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

项目摘要 大麻的使用在美国变得越来越普遍，孕妇的上个月使用 从2003年到2019年增长了近60%。尽管立法越来越宽松，但我们对 产前暴露于大麻和δ-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发作有关， 在整个生命周期中，大麻使用和精神病都有重叠 奖赏回路的神经基础然而，产前接触大麻对青年的影响 精神病理学尚不清楚。涉及大麻使用障碍和精神病的奖励途径提供 产前大麻暴露如何影响精神病结果的关键见解;功能性大脑改变 在奖励预期期间可以表示中断的奖励处理的生物标记。使 发展早期干预措施和发现精神病风险的强大生物标志物， 确定与危险大麻使用相关的神经和行为指数之间的关系， 精神病跨越发展，并为预测模型提供信息。推进这项工作的一个独特机会是 由青少年大脑认知发展（ABCD）研究提供，该研究是一项为期10年的全国性合作， 旨在研究物质使用对整个发展的影响的研究网站。该队列包括655名 9-13岁的青少年在产前接触大麻，10，834人没有。特别是，该项目旨在 （1）描述产前大麻暴露与精神病样 2a）通过基于以下内容构建的机器学习分类器预测PLEs： 基线心理社会和环境精神病风险因素，包括产前大麻暴露，以及2b） 通过基于奖励中神经活动的多变量模式分析的机器学习分类器预测PLEs- 在金钱激励延迟fMRI任务中，相关脑区在奖励预期中的作用。研究结果 将对公共卫生和临床产生直接影响，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年心理健康结果影响的关键数据。此外，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。 子宫内接触大麻的影响完成这里提出的培训计划将提供必要的 纵向建模培训，神经成像方法，包括基于任务的功能性MRI（fMRI）， 机器学习技术对实现这些目标至关重要。比尔登和库珀实验室 加州大学洛杉矶分校的神经科学跨部门项目将提供理想的 培训环境，以顺利完成本提案。

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.