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.

项目概要 大麻的使用在美国变得越来越普遍，过去一个月孕妇的大麻使用情况 从 2003 年到 2019 年，增加了近 60%。尽管立法越来越宽松，但我们对 产前接触大麻和 delta-9- 的行为和神经生物学后果 四氢大麻酚（THC）落后。危险的大麻使用与精神病的发作有关 整个生命周期都有类似精神病的经历，并且吸食大麻和精神病有重叠 奖励电路的神经基础。然而，产前接触大麻对青少年的影响 精神病理学尚不清楚。与大麻使用障碍和精神病相关的奖励途径 关于产前大麻暴露如何影响精神病结果的关键见解；大脑功能改变 在奖励预期期间可能代表奖励处理中断的生物标志。要启用 发展早期干预措施并发现精神病风险的强大生物标志物，势在必行 确定与危险大麻使用相关的神经和行为指数之间的关系 整个发展过程中的精神病并为预测模型提供信息。推进这项工作的一个独特的机会是 由青少年大脑认知发展 (ABCD) 研究提供，这是一项为期 10 年的全国性合作，由 21 旨在研究物质使用对发展的影响的研究网站。该队列包括 655 9 至 13 岁的青少年在产前接触过大麻，另有 10,834 名青少年未接触过大麻。特别地，该项目的目标是 目的是：1）描述产前大麻暴露与精神病样症状之间的纵向关联 两年随访期间的经验（PLE）； 2a) 通过基于机器学习的分类器预测 PLE 基线社会心理和环境精神病风险因素，包括产前大麻暴露，以及 2b) 通过基于奖励神经活动的多元模式分析的机器学习分类器来预测 PLE 在金钱激励延迟功能磁共振成像任务中奖励预期期间的相关大脑区域。研究结果 将产生直接的公共卫生和临床影响，为临床医生、患者和政策制定者提供 关于产前接触大麻对青少年心理健康结果影响的关键数据。另外，结果 将有助于开发预测儿童发育期间精神病风险的模型，并为未来的研究提供信息 关于子宫内大麻暴露的影响。完成此处提出的培训计划将提供必要的 纵向建模、神经影像方法（包括基于任务的功能磁共振成像 (fMRI) 和 机器学习技术对于实现这些目标至关重要。比尔登和库珀实验室以及 加州大学洛杉矶分校的神经科学跨系项目将提供理想的 成功完成本提案的培训环境。