Chunk #120 — 5. Implications for understanding gene-brain-behavior relationships in health and disease — 5.2. An example: P3 as intermediate phenotype for externalizing disorders
Numerous studies have shown that oddball P3 amplitude is reduced in alcoholics and, most importantly, in unaffected biological relatives of alcoholics(Begleiter and Porjesz, 1990; Hill et al., 1995; Hill et al., 1988; Iacono et al., 2003, 2008; Polich et al., 1994; Porjesz and Begleiter, 1991); this evidence summarized in a recent meta-analysis (Euser et al., 2012). The robust finding of familial association between P3 and alcoholism is corroborated by the evidence for high heritability of individual differences in P3 amplitude in the general population(Anokhin et al., 2001; Katsanis et al., 1997; van Beijsterveldt et al., 1998b; van Beijsterveldt and van Baal, 2002). Furthermore, reduced P3 was found to be associated not only with AUDs but also with nicotine dependence (Anokhin et al., 2000), drug dependence (Bauer, 1997), conduct disorder (Bauer and Hesselbrock, 1999), suggesting that diminished P3 indicates an inherited predisposition for a spectrum of addictive behaviors and comorbid externalizing psychopathology (Gilmore et al., 2010; Iacono et al., 2003). Multivariate genetic analyses of twin data demonstrated significant genetic correlations between P3 and latent externalizing factor, thus supporting the notion that
