Glutamate Probes in Adolescent Depression

项目概要/摘要 本提案旨在完成K23指导的以患者为导向的研究职业发展奖 培训和研究经验需要准备候选人作为一个成功的职业生涯独立 调查员候选人的长期目标是在学术儿童和青少年精神病学的职业生涯集中 致力于改善抑郁症患者护理的研究。这将通过增加 了解其病理生理学。抑郁症是儿童时期的一种重要而常见的疾病， 这是一个重大的公共卫生问题，也是全世界残疾的主要原因。最近的基础科学和临床 对成年抑郁症患者的研究表明，大脑中主要的兴奋性神经递质谷氨酸盐 在抑郁症的神经化学基础中发挥作用。关于其功能的信息很少。 谷氨酸在青少年抑郁症中的作用质子磁共振波谱（1H-MRS）是一种 一种非侵入性的脑成像技术，可以测量大脑化学物质（如谷氨酸）的浓度。 皮质内易化（ICF）是一种经颅磁刺激（TMS）神经生理学测试， 测量谷氨酸的功能候选人建议在横断面中使用1H-MRS和ICF 青少年抑郁症[三组]受试者谷氨酸浓度和功能的研究 （尚未服用抗抑郁药物的抑郁受试者， 对抗抑郁药有反应，以及健康对照）。【抑郁的受试者会有这两项措施 用氟西汀标准临床治疗8周后重复。这将检验假设， 皮质谷氨酸浓度降低，而谷氨酸功能在青少年中增加， 抑郁症和氟西汀的成功治疗使这些差异正常化。这一创新 这种方法将促进对青少年抑郁症中谷氨酸神经传递的理解， 开发新的生物标志物，并协助确定治疗靶点。这个项目是量身定制的 为随后的联邦R 01拨款申请的抑郁青少年纵向研究提供信息。的 候选人之前有ICF测量经验，但将受益于1H-MRS的额外培训 方法学和TMS神经生理学范例。候选人和指导团队提出职业生涯 开发计划侧重于1H-MRS神经成像、TMS神经生理学研究、临床和转化 研究方法，[神经发育，]和疾病研究的神经生物学。这个严格的计划 包括密集的指导，通过马约诊所研究生院的课程，和国际研讨会。 关于出版物和赠款提交的明确界定的基准将确保大量的生产力 在获奖期间，并成功地过渡到一个独立的学术研究人员在儿童和 青少年精神病学

PROJECT SUMMARY / ABSTRACT This proposal is for a K23 Mentored Patient-Oriented Research Career Development Award to complete training and research experience needed to prepare the candidate for a successful career as an independent investigator. The candidate's long-term goal is a career in academic child and adolescent psychiatry focused on research that improves the care of patients with depression. This will be accomplished through increased understanding of its pathophysiology. Depression is a significant and common illness during childhood, a major public health problem, and a leading causes of disability worldwide. Recent basic science and clinical research in adults with depression suggests that glutamate, the brain's primary excitatory neurotransmitter plays a role in the neurochemical basis of depression. There is little information about the functioning of glutamate in adolescents with depression. Proton magnetic resonance spectroscopy (1H-MRS) is a noninvasive brain imaging technique that measures the concentrations of brain chemicals such as glutamate. Intracortical facilitation (ICF) is a transcranial magnetic stimulation (TMS) neurophysiological test which measures the functioning of glutamate. The candidate proposes to use 1H-MRS and ICF in a cross-sectional study of glutamate concentrations and functioning in adolescent depression [with three groups] of subjects (depressed subjects who have not yet taken an antidepressant medication, subjects who had depression that responded to an antidepressant, and healthy controls). [Depressed subjects will have these two measures repeated after eight weeks of standard clinical treatment with fluoxetine. This will test the hypotheses that cortical glutamate concentrations are decreased while glutamate functioning is increased in adolescents with depression and that successful treatment with fluoxetine normalizes these differences.] This innovative approach will advance understanding of glutamate neurotransmission in adolescent depression, inform the development of new biomarkers, and assist with the identification of treatment targets. This project is tailored to inform subsequent longitudinal studies of depressed adolescents for federal R01 grant applications. The candidate has prior experience with ICF measures but would benefit from additional training in 1H-MRS methodology and TMS neurophysiology paradigms. The candidate and mentoring team propose a career development plan focused on 1H-MRS neuroimaging, TMS neurophysiology studies, clinical and translational research methodologies, [neurodevelopment,] and the neurobiology of disease research. This rigorous plan includes intensive mentoring, courses through the Mayo Clinic Graduate School, and international seminars. Well defined benchmarks regarding publications and grant submissions will ensure substantial productivity during the award period and a successful transition to an independent academic researcher in child and adolescent psychiatry.