The Role of Prenatal Cannabis Exposure in Reward-related Neural Circuitry and Psychotic-like Experiences in Youth

PROJECT SUMMARY
Cannabis use is becoming increasingly common in the US, and past-month use among pregnant women
increased by almost 60% from 2003 to 2019. Despite increasingly permissive legislation, our knowledge of the
behavioral and neurobiological consequences of prenatal exposure to cannabis and delta-9-
tetrahydrocannabinol (THC) lags behind. Hazardous cannabis use has been linked to psychosis onset and
psychotic-like experiences throughout the lifespan, and both cannabis use and psychosis have overlapping
neural foundations in reward circuitry. However, the effects of prenatal cannabis exposure on youth
psychopathology are not yet known. Reward pathways implicated in cannabis use disorder and psychosis offer
key insights into how prenatal cannabis exposure may shape psychosis outcomes; functional brain alterations
during reward anticipation may represent a biomarker of disrupted reward processing. To enable the
development of early interventions and the discovery of robust biomarkers of psychosis risk, it is imperative to
determine relationships between neural and behavioral indices associated with hazardous cannabis use and
psychosis across development and inform predictive models. A unique opportunity to advance this work is
provided by the Adolescent Brain Cognitive Development (ABCD) Study, a 10-year national collaboration of 21
research sites designed to study the effects of substance use across development. The cohort includes 655
youth ages 9-13 who were exposed to cannabis prenatally and 10,834 who were not. Specially, the project aims
are to: 1) characterize longitudinal associations between prenatal cannabis exposure and psychotic-like
experiences (PLEs) across two years of follow-up; and 2a) Predict PLEs via machine learning classifiers built on
baseline psychosocial and environmental psychosis risk factors, including prenatal cannabis exposure, and 2b)
Predict PLEs via machine learning classifiers built on multivariate pattern analysis of neural activity in reward-
related brain regions during reward anticipation in a monetary incentive delay fMRI task. The results of the study
will have immediate public health and clinical implications providing clinicians, patients, and policymakers with
critical data on the impacts of prenatal cannabis exposure on youth mental health outcomes. Additionally, results
will aid in development of models for predicting psychosis risk during child development and inform future studies
on effects of in utero cannabis exposure. Completion of the training plan proposed here will provide essential
training in longitudinal modeling, neuroimaging approaches including task-based functional MRI (fMRI) and
machine learning techniques crucial to completing these aims. The Bearden and Cooper Labs and the
Neuroscience Interdepartmental Program at the University of California, Los Angeles will provide the ideal
training environments for the successful completion of this proposal.

Grant Number: 5F31DA060068-03
NIH Institute/Center: NIH
Principal Investigator: Carolyn Amir