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Early substance use initiation (SUI) places youth at substantially higher risk for later substance use disorders. Furthermore, adolescence is a critical period for the maturation of brain networks, the pace and magnitude of which are susceptible to environmental influences and may shape risk for SUI.

Objective: The purpose of the study was to determine the effects of cigarette smoking on brain regional function in a group of chronic smokers by using cerebral blood flow (CBF) measures and positron emission tomography (PET). Method: Nineteen tobacco smokers were studied after about 12 hours of smoking abstinence. Regional CBF (rCBF) measures were obtained with PET and [[sup.15]O] [H.sup.2]O in six consecutive scans. Two average-nicotine-yield (1.0 mg) and one denicotinized (0.08 mg) research cigarettes with similar tar yields (9.5 mg and 9.1 mg, respectively) were smoked in a double-blind design, preceded and followed by baseline scans. The rCBF effects of smoking were compared to baseline measures and between cigarettes, as well as to subjective ratings of craving for cigarettes. Results: Smoking the first cigarette of the day resulted in increases in rCBF in the visual cortex and the cerebellum and reductions in the anterior cingulate, the right hippocampus, and the ventral striatum, including the nucleus accumbens. Cigarette craving scores correlated with rCBF changes in the dorsal anterior cingulate and right hippocampus. Less pronounced effects were observed with the second cigarette and the denicotinized cigarette. Conclusions: Smoking affects rCBF not only in areas of the brain rich in nicotinic cholinergic receptors but also in areas implicated in the rewarding effects of drugs of abuse. Furthermore, craving for a cigarette in chronic smokers was correlated with rCBF in the right hippocampus, an area involved in associating environmental cues with drugs, and in the left dorsal anterior cingulate, an area implicated in drug craving and relapse to drug-seeking behavior.

Abnormalities in responses to reward and loss are implicated in the etiology of antisocial behavior and psychopathic traits. Although there is evidence for sex differences in neural response to reward and loss, it remains unclear how sex differences may moderate links between these neural responses and the phenotypic expression of antisocial behavior and psychopathic traits. This study examined sex differences in associations of neural response to reward and loss with antisocial personality symptoms and psychopathic traits. Functional neuroimaging data were collected during a monetary incentive delay task from 158 participants. Among males, during loss anticipation, activation in the left nucleus accumbens was negatively associated with antisocial behavior. Among females, during loss feedback, activation in the left nucleus accumbens and left amygdala was negatively associated with antisocial behavior. These results suggest that phenotypic sex differences in psychopathic traits and antisocial behavior may in part be attributable to different etiological pathways.

Graphical Abstract

•Sex differences exist in underlying risk factors for substance use disorder.•Sex differences in brain development may underlie these divergent risk pathways.•Interpretation of sex differences depends on study methods.•Future research on mechanisms underlying sex differences is needed.

•The ABCD Substance Use Workgroup describes substance use patterns within the cohort.•The ABCD cohort is entering adolescence and initiating substance use.•By ages 12–13, nearly 40% report lifetime substance experimentation and/or use.•Nearly 7.5% also reported lifetime substance use (>experimentation).•Sociodemographic and parental substance problems remain as predictors of initiation.

Background: Children of alcoholics (COAs) are at elevated risk for alcohol use disorders (AUD), yet not all COAs will develop AUD. The 2 primary aims of this study were to identify neural activation mechanisms that may mark protection or vulnerability to AUD in COAs and to map the same activation patterns in relation to risk behavior (externalizing or internalizing behavior).

•Sociodemographic variability was observed in substance use cognitions/perceptions•Cognitions/perceptions of substances often differ by substance type•Individual-, peer-, and parent-level factors are associated with curiosity to use alcohol and nicotine