Objective. Externalizing psychopathology (EXT) is a psychiatric construct implicated in the etiology and comorbidity of various disinhibited and impulsive behaviors. P300 amplitude, an index of neural processing of salient or unexpected stimuli measured with the event-related potential technique, has been shown to be reduced among adolescents at risk for EXT. This dissertation is comprised of a series of studies that aim to advance understanding of the EXT-P300 amplitude reduction (P3AR) association using from a longitudinal and comprehensive study of adolescent monozygotic twins. P3AR was elicited by target stimuli and novelty stimuli, and measured using the conventional peak-in-window (Peak-P3) approach and temporal-spatial principal components analysis (TSPCA) approach. The first study described the measurement characteristics of P3AR, including reliability, gender differences, and 1-year longitudinal change. The second study examined the association between EXT liability, a composite index derived from diagnostic-symptom indicators, and P3AR. The third study examined the influence of manifest substance use on the expression of P3AR. Method. Forty-eight monozygotic twin pairs (ages = 14--16 year-old; 24 female pairs) completed a multi-domain assessment of electrophysiology, substance use history, and psychopathological history and returned to complete the assessment again one year later. Electroencephalogram (EEG) was recorded using a 64-sensor net while participants engaged in a three-stimulus visual oddball paradigm designed to elicit separate kinds of P3AR. Infrequent non-target pictures served as novelty stimuli to elicit the anterior-central P3a amplitude, or Novelty P3 amplitude. Infrequent head-like ovals served as target stimuli to elicit the posterior P3b amplitude, or Target P3 amplitude. Peak-P3 was calculated for three midline electrodes that have been the focus of prior P3-EXT studies (FZ, CZ, and PZ). TSPCA was used to identify and extract prominent and coherent patterns of neuroeletric activity underlying Peak-P3. Results. In study 1, all Peak-P3 phenotypes and the vast majority of TSPCs demonstrated strong intra-individual reliability and cross-twin correlations. In addition, many P300 amplitude phenotypes demonstrated change as a function of age. In study 2, Novelty Peak-P3 recorded at the PZ electrode correlated moderately with EXT liability for males but not females. The same pattern of effect was present for Target Peak-P3 recorded at the FZ electrode but the effect was not statistically significant. TSPCs underlying Novelty Peak-P3 (e.g., Novelty 449ms SC1 and Novelty 449ms SC5) were found to index separate aspects of EXT liability. Novelty 449ms SC1 overlapped much with Target 488ms SC1 as a correlate of EXT liability, consistent with the notion that they represent a certain aspect of P3AR elicited by both novelty stimuli and target stimuli that is associated EXT liability. In study 3, we evidence that suggested that Novelty 449ms SC5 and Target 488ms SC5 might be affected by the consequences of adolescent substance use. In contrast, Novelty 449ms SC1 and Target 488ms SC1 seemed unaffected by adolescent substance use, supporting the alternative hypothesis that these TSPCs correlated with EXT liability due to inherited factors. Conclusions. The psychometric properties of adolescent Peak-P3 recorded at FZ, CZ, and PZ electrodes, and most TSPCs, were strong, which fulfills an important requirement for a clinically useful tool to assess EXT liability. Consistent with prior studies, P3AR may be a correlate of EXT liability for males more so than females. TSPCs may have utility to parse P300 amplitude into phenotypes that correlate with EXT liability (Novelty 449ms SC1 and Target 488ms SC1), or that index changes in brain function corresponding to adolescent substance use (Novelty 449ms SC5 and Target 488ms SC5). However, because TSPC has not been applied to the study of EXT liability before, more research with TSPC-derived phenotypes is needed in order to replicate these new findings, and to identify the aspects of brain function that these phenotypes represent.
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