Gray matter volume abnormalities and externalizing symptoms in subjects at high risk for alcohol dependence.

Reduced right amygdala volumes have been reported in young, alcohol-naïve subjects at high risk (HR) for alcohol dependence. The differences in brain morphometry have been associated with an excess of externalizing behaviors in these subjects. This may reflect a neurobiological vulnerability to alcohol dependence. Existing Magnetic Resonance Imaging (MRI) studies on these subjects have examined only a few, pre-selected brain regions using the manual regions of interest (ROI) approach. MRI of HR subjects (n = 20) and age, sex, and handedness-matched low-risk (LR) subjects (n = 21) were analyzed using optimized voxel-based morphometry and ROI approach. The externalizing symptoms of these subjects and their fathers were measured using the Semi-Structured Assessment for the Genetics of Alcoholism. HR subjects had significantly smaller volumes of superior frontal, cingulate and parahippocampal gyri, amygdala, thalamus and cerebellum. These gray matter volumes correlated negatively with externalizing symptoms scores. Subjects at HR for alcoholism have reduced volumes of critical areas of brain gray matter, which are associated with increased externalizing symptoms. These represent key endophenotypes of alcoholism.