Henri Begleiter

P300 event-related potential amplitude as an endophenotype of alcoholism--evidence from the collaborative study on the genetics of alcoholism.

There is substantial information supporting the role of genetic factors in the susceptibility for alcohol dependence. However, the identification of specific genes that contribute to this predisposition has proven elusive, although several theoretically relevant candidates, e.g. DRD2 or 5-HT(1B), have been considered. The difficulty in identifying specific genes may be related to the clinical heterogeneity of the disorder resulting in a poorly defined phenotype for genetic analysis. An alternative approach to the use of a diagnostic phenotype for identifying alcoholism susceptibility genes may lie in the examination of the neurobiological correlates of the disorder, the so-called endophenotypes. One possible endophenotype of alcohol dependence may be related to the P300 waveform of the event-related brain potential (ERP). Using data obtained from the Collaborative Study on the Genetics of Alcoholism (COGA), a multi-site family-based study, the utility of P300 amplitude as an endophentype was examined. Differences in P300 amplitude were found between alcoholics and nonalcoholics, between unaffected relatives of alcoholics and relatives of controls, as well as between unaffected offspring of alcoholic fathers and offspring of controls. A genetic analysis indicated that attributes of the P(3) ERP waveform are heritable, and a quantitative trait locus analysis found linkage to several chromosomal regions. These data provide significant support for P300 as an endophenotype for alcohol dependence.

Temporal recovery of auditory evoked potentials in individuals at risk for alcoholism

The present investigation examined auditory evoked potential (AEP) recovery functions in both high-risk (HR, N = 23, mean = 22.3) and low-risk (LR, N = 27, mean = 23.0) males. A series of binaural auditory stimuli, with randomly interposed interstimulus intervals (ISIs) of 0.5, 1.0, and 10.0 s, were used to elicit the N1 and P2 components of the AEP. Scalp potentials were recorded from the 19 electrodes comprising the 10/20 International System. For purposes of statistical analysis, five electrode groups were created: frontal (F), central (C), parietal (P), occipital (O), and temporal (T). The results of within-group MANOVA demonstrated that in both LR and HR individuals, increases in the ISI produced significant N1 and P2 amplitude increases without significant latency differences. These amplitude increases occurred primarily in the F and C regions. However, the results of between-group MANOVA indicated that there were no differences in the recovery functions of the two risk groups. Our results indicate that in both LR and HR individuals, recovery functions are responsive to changes in increasing ISI. However, they did not effectively discriminate between risk groups. It is speculated that risk group differences may be apparent with the use of an ethanol challenge.