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Background Low levels of alcohol responses (low LRs) are genetically influenced phenotypes that are identified before alcohol dependence and predict future heavy drinking and alcohol problems. A recent paper described 13 LR-related blood oxygen level-dependent ( BOLD) response contrast patterns observed during an emotional face recognition task that might reflect cognitive processes contributing to LR and that might themselves predict adverse alcohol outcomes ( Paulus et al., Biol Psychiatry 2012; 72: 848). This paper evaluates the predictive implications of those functional magnetic resonance imaging (f MRI) patterns. Methods Of 120 subjects from Paulus and colleagues (2012), 114 (57 low and high LRs; ~50% females) were interviewed 5 years later at age 25. Correlations between baseline f MRI patterns and alcohol-related outcomes were evaluated, and regression analyses were used to determine if BOLD response contrasts incremented over LR in predicting outcomes. Results Baseline f MRI patterns in 5 of 13 baseline regions of interest correlated with adverse outcomes. Such patterns in insular regions, particularly the left anterior insula, and the right frontal gyrus, added to LR in predicting alcohol problems. The relationships remained robust when exact binomial procedures were used, but, reflecting the small sample size, it was not possible to adequately consider Bonferroni corrections. Conclusions The data suggest that f MRI BOLD response contrasts predicted heavier drinking and alcohol problems 5 years later, even after considering baseline low LRs. Future work will focus on whether f MRI results can predict outcomes in larger samples and among young nondrinkers, as well as how the imaging results increase understanding of the processes through which LR operates. [ABSTRACT FROM AUTHOR]

Background: A low level of response (i.e., a low LR) to alcohol is a genetically influenced phenotype that predicts later alcoholism. While the low LR reflects, at least in part, a low brain response to alcohol, the physiological underpinnings of the low LR have only recently been addressed. Methods: Forty-nine drinking but not yet alcoholic matched pairs of 18- to 25-year-old subjects ( N = 98; 53% women) with low and high LRs as established in separate alcohol challenges were evaluated in 2 event-related functional magnetic resonance imaging (fMRI) sessions (placebo and approximately 0.7 ml/kg of alcohol) while performing a validated stop signal task. The high and low LR groups had identical blood alcohol levels during the alcohol session. Results: Significant high versus low LR group and LR group × condition effects were observed in blood oxygen level-dependent (BOLD) signal during error and inhibitory processing, despite similar LR group performance on the task. In most clusters with significant (corrected p < 0.05, clusters > 1,344 μl) LR group × alcohol/placebo condition interactions, the low LR group demonstrated relatively less, whereas the high LR group demonstrated more, error and inhibition-related activation after alcohol compared with placebo. Conclusions: This is one of the first fMRI studies to demonstrate significant differences between healthy groups with different risks of a future life-threatening disorder. The results may suggest a brain mechanism that contributes to how a low LR might enhance the risk of future heavy drinking and alcohol dependence. [ABSTRACT FROM AUTHOR]