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

Prenatal cannabis exposure is linked to psychotic-like experiences in youth, and this relationship may involve disrupted reward-related brain function. In a large longitudinal study of children aged 9–10 at baseline, those with prenatal cannabis exposure (652 children) showed blunted neural response to reward anticipation, which was associated with psychotic-like experiences and predicted psychosis symptoms in middle adolescence. Dampened behavioral reward sensitivity was also associated with psychotic-like experiences across follow-ups. Trait-level measures of reward motivation and impulsivity were more strongly linked to psychotic-like experiences in children with prenatal cannabis exposure. Blunted activation in reward-related brain regions may be a biomarker for increased psychosis risk.

Study at a glance

Abstract

Abstract Importance Rates of prenatal cannabis exposure (PCE) are rising with increasingly permissive legislation regarding cannabis use, which may be a risk factor for psychosis. Disrupted reward-related neural circuitry may underlie this relationship. Objective To elucidate neural mechanisms involved in the association between PCE and youth-onset psychotic-like experiences by probing correlates of reward anticipation, a neurobehavioral marker of endocannabinoid-mediated dopaminergic function. Design, setting, and participants 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 psychotic-like experiences. Blunted neural response to reward anticipation is associated with psychotic-like experiences, with stronger effects observed in PCE youth (all |β| > 0.5; false discovery rate [FDR]–corrected P < .05). This hypoactivation at baseline predicts psychosis symptomatology in middle adolescence (4-year follow-up visit; β=-.004; FDR-corrected P < .05). Dampened behavioral reward sensitivity is associated with psychotic-like experiences across baseline, 2-year follow-up visit, and 4-year follow-up visit (|β| = .21; FDR-corrected P < .001). Psychotic-like experiences 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 and Relevance Blunted activation in reward-related brain regions 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.