Identifying a multivariate endophenotype for substance use disorders using psychophysiological measures.

This investigation examined how reduced amplitude of the P300 event-related potential (elicited from a visual oddball task) can be used together with an electrodermal response modulation measure (indexing the ability to inhibit responsivity to a temporally predictable aversive stimulus) to identify adolescents at especially high risk to develop substance dependence. One hundred and twenty-nine 17-year-old boys were divided into groups characterized as low risk (high amplitude P300 and good electrodermal modulation), high risk (reduced amplitude P300 and poor modulation), or intermediate risk (a high or good score on one measure and a low or poor score on the other). P300 amplitude and electrodermal modulation were uncorrelated. High-risk boys had 4-6 times more alcohol dependence than intermediate or low-risk boys and 2-3 times more nicotine dependence. Performance on an antisaccade eye-tracking task in which participants directed their gaze in a direction opposite to target movement was related to electrodermal modulation but not P300 amplitude. The results from all three psychophysiological measures together suggest that the neural circuits affecting P300 amplitude and electrodermal response modulation are different and that poor electrodermal response modulation may reflect an inhibitory control deficit mediated by the frontal lobes.