Chunk #121 — 5. Implications for understanding gene-brain-behavior relationships in health and disease — 5.2. An example: P3 as intermediate phenotype for externalizing disorders
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 P3 indicates genetic diathesis for externalizing disorders (Hicks et al., 2007). Importantly, a converging line of evidence suggests that reduced P3 indicates a genetically transmitted deficit predating alcohol use and abuse, rather than a consequence of heavy drinking: the reduction of P3 is present in high-risk (i.e. family history positive) adolescents was present before the onset of drinking (Hill and Shen, 2002; Hill et al., 1999; Hill et al., 2000); P3 is not significantly affected by alcohol use (Perlman et al., 2009); in longitudinal studies reduced P3 prospectively predicted the onset of alcohol abuse(Gilmore et al., 2012) as well as aggression and crime (Gao and Raine, 2009); in non-alcohol dependent social drinkers without family history of alcoholism P3 amplitude was unrelated to lifetime alcohol intake(Bijl et al., 2005); finally, a co-twin control study(Carlson et al., 2002) has shown that in twin pairs discordant for AUDs the alcohol abusing/dependent twins' amplitude did not differ from that of non-alcoholic co-twins, providing further
