Altered reward-related resting-state network properties in adolescent cannabis use and depression.

Background: Cannabis use among adolescents with depression is prevalent. Dysfunction of the reward system has been implicated in each condition separately, yet rarely examined together. Here, we investigated resting-state properties of reward networks in an adolescent sample with diverse internalizing psychopathology and cannabis use patterns.

Methods: Clinicians interviewed adolescents and assessed depression severity dimensionally. Cannabis use was characterized by self-report and toxicology screens. Neuroimaging scans were acquired and processed using the Human Connectome Project pipelines. Participant-level resting state data were parcellated, and Reward Expectancy and Reward Attainment network masks derived from a reward task were applied. Graph theoretical metrics, including Strength Centrality (CStr), Eigenvector Centrality (CEig), and Local Efficiency (ELoc), were estimated within each network. Group-level clinical correlates of network properties were assessed with non-parametric analyses (10,000 permutations), adjusted for age, sex, and family-wise error (FWE) rates (pFWE < 0.05).

Results: In the full sample (N = 131; 15.3 ± 2.2 years; 65.7% female), depression severity was associated with stronger ELoc of the ventral striatum within the Reward Attainment network. Among those who used cannabis (n = 38), heavier cannabis use was linked to weaker CStr of the anterior cingulate cortex and ELoc of the postcentral somatosensory area within the Reward Expectancy network. Exploratory analyses further suggested cannabis-related dorsolateral prefrontal and cerebellar dysconnectivity across the whole brain, as well as sex- and age-moderated effects.

Conclusion: Our findings provide preliminary evidence for adolescent cannabis use and depression being differentially associated with resting-state reward network properties. Additional research with larger cohort sizes is needed to corroborate findings.