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Objective: Substance use initiation during early adolescence is associated with later development of substance use and mental health disorders. This study used various domains to predict substance use initiation, defined as trying any nonprescribed substance (e.g., alcohol, tobacco, cannabis), by age 12, using a large longitudinal data set., Methods: Substance-naive youths from the Adolescent Brain Cognitive Development Study (ages 9-10; N=6,829) were followed for 3 years. A total of 420 variables were examined as predictors of substance use initiation, using a penalized logistic regression with elastic net; domains spanned demographic characteristics, self and peer involvement with substance use, parenting behaviors, mental and physical health, culture and environment, hormones, neurocognitive functioning, and structural neuroimaging., Results: By age 12, 982 (14.4%) children reported substance initiation, with alcohol being the most common. Models with only self-report predictors had similar prediction performance to models adding hormones, neurocognitive factors, and neuroimaging predictors (AUC test =0.66). Sociodemographic factors were the most robust predictors, followed by cultural and environmental factors, physical health factors, and parenting behaviors. The top predictor was a religious preference of Mormon (coefficient=-0.87), followed by a religious preference for Jewish (coefficient=0.32), and by Black youths (coefficient=-0.32)., Conclusions: Sociodemographic variables were the most robust predictors of substance use initiation. Adding resource-intensive measures, including hormones, neurocognitive assessment, and structural neuroimaging, did not improve prediction of substance use initiation. The application of these large-scale findings in clinical settings could help to streamline and tailor prevention and early intervention efforts., Competing Interests: Dr. Gray has served as a consultant for Indivior and Jazz Pharmaceuticals and has received research support from Aelis Farma. The other authors report no financial relationships with commercial interests.

Objective: Moderate alcohol consumption is associated with decreased risk for depression, but it remains unclear whether this is a causal relationship or a methodological artifact. To compare the effects of consistent abstinence and occasional, moderate, and above-guideline alcohol consumption throughout early to middle adulthood on depression at age 50, the authors conducted a secondary analysis of the National Longitudinal Survey of Youth 1979 cohort and employed a marginal structural model (MSM) approach., Methods: Baseline was set at 1994, when individuals were ages 29-37. The MSM incorporated measurements of alcohol consumption in 1994, 2002, and 2006, baseline and time-varying covariates, and repeated measurements with the Center for Epidemiologic Studies Depression Scale-Short Form (CES-D-SF). A total of 5,667 eligible participants provided valid data at baseline, 3,593 of whom provided valid outcome data. The authors used all observed data to predict CES-D-SF means and rates of probable depression for hypothetical trajectories of consistent alcohol consumption., Results: The results approximated J-curve relationships. Specifically, both consistent occasional and consistent moderate drinkers were predicted to have reduced CES-D-SF scores and rates of probable depression at age 50 compared with consistent abstainers (CES-D-SF scores: b=-0.84, 95% CI=-1.47, -0.11; probable depression: odds ratio=0.58, 95% CI=0.36, 0.88 for consistent occasional drinkers vs. abstainers; CES-D-SF scores: b=-1.08, 95% CI=-1.88, -0.20; probable depression: odds ratio=0.59, 95% CI=0.26, 1.13 for consistent moderate drinkers vs. consistent abstainers). Consistent above-guideline drinkers were predicted to have slightly increased risk compared with consistent abstainers, but this was not significant. In sex-stratified analyses, results were similar for females and males., Conclusions: This study contributes preliminary evidence that associations between moderate alcohol consumption and reduced risk for depression may reflect genuine causal effects. Further research using diverse methodologies that promote causal inference is required.

Objective: Data on the neurodevelopmental and associated behavioral effects of light to moderate in utero alcohol exposure are limited. This retrospective investigation tested for associations between reported maternal prenatal alcohol use and psychological, behavioral, and neurodevelopmental outcomes in substance-naive youths., Methods: Participants were 9,719 youths (ages 9.0 to 10.9 years) from the Adolescent Brain Cognitive Development Study. Based on parental reports, 2,518 (25.9%) had been exposed to alcohol in utero. Generalized additive mixed models and multilevel cross-sectional and longitudinal mediation models were used to test whether prenatal alcohol exposure was associated with psychological, behavioral, and cognitive outcomes, and whether differences in brain structure and resting-state functional connectivity partially explained these associations at baseline and 1-year follow-up, after controlling for possible confounding factors., Results: Prenatal alcohol exposure of any severity was associated with greater psychopathology, attention deficits, and impulsiveness, with some effects showing a dose-dependent response. Children with prenatal alcohol exposure, compared with those without, displayed greater cerebral and regional volume and greater regional surface area. Resting-state functional connectivity was largely unaltered in children with in utero exposure. Some of the psychological and behavioral outcomes at baseline and at the 1-year follow-up were partially explained by differences in brain structure among youths who had been exposed to alcohol in utero., Conclusions: Any alcohol use during pregnancy is associated with subtle yet significant psychological and behavioral effects in children. Women should continue to be advised to abstain from alcohol consumption from conception throughout pregnancy.