Neural Correlates of Reward Dysfunction in Adolescent Cannabis Use and Depression

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Abstract Objective Cannabis use is prevalent among youth with depression and may alter the reward neurocircuitry, which also plays a role in depression. Yet, reward function in co-occurring cannabis use and depression remains poorly understood. Here, we sought to examine neural reward processing in an adolescent sample with varying cannabis use and depression severity. Methods Participants completed diagnostic interviews and self-reported depression symptoms dimensionally. Cannabis use patterns were determined from clinician interviews, self-reports, and urine toxicology screens. Structural and Reward Flanker Task functional MRI data were collected and preprocessed using Human Connectome Project-style pipelines. Using a parcellated, network-based approach, we examined neural responses during reward expectancy (reward vs. non-reward cues) and attainment (reward vs. non-reward feedback) in relation to cannabis use and depression severity, controlling for age, sex, and multiple comparisons. Results In the full sample of 117 adolescents (age: 15.5 ± 2.3 years, 63.3% female), greater depression severity was linked to blunted caudate activity during reward expectancy and heightened activation of posterior cingulate and entorhinal cortices during reward attainment. Among 34 adolescents who used cannabis, heavier use was associated with greater activation in the left mediodorsal posterior thalamus and habenula during reward expectancy, while depression severity positively correlated with activation across cortico-striatal, default, memory, and visual networks during reward attainment. Cannabis use × depression interaction effects were detected in frontal and entorhinal cortices during reward attainment. Exploratory analyses showed sex differences. Conclusions Our results reveal divergent neural profiles of cannabis use and depression, as well as their additive associations with altered reward processing in adolescents.

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