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.

项目概要 申请以患者为导向的职业发展奖（K23）将使候选人能够 获得新领域的专门培训和研究专业知识，使她能够成为独立的 医生科学家费舍尔博士详细介绍了旨在表征大麻影响的五年研究计划。 暴露于过渡年龄青年（TAY）的神经生物学功能和抑郁症状的演变。 具体目标是前瞻性研究大麻暴露对奖励和压力系统的影响 功能，并开发大麻暴露影响的初步综合生物标志物引导模型 TAY 中 40 名经常吸食大麻的人和 30 名不吸食大麻的人的奖赏受损和抑郁症状。 将招募使用对照的参与者并进行为期 12 个月的前瞻性随访。 物质使用评估，利用功能性神经影像和皮质醇进行奖励和压力测试 生物测定，并提供头发样本来量化 delta-9-四氢大麻酚 (THC) 的总暴露量。 这项工作的发现将增进我们对神经生物学和精神病学后果的理解 TAY 中的大麻暴露该申请建立在候选人之前的表征研究经验的基础上。 大麻对双重疾病患者的急性影响并检查风险的功能连接生物标志物， 在 K23 课程中，Fischer 博士将深入了解抑郁症的恢复力和治疗反应。 对她的职业发展至关重要的新领域的指导培训：(1) 多维 奖励处理和损伤的特征；（2）植物/内源性大麻素的神经生物学和 下丘脑-垂体-肾上腺（HPA）应力轴；（3）纵向调查和分析 TAY 的转化大麻和抑郁症研究由专家组成的跨学科导师团队。 奖赏功能的特征和与药物滥用相关的损害（Knutson 博士），phyto/endo- 大麻素药理学和生理学（Piomelli 博士）、HPA 应激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）以及统计分析方法 纵向数据（Jo 博士）将帮助候选人实现她的培训和研究目标。 研究和培训与 NIDA 和 NIMH 战略计划和优先事项直接保持一致 描述在研究期间接触大麻对神经生物学和精神影响的特征 使用定量、多变量和纵向的大脑发育评估。 培训将在斯坦福大学进行，K23 职业发展奖将提供基础知识。 为候选人实现描述大麻纵向影响的职业目标奠定基础 暴露与临床症状相关的神经生物学功能，从而为公共政策和 协助制定针对大麻使用和抑郁症的神经生物学指导干预措施 失调。