Reduced frontal lobe activity in subjects with high impulsivity and alcoholism

Objective: Impulsivity is an important characteristic of many psychiatric disorders, including substance-related disorders. These disinhibitory disorders have a similar underlying genetic diathesis, with each disorder representing a different expression of the same underlying genetic liability. This study assessed whether there is a relationship between impulsivity and alcohol dependence, and their correlations with P3 (P300) amplitude, a proposed endophenotype of alcoholism. Methods: Healthy control subjects (n = 58) and subjects with DSM-IV diagnosis of alcohol dependence (n = 57) were assessed with a visual oddball task. Event-Related Potentials (ERPs) were recorded from 61 scalp electrodes and P3 amplitudes measured. Barratt Impulsiveness Scale (BIS), version 11, was used to evaluate impulsivity. Source localization of P3 was computed using low-resolution brain electromagnetic tomography (LORETA). Results: Alcoholic subjects manifested reductions in target P3 amplitudes (p < 0.0001). Using LORETA, significantly reduced activation was mapped in the cingulate, medial, and superior frontal regions in alcoholic subjects and highly impulsive subjects. Alcoholic subjects had significantly higher scores on the BIS (p < 0.0001) than nonalcoholic individuals. There were significant negative correlations between total scores on BIS and P3 amplitude (r = -0.274, p = -0.003, on Pz; r = -0.250, p = 0.007, on Cz). Conclusions: Our results demonstrate a strong frontal focus of reduced activation during processing of visual targets in alcoholic subjects and individuals with higher impulsivity. The findings suggest that impulsivity may be an important factor that underlies the pathogenesis of alcohol dependence. Studies are underway to examine the relationship between impulsivity and ERPs in offspring of alcoholic subjects, and to identify genes associated with the underlying predisposition involved in disinhibitory disorders.