P300 amplitude as an indicator of externalizing in adolescent males

Abstract

Reduced P300 amplitude is reliably found in individuals with a personal or family history of alcohol problems. However, alcoholism is part of a broader externalizing spectrum that includes other substance use and antisocial disorders. We hypothesized that reduced P300 is an indicator of the common factor that underlies disorders within this spectrum. Community males (N=969) were assessed at age 17 in a visual oddball task. Externalizing was defined as the common factor underlying symptoms of alcohol dependence, drug dependence, nicotine dependence, conduct disorder, and adult antisocial behavior. A robust association was found between reduced P300 amplitude and the externalizing factor, and this relation accounted for links between specific externalizing disorders and P300. Our findings indicate that reduced P300 amplitude is an indicator of the broad neurobiological vulnerability that underlies disorders within the externalizing spectrum.

Figures

Figure 1

Schematic depiction of stimuli used in the rotated-heads visual oddball task. Nontargets (bottom) occurred on 160 trials and required no response. Each of the four target stimuli was presented on 20 trials; for these stimuli, the participant pressed a button with either the left or right hand to indicate the side of the head on which the ear was positioned. For easy head targets (top), the nose was pointed up and thus the correct button response (“left” or “right”) corresponded directly to the side of the screen on which the ear appeared. For hard targets (middle), the nose was pointed down and thus the correct button response was opposite to the side of the screen on which the ear appeared.

Figure 2

Average ERP waveforms for participants in the lowest quartile of the distribution of scores on the externalizing (EXT) factor, and for individuals who scored (a) above the median of the distribution, (b) in the highest quartile of the distribution, and (c) in the highest decile (10%) of the distribution. The externalizing factor is defined as the first principal component derived from a PCA of DSM-III-R symptoms of alcohol dependence, drug dependence, nicotine dependence, conduct disorder, and adult antisocial behavior. A score on this factor was computed for each individual participant using the regression method.

Figure 3

Scatterplot of the association between mean P300 amplitude and continuous scores on the externalizing factor across all study participants (N=969); solid line is best-fitting regression line. A standard geometric transformation, using the rotation matrix Rθ=(cosθ−sinθsinθcosθ), where θ represents the desired rotation angle, was applied to the raw factor score data in order to vertically align low scores on externalizing; the data were normalized to unit-length axes prior to rotation and rescaled to the original units afterward. For purposes of plotting, the minimum score on the externalizing factor was subtracted from each resultant value, such that 0 now represents the minimum score, rather than the mean.