It is not known whether phase-locking differences between externalizing- and control-groups reflected preexisting differences between the groups (e.g., genes) or neurotoxic effects of chronic/heavy substance use. Indeed, significant effects and better model-fit values were associated with phase-locking for SUDs. Substance use, particularly alcoholism, has been posited to interfere with GABAergic and glutamatergic neurotransmission, which may be in part responsible for some phase-locking difference reported here. However, P3 deficits in SUDs appear to be strongly familial (Euser et al., 2012) and mouse strains liable to develop an alcohol preference show phase-locking deficits before ever being administered alcohol (Criado and Ehlers, 2009). Given extant literature, we do not conclude that phase-locking effects are a consequence of substance use, although future research should examine this notion more fully. We do conclude that phase-locking may contribute to the P3 amplitude differences between heavy substance users and controls. Although there is no widely-accepted method to determine the significance of changes in QICu values, adding phase-locking measures clearly better-accounted for externalizing prediction because QICu values were smaller when phase-locking was used as a predictor of SUDs
