In our effort to understand the genetic liability to AD, research has focused on characterizing individual differences in the biological systems that regulate the breakdown of alcohol and the neuronal systems/pathways that are believed to be affected by alcohol. Research on the metabolism of alcohol suggests the involvement of several enzymes. The oxidative pathway involves aldehyde dehydrogenase (ALDH), alcohol dehydrogenase (ADH), cytochrome P450 2E1, and catalase. The non-oxidative pathway involves fatty acid ethyl ester and phospholipidase D. Differences in the functionality of the ALDH and ADH enzymes have been linked to, (1) increased risk for alcohol-induced tissue damage (cirrhosis; Chao et al., 1994), and (2) protection against developing AD (Chen et al., 2009). In the context of brain effects, the acute and chronic effects of alcohol exposure are very important, as the cycle of addiction is dependent upon how an individual responds to repeated alcohol use over time. Based on the body of literature across humans and animals, AD is likely to involve neuronal circuits involved in the Binge/Intoxication, Withdrawal/Negative Affect, and Preoccupation/Anticipation stages of the addiction cycle (Koob and
