Cannabis and depression show distinct reward-network changes

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. 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&#xa0;<&#xa0;0.05). In the full sample (N&#xa0;=&#xa0;131; 15.3&#xa0;&#xb1;&#xa0;2.2&#xa0;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&#xa0;=&#xa0;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. 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.