Chunk #122 — 5. Implications for understanding gene-brain-behavior relationships in health and disease — 5.2. An example: P3 as intermediate phenotype for externalizing disorders
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 evidence that P3 amplitude reduction is a genetically transmitted marker of risk, rather than consequence of drinking. Interestingly, animal models show a pattern of ERP differences that parallels the human findings described above: selectively bred alcohol-preferring rats show reduced P3 amplitude in the parietal cortex and increased fast-frequency EEG activity compared with and non-preferring rats(Criado and Ehlers, 2010). Thus, high heritability of P3 (and associated event-related theta oscillations) in the general population, its robust familial association with alcoholism, genetic correlations with a broader externalizing trait, and little modification by alcohol use, makes it a good intermediate phenotype (endophenotype) for genetically transmitted vulnerability to alcoholism.
