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 这份以病人为导向的职业发展奖（K23）的申请将允许候选人 获得新领域的专业培训和研究专长，使她能够成为一个独立的 医学科学家Fischer博士详细介绍了一项旨在描述大麻影响的五年研究计划 暴露对过渡年龄青年（TAY）神经生物学功能和抑郁症状演变的影响。 具体目的是前瞻性地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指导模型 奖励受损和抑郁症状的研究。40名常规大麻使用者和30名非大麻使用者- 将招募使用对照的受试者并前瞻性随访12个月。参与者将完成临床和 物质使用评估，利用功能性神经成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，以量化总的δ-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， 大麻暴露在TAY。该应用程序建立在候选人先前的研究经验，在表征 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， 抑郁症的恢复力和治疗反应。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）多层面 奖励处理和损伤的表征;（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的大麻和抑郁症研究。一个跨学科的导师团队，他们是 与药物滥用有关的奖励功能和损害的表征（Knutson博士），植物/内分泌- 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），以及用于分析的统计方法 纵向数据（乔博士）将帮助候选人满足她的培训和研究目标。该方案 研究和培训直接与NIDA和NIMH战略计划和优先事项保持一致， 描述在未充分研究期间大麻暴露的神经生物学和精神病学影响 使用定量、多变量和纵向评估来研究大脑发育。费舍尔博士的研究 培训将在斯坦福大学进行。这个K23职业发展奖将提供一个基本的 为候选人实现其表征大麻纵向效应的职业目标奠定了基础 暴露于与临床症状相关的神经生物学功能，从而告知公共政策， 协助开发针对大麻使用和抑郁症的神经生物学指导干预措施， 紊乱