The model proposed here encompasses potential neural systems underlying the risk for AUD and serves as a framework for understanding the complex traits associated with alcoholism risk. The nature of the inborn variations in brain structure and function associated with risk for AUD and other comorbid conditions requires further study. At present, it appears that premorbid dysfunction of the cerebellothalocortical system may predispose an individual to an externalizing pathway to AUD that is prompted by difficulties with behavioral control and inhibition. Following the reinforcing pleasurable effects of alcohol exposure, behavioral under control may lead to an inability to restrain future consumption. Alternatively, abnormalities in the extended limbic network, including the orbitofrontal cortex, amygdala, and hypothalamus may drive the negative affective characteristics shown to elicit alcohol abuse, thereby making the anxiolytic properties of ethanol more gratifying. Complementary, failure to regulate the HPA axis may influence an individual's behavioral response to novelty and anxiety-related behaviors in the presence of stress, motivating the use of alcohol to achieve sedation.
