMID: 22227139

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Project description:Background: Alcohol-associated liver disease (ALD) is the most common disorder of prolonged drinking. Mechanisms underlying cirrhosis in such patients remain unclear. MicroRNAs play regulatory role in several diseases, are affected by alcohol and may be important players in alcohol use disorders, such as cirrhosis. Methods: We investigated serum samples from heavy chronic alcohol users (80 g/day (male) and 50 g/day (female) for ≥10 years) that were available from our previously reported GenomALC study. A subset of GenomALC drinkers with liver cirrhosis (cases, n = 24) and those without significant liver disease (drinking controls, n = 23) were included. Global microRNA profiling was performed using high-throughput real-time quantitative PCR to identify the microRNA signatures associated with cirrhosis. Ingenuity Pathway Analysis (IPA) software was utilized to identify target mRNAs of significantly altered microRNAs, and molecular pathways were analysed. Identified microRNAs were analysed for correlation with traditional liver disease biomarkers and risk gene variants previously reported from GenomALC genome-wide association study. Results: The expression of 21 microRNAs was significantly downregulated in cases compared to drinking controls (p < 0.05, ∆∆Ct > 1.5-fold). Seven microRNAs (miR-16, miR-19a, miR-27a, miR-29b, miR-101, miR-130a, and miR-191) had a highly significant correlation (p < 0.001) with INR, bilirubin and MELD score. Three microRNAs (miR-27a, miR-130a and miR-191) significantly predicted cases with AUC-ROC 0.8, 0.78 and 0.85, respectively (p < 0.020); however, INR performed best (0.97, p < 0.001). A different set of six microRNAs (miR-19a, miR-26a, miR-101, miR-151-3p, miR-221, and miR-301) showed positive correlation (ranging from 0.32 to 0.51, p < 0.05) with rs10433937:HSD17B13 gene variant, associated with the risk of cirrhosis. IPA analysis revealed mRNA targets of the significantly altered microRNAs associated with cell death/necrosis, fibrosis and increased steatosis, particularly triglyceride metabolism. Conclusions: MicroRNA signatures in drinkers distinguished those with liver cirrhosis from drinkers without liver disease. We identified mRNA targets in liver functions that were enriched for disease pathogenesis pathways.

Dataset Information

Limbic responses to reward cues correlate with antisocial trait density in heavy drinkers.

Publications

Limbic responses to reward cues correlate with antisocial trait density in heavy drinkers.

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