One variant of substance-use disorder is characterized by behavioral disinhibition. In this report, we martial evidence for a model for the development of this variant. We hypothesize that genetic liability for this variant is reflected in a spectrum of risk indicators linked to the inability or unwillingness to inhibit behavioral impulses. Included in this spectrum are personality traits suggesting low constraint, and externalizing psychopathology, including conduct, oppositional defiant, and attention-deficit disorder in children and antisocial personality disorder and behavior in adults. We further hypothesize that these individual differences in behavioral disinhibition are manifestations of underlying central nervous system processes associated with various psychophysiological anomalies, some of which may index genetic risk for substance abuse. Support for the model is derived from the analysis of findings from the Minnesota Twin Family Study, an epidemiological investigation of approximately 2,700 adolescent twins and their parents.

To determine if the P300 component of the event-related potential indexes risk for substance use and related disorders, we presented a community sample of 377 16–18-year-old males a visual oddball task and selected 31 subjects with the smallest and 31 subjects with the largest P300 amplitudes. An additional 31 subjects whose amplitudes fell in the middle of the amplitude distribution were assigned to the average group. The small and average amplitude groups were more likely to have alcohol dependence and more symptoms of alcohol dependence than the large amplitude subjects. The small amplitude group had more symptoms of illicit drug dependence than the other groups. There was also a significantly larger proportion of subjects with externalizing disorders in the small amplitude group than in the large P300 group. These findings suggest that P300 amplitude may index a spectrum of risk for disinhibited psychopathology.

To determine if the inability to take advantage of the predictability of an aversive stimulus to diminish its psychological impact reflects a deficit in inhibitory control related to the development of substance dependence, we recorded skin conductance responses (SCRs), heart rate (HR), and anticipatory electrodermal nonspecific fluctuations (NSFs) from 175 16–18-year-old boys when a white noise blast was either unpredictable or temporally predictable. Compared with boys who had moderately reduced or augmented SCRs to predictable blasts (moderate and poor modulators, respectively), boys whose SCRs were greatly reduced (good modulators) had fewer symptoms of alcohol and nicotine dependence and more anticipatory NSFs. HR appeared to index an active coping response for good and moderate modulators. The autonomic response pattern evident for good modulators may index an inhibitory control mechanism protecting them from developing substance dependence.