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

产前大麻暴露在青少年奖励相关神经回路和精神病样经历中的作用

• 批准号: 10752372
• 负责人: Carolyn Amir
• 金额: $ 4.26万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10752372
• 关键词: Adolescence; Adolescent; Adverse effects; Affect; Age; Age of Onset; Animals; Behavioral; Biological Factors; Biological Markers; Brain; Brain region; California; Cannabis; Child; Child Development; Childhood; Clinical; Collaborations; Corpus striatum structure; Data; Development; Dose; Early Intervention; Environment; Environmental Risk Factor; Exposure to; Foundations; Functional Magnetic Resonance Imaging; Future; Impairment; Individual; Knowledge; Link; Literature; Longevity; Los Angeles; Machine Learning; Mental Health; Modeling; Neurobiology; Neurocognitive Deficit; Neurosciences; Outcome; Parents; Participant; Pathway interactions; Patients; Pattern; Plants; Policy Maker; Pregnancy; Pregnant Women; Psychopathology; Psychoses; Psychotic Disorders; Public Health; Recording of previous events; Recreation; Reporting; Research; Rewards; Risk; Risk Factors; Role; Sampling; Severities; Shapes; Site; Statutes and Laws; Substance Use Disorder; Symptoms; Techniques; Tetrahydrocannabinol; Time; Training; United States; Universities; Work; Youth; cognitive development; cohort; design; fetal marijuana exposure; financial incentive; follow-up; functional disability; high risk; improved; indexing; insight; longitudinal, prospective study; machine learning classifier; marijuana use; marijuana use disorder; marijuana use in pregnancy; neural; neural circuit; neuroimaging; offspring; permissiveness; preadolescence; predictive modeling; prenatal; prepuberty; programs; psychosis risk; psychosocial; psychotic; psychotic symptoms; psychotic-like experiences; reward anticipation; reward circuitry; reward processing; substance use

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.

项目总结