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

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 = 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.

Results: 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).

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.