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

Carolyn M. Amir, Dara G. Ghahremani, Sarah E. Chang, Ziva D. Cooper, Carrie E. Bearden

preprint DOI: 10.1101/2024.08.23.24312453 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Longitudinal prospective study
Sample size 11,368
Population Children aged 9 to 10 years old at baseline from 22 sites across the United States
Duration 4-year follow-up
Topics Cannabis
Key findings Prenatal cannabis exposure is longitudinally associated with psychotic-like experiences, and blunted neural response to reward anticipation predicts psychosis symptomatology in middle adolescence.

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.