[Cognitive vulnerability to alcohol dependence: related neuroanatomic endophenotypes]

Executive function impairments and high level of impulsivity may constitute heritable endophenotypes that confer predisposition for alcohol dependence. Brain volume abnormalities have also been reported in young, alcohol-naïve subjects at high risk (HR) for alcohol dependence, and linked to cognitive dysfunction.

This paper presents a literature review of magnetic resonance imaging (MRI) studies that examined brain volumes in adolescent/young adult HR offspring from families with multiple cases of alcohol dependence compared to low risk controls with no family history of alcohol or drug misuse. In some of these studies, executive functioning and externalizing symptoms were also assessed.

In HR subjects, local white matter volume deficits were found in the corpus callosum and in the right orbito-frontal cortex, and lower fractional anisotropy in the left inferior longitudinal fasciculus and in the right optic radiation. Altered fronto-cerebellar connectivity has also been reported. Diminished gray matter volume of the cerebellar cortex was found in HR subjects, in the frontal, cyngulate and para-hippocampal gyri, and also in the amygdala, the thalamus and the cerebellum. These structural abnormalities have been associated with higher impulsivity level and executive function impairments, themselves markers of vulnerability to alcoholism. These premorbid cerebral abnormalities may increase the risk for developing an alcohol use disorder in HR subjects through atypical control processing.

Brain abnormalities may potentially constitute an abnormal neural network that might underlie the risk towards alcohol dependence. These circuitry abnormalities might contribute to the reward deficiency, as well as impaired response inhibition that predict impulsive spectrum behavior, which are thought to represent the inherited vulnerability to alcohol dependence in HR individuals.