The genetics of alcoholism, impulsive behavior and neurodegeneration may overlap. Proinflammatory genes appear to be involved in alcoholic neurodegeneration and the genetics of alcoholism. Human alcoholic brain shows increased NF-κB gene transcription (Okvist et al., 2007), a key proinflammatory transcription factor. Similarly human alcoholic brain shows increased proinflammatory cytokine and microglial protein expression (He and Crews, 2008). Animal studies find alcohol induced proinflammatory gene expression with neurodegeneration (Crews et al., 2006a; Qin et al., 2008). Human genetic variations in NF-κB genes have been associated with increased risk for human alcoholism, particularly early onset alcoholism (Edenberg et al., 2008). Proinflammatory cytokines found in alcoholic human brain (He and Crews, 2008) increase the reward value of alcohol drinking in mice (Blednov et al., 2005). Animal models of genetic high risk for alcoholism, e.g. the “P-alcohol preferring rat” that was bred for heavy alcohol drinking, have increased risk for alcoholic brain damage corresponding with increased genetic risk for alcoholism (Crews and Braun, 2003). High impulsivity has also been found in families with alcoholism, suggestive of a genetic link (Saunders et al., 2008). Thus, the genetics of impulsivity overlaps with genetic risks for alcohol use disorder and possibly alcoholic neurodegeneration.
