Cannabis, Depression and Neurobiological Function in Transition-Age Youth

项目摘要 这份以患者为导向的职业发展指导奖(K23)的申请书将允许候选人 获得新领域的专门培训和研究专业知识，使她能够成为一名独立的 内科科学家。费舍尔博士详细介绍了一项旨在描述大麻影响的五年研究计划 过渡期青年(Tay)神经生物学功能和抑郁症状演变的暴露。 具体目的是前瞻性地检查大麻暴露对奖励和压力系统的影响。 功能，并开发一个初步的综合生物标记物引导的大麻暴露影响的模型 泰的奖赏障碍和抑郁症状的研究。40个经常吸食大麻的人和30个不吸大麻的人- 将招募使用对照的人，并前瞻性地跟踪观察12个月。参与者将完成临床和 物质使用评估，利用功能神经成像和皮质醇执行奖励和压力测试 生物测试，并提供头发样本，以量化总的三角洲-9-四氢大麻酚(THC)暴露。 这项工作的发现将促进我们对神经生物学和精神病学后果的理解 在泰州暴露于大麻。该应用程序建立在候选人以前的研究经验的基础上 大麻对双重障碍患者的急性影响和检测风险的功能连接生物标记物， 抑郁症的复原力和治疗反应。在K23的过程中，费舍尔博士将接受深入的 在对她的职业发展至关重要的新领域进行指导-培训：(1)多维 奖赏加工和损害的特征；(2)植物/内源性大麻的神经生物学和 下丘脑-垂体-肾上腺(HPA)应力轴；(3)纵向调查分析。 泰的翻译大麻与抑郁症研究。一个跨学科的导师团队，他们是 与药物滥用有关的奖赏功能和损害的特征(Knutson博士)，植物/内源- 大麻素药理学和生理学(Piomelli博士)，HPA应力轴生理学和病理生理学 抑郁症(沙茨伯格博士)、青少年大麻研究(塔普特博士)和统计分析方法 纵向数据(Jo博士)将帮助应聘者达到她的培训和研究目标。这是一项 研究和培训直接与NIDA和NIMH战略计划和优先事项保持一致 未充分研究期间大麻暴露的神经生物学和精神影响的特征 使用定量、多变量和纵向评估对大脑发育进行评估。费舍尔博士的研究和 培训将在斯坦福大学进行。这项K23职业发展奖将提供一个基本的 为候选人实现描述大麻纵向影响的职业目标奠定基础 接触与临床症状有关的神经生物学功能，从而向公众提供政策和信息 协助制定神经生物学指导的大麻使用和抑郁干预措施 精神错乱。

Project Summary This application for a Mentored Patient-Oriented Career Development Award (K23) will allow the candidate to obtain specialized training and research expertise in new areas that will enable her to become an independent physician scientist. Dr. Fischer details a five year research plan aimed at characterizing the effects of cannabis exposure on neurobiological functioning and the evolution of depressive symptoms in transition age youth (TAY). The specific aims are to prospectively examine the impact of cannabis exposure on reward and stress system functioning, and to develop a preliminary integrative biomarker-guided model of the effects of cannabis exposure on symptoms of reward impairment and depression in TAY. Forty regular cannabis-users and 30 non-cannabis- using controls will be recruited and prospectively followed for 12 months. Participants will complete clinical and substance use assessments, perform reward and stress tests utilizing functional neuroimaging and cortisol bioassays, and provide hair samples to quantify aggregate delta-9-tetrahydrocannabinol (THC) exposure. Findings from this work will advance our understanding of the neurobiological and psychiatric consequences of cannabis exposure in TAY. The application builds on the candidate’s prior research experience in characterizing the acute effects of cannabis in dual-disorder patients and examining functional connectivity biomarkers of risk, resilience and treatment response in depression. Over the course of the K23, Dr. Fischer will receive in-depth mentored-training in new areas that are essential to her career development: (1) the multidimensional characterization of reward processing and impairment; (2) the neurobiology of phyto/endo-cannabinoids and the hypothalamic-pituitary-adrenal (HPA) stress axis; and (3) the longitudinal investigation and analysis of translational cannabis and depression research in TAY. An interdisciplinary team of mentors who are experts in the characterization of reward function and impairment in relation to substance abuse (Dr. Knutson), phyto/endo- cannabinoid pharmacology and physiology (Dr. Piomelli), HPA stress-axis physiology and pathophysiology in depression (Dr. Schatzberg), adolescent cannabis research (Dr. Tapert), and statistical methods for analyzing longitudinal data (Dr. Jo) will help the candidate meet her training and research objectives. This program of research and training directly aligns with NIDA and NIMH Strategic Plans and Priorities by rigorously characterizing the neurobiological and psychiatric impact of cannabis exposure during an understudied period of brain development using quantitative, multivariate, and longitudinal assessments. Dr. Fischer’s research and training will take place at Stanford University. This K23 Career Development Award will provide a fundamental foundation for the candidate to achieve her career goals of characterizing the longitudinal effects of cannabis exposure on neurobiological function in relation to clinical symptoms, thereby informing public poloicy and assisting in the development of neurobiologically-guided interventions for cannabis use and depressive disorders.