Cannabis, Depression and Neurobiological Function in Transition-Age Youth

过渡时期青年的大麻、抑郁症和神经生物学功能

• 批准号: 10370928
• 负责人: Adina Sheri Fischer
• 金额: $ 19.33万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-15 至 2029-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10370928
• 关键词: Acute; Address; Adolescent; Adolescent and Young Adult; Adrenal Glands; Adult; Age; Anhedonia; Animals; Area; Attention; Biological Assay; Biological Markers; Brain; Cannabinoids; Cannabis; Chronic; Clinical; Data; Depressive disorder; Development; Dimensions; Disease; Education; Endocannabinoids; Evolution; Exposure to; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Generations; Goals; Hair; Harm Reduction; Hydrocortisone; Hypothalamic structure; Impairment; Individual; Intervention; Investigation; K-Series Research Career Programs; Knowledge; Learning; Legal; Link; Major Depressive Disorder; Mass Spectrum Analysis; Measures; Medial; Mediating; Mediation; Mental Depression; Mentors; Methods; Modeling; Modernization; National Institute of Drug Abuse; National Institute of Mental Health; Neurobiology; Nucleus Accumbens; Outcome; Participant; Patients; Persons; Pharmacology; Phenotype; Physicians; Physiology; Pituitary Gland; Prefrontal Cortex; Psychotic Disorders; Public Health; Public Policy; Recording of previous events; Research; Research Training; Rewards; Risk; Risk Factors; Rodent; Sampling; Scientist; Serum; Signal Transduction; Statistical Methods; Strategic Planning; Stress; Stress Tests; Substance abuse problem; Suicide; Symptoms; System; THC exposure; Tetrahydrocannabinol; Training; United States; Universities; Work; Youth; acute stress; addiction; age group; base; biological adaptation to stress; career; career development; child depression; depressive symptoms; design; disability; endocannabinoid signaling; endogenous cannabinoid system; experience; financial incentive; follow-up; longitudinal analysis; marijuana use; marijuana user; neuroimaging; patient oriented; programs; prospective; psychiatric symptom; recruit; resilience; response; reward anticipation; reward circuitry; reward processing; sex; substance use; task analysis; treatment response; virtual

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.

项目摘要 该申请申请受到指导的以患者为导向的职业发展奖（K23）将使候选人能够 在新领域获得专业培训和研究专业知识，使她成为独立 医师科学家。 Fischer博士详细介绍了一个五年的研究计划，旨在表征大麻的影响 过渡年龄青年（TAY）中神经生物学功能的暴露和抑郁症状的演变。 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，并开发大麻暴露作用的初步综合生物标志物引导模型 关于奖励障碍和抑郁症的症状。四十种常规大麻用户和30个非大麻 使用控制措施将被招募并前瞻性持续12个月。参与者将完成临床和 使用功能神经成像和皮质醇的药物使用评估，进行奖励和压力测试 生物测定，并提供头发样品来量化骨料的骨料Delta-9-四氢大麻酚（THC）暴露。 这项工作的发现将提高我们对神经生物学和精神病的理解 大麻暴露于泰。该申请基于候选人的先前研究经验 大麻在双疾病患者中的急性影响并检查具有风险的功能连通性生物标志物， 抑郁症的弹性和治疗反应。在K23的整个过程中，Fischer博士将深入了解 在她的职业发展至关重要的新领域的指导培训：（1）多维 奖励处理和损害的表征； （2）Phyto/内托 - 大麻素的神经生物学和 下丘脑 - 垂体 - 肾上腺（HPA）应力轴； （3）纵向研究和分析 TAY中的转化大麻和抑郁研究。一个跨学科的导师团队，他们是专家 与药物滥用有关的奖励功能和损害的表征（Knutson博士），Phyto/endo- 大麻素药理学和生理学（Piomelli博士），HPA胁迫轴生理学和病理生理学 抑郁症（Schatzberg博士），青少年大麻研究（Tapert博士）和分析统计方法 纵向数据（JO博士）将帮助候选人达到她的培训和研究目标。这个程序的 研究和培训直接与NIDA和NIMH的战略计划和优先级保持一致 表征大麻暴露在知识期间的神经生物学和精神病的影响 使用定量，多元和纵向评估的大脑发育。 Fischer博士的研究和 培训将在斯坦福大学举行。这个K23职业发展奖将提供基本 候选人实现她的职业目标的基础，以表征大麻的纵向影响 与临床症状有关的神经生物学功能接触 协助开发用于大麻使用和抑郁的神经生物学指导的干预措施 疾病。