Background: Adolescence is a critical developmental stage for the emergence of major depressive disorder (MDD). Structural and diffusion neuroimaging studies have highlighted the anterior cingulate cortex (ACC) as a key region implicated in emotion regulation, stress reactivity, and mood processing. However, few studies have examined whether microstructural characteristics of the ACC, reflected by mean diffusivity (MD) within gray matter–white matter (GM–WM) contrast regions, are associated with depression in early adolescence. Objective: To examine whether mean diffusivity (MD) within the GM–WM contrast of the left caudal anterior cingulate cortex (ACC) is associated with a past diagnosis of MDD among adolescents in the Adolescent Brain Cognitive Development (ABCD) Study, after accounting for demographic, socioeconomic, and adversity-related factors. Methods: Data were drawn from adolescents with diffusion MRI–derived mean diffusivity measures and diagnostics. The independent variable was mean diffusivity (MD) of the GM–WM contrast in the left caudal ACC. The primary outcome was past MDD diagnosis based on structured psychiatric assessments. Covariates included age, sex, socioeconomic status (SES), and exposure to adverse childhood experiences (ACEs). Logistic regression models tested the association between ACC MD and past MDD. A secondary model evaluated the relationship between ACC MD and past suicide attempt. Results: Mean diffusivity of the left caudal ACC was associated with the odds of past MDD, independent of age, sex, SES, and adversity exposure. In contrast, ACC mean diffusivity was not associated with a history of suicide attempt. Conclusions: Increased mean diffusivity in the caudal ACC may indicate microstructural alterations associated with depressive vulnerability in adolescence. ACC tissue integrity may serve as a sensitive neural correlate of early-onset depression.

Background: Sexual and gender minority (SGM) youth are at elevated risk for adverse mental health and substance use outcomes. Stressors such as family conflict, discrimination, and trauma have been suggested as possible mediators of these disparities. Aims: This study examined whether family conflict, discrimination, and trauma mediate the associations between SGM identity and adverse outcomes, including suicide attempt, major depressive disorder (MDD), nicotine use, and marijuana use. Methods: Participants were children from the Adolescent Brain Cognitive Development (ABCD) study. SGM identity was reported at baseline, while outcomes included past MDD and suicide attempts as well as future nicotine and marijuana use. Structural equation modeling (SEM) was used to test both direct and indirect pathways linking SGM identity to mental health and behavioral outcomes. Results: No significant mediation was found through family conflict, discrimination, or trauma. Instead, effects of SGM identity were primarily direct: SGM youth had higher odds of past suicide attempts and MDD, as well as future marijuana use, but not future nicotine use. Stressor variables, however, were independently associated with outcomes. Discrimination predicted all outcomes; trauma was positively associated with suicide, nicotine, and marijuana use but not MDD; and family conflict predicted all outcomes except MDD. Conclusion: Family conflict, discrimination, and trauma did not mediate SGM disparities in mental health and substance use, but each emerged as an independent predictor of risk. These findings highlight the complexity of mechanisms underlying SGM-related disparities and suggest the need for future research to explore additional pathways and contextual influences.

Background: Emotional problems have been associated with substance use, yet longitudinal research examining this relationship during childhood and adolescence in large, diverse, community-based samples remains limited. Aims: This study investigates the prospective associations between three emotional problems—hopelessness, depression, and suicide attempts—before ages 9–10 and the subsequent initiation of tobacco and marijuana use before ages 14–15, using data from the Adolescent Brain Cognitive Development (ABCD) study. Methods: Data from the ABCD study were analyzed. Baseline emotional problems, including hopelessness, depression, and suicide attempts, were assessed at ages 9–10 through structured parent interviews. Substance use outcomes (tobacco and marijuana initiation) were tracked from baseline to follow-up at ages 14–15 using structured self-report measures. Structural Equation Modeling (SEM) was employed to assess the predictive roles of these early-life emotional problems, controlling for potential confounders such as demographic factors and family and neighborhood socioeconomic status. Results: Baseline hopelessness, depression, and suicide attempts at ages 9–10 were significant predictors of tobacco and marijuana use initiation at ages 14–15. These associations remained robust after adjusting for confounders, indicating the independent effects of early emotional problems on adolescent substance use initiation. Conclusions: Emotional problems in early childhood, including hopelessness, depression, and suicidal behavior, are critical predictors of substance use initiation during adolescence. These findings underscore the importance of early identification and targeted mental health interventions to reduce the risk of substance use among vulnerable youth.