Altered Neurobehavioral Reward Response Predicts Psychotic-Like Experiences in Youth Exposed to Cannabis Prenatally

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.

This longitudinal, prospective study analyzed task-related functional neuroimaging data from baseline (N = 11,368), 2-year follow-up (n = 7928), and 4-year follow-up (n = 2982) of the ongoing ABCD (Adolescent Brain Cognitive Development) Study, which recruited children ages 9 to 10 years at baseline from 22 sites across the United States.

PCE (652 exposed youths) was longitudinally associated with PLEs. Blunted neural response to reward anticipation was associated with PLEs, with stronger effects observed in PCE youths (all |βs| > 0.5; false discovery rate [FDR]-corrected p < .05). This baseline hypoactivation predicted PLEs in middle adolescence (β = -0.004; p_FDR < .05) and mediated the relationship between PCE and PLEs. Dampened behavioral reward sensitivity was associated with PLEs across visits (|β| = 0.21; p_FDR < .001). PLEs were positively associated with trait-level measures of reward motivation and impulsivity, with stronger effects for PCE youths (all |βs| > 0.1; all p_FDR < .05).

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.