Altered neurobehavioral reward response predicts psychotic-like experiences in youth exposed to cannabis prenatally.

Abstract

Background: Rates of prenatal cannabis exposure (PCE) are rising with increasingly permissive legislation, which may be a risk factor for psychosis. Disrupted reward-related neural circuitry may underlie this relationship. We aim to elucidate neural mechanisms involved in the association between PCE and youth-onset psychotic-like experiences (PLEs) by probing correlates of reward anticipation, a neurobehavioral marker of endocannabinoid-mediated dopaminergic function.

Methods: This longitudinal, prospective study analyzed task-related functional neuroimaging data from baseline (n=11,368), 2-year follow-up (n=7,928), and 4-year follow-up (n=2,982) of the ongoing Adolescent Brain and Cognitive Development (ABCD) Study, which recruited children aged 9 to 10 years old at baseline from 22 sites across the United States.

Results: PCE (n=652 exposed youth) is longitudinally associated with PLEs. Blunted neural response to reward anticipation is associated with PLEs, with stronger effects observed in PCE youth (all |β|> 0.5; false discovery rate [FDR]-corrected P < .05). This baseline hypoactivation predicts PLEs in middle adolescence (β=-.004; FDR-corrected P < .05) and mediates the relationship between PCE and PLEs. Dampened behavioral reward sensitivity is associated with PLEs across visits (|β| = .21; FDR-corrected P < .001). PLEs are positively associated with trait-level measures of reward motivation and impulsivity, with stronger effects for PCE youth (all |β| > 0.1; all FDR-corrected P < .05).

Conclusions: Blunted striatal activation may serve as a biomarker for disrupted reward processing and increased psychosis risk during development. PCE may affect childhood behaviors and traits related to altered reward sensitivity.