Studies of Amino Acid Neurotransmitter Contributions to Depression

描述(由申请人提供)：这份KO2申请寻求对Sanacora博士作为一名新独立的临床研究人员的持续职业发展至关重要的支持。在NIMH K08指导职业奖(K08-MH-01715)的资助下，Sanacora博士在过去5年中利用磁共振波谱作为工具来研究氨基酸神经递质系统在情绪障碍的病理生理学和治疗中的作用方面获得了相当多的专业知识。多亏了萨纳科拉博士得到的指导，以及通过磁共振中心和耶鲁精神病学系为他提供的良好环境，他在这段时间内表现出了相当大的研究效率，他的同行评议出版物和最近授予的RO1(MH071676-01，G.Sanacora，P.I.)证明了这一点。然而，此K08在04年6月31日到期。这一KO2奖项对于维持Sanacora博士目前的全职研究重点以及确保他成功进入完全独立的研究人员至关重要。该奖项由一份全面的5年职业发展计划提供，该计划建立在他目前在研究氨基酸神经递质对情绪障碍的贡献方面的专业知识，以及用于研究这一领域的MRS方法。具体地说，他的目标是在其他几个领域获得专门技能，使他有可能将这项工作扩展到更直接的科学和临床意义领域：1)13C-葡萄糖MRS方法测量合成和循环速率，2)13C-乙酸酯研究，以探索神经胶质细胞在情绪障碍病理中的参与，3)临床试验经验，使他能够解决针对氨基酸神经递质系统的药物的潜在临床实用性，以及4)与氨基酸神经传递相关的基础分子神经生物学，这将使他能够继续在情绪障碍中进行相关的翻译研究。强化培训由综合课程提供，包括校内课程、校外教学、个人化授课、互动研讨会和与研究有关的组织会议。其中包括三项具有代表性的研究，以说明如何利用这些技能的发展来推进他在上一次K08奖中发起的研究路线，进入病理生理学和临床实践领域。因此，获得这一奖项将使他有机会提高对氨基酸神经递质系统和神经胶质细胞病理学如何对情绪障碍的神经生物学做出贡献的基本理解。这项工作具有直接的临床意义，因为它可能导致这些疾病的新诊断方法和治疗模式的发展。

DESCRIPTION (provided by applicant): This KO2 application seeks support that is essential for Dr. Sanacora's continued career development as a newly-independent clinical researcher. Funded by a NIMH K08 mentored career award (K08-MH-01715) Dr. Sanacora has attained considerable expertise in the use of magnetic resonance spectroscopy as a tool to investigate the role of amino acid neurotransmitter systems in the pathophysiology and treatment of mood disorders over the past 5 years. Thanks to the mentorship Dr. Sanacora received and the excellent environment provided to him through the Magnetic Resonance Center and the Department of Psychiatry at Yale he demonstrated considerable research productivity during this time as evidenced by his peer-reviewed publications and a recently-awarded RO1 (MH071676-01, G. Sanacora, P.I.). However, this K08 expired 6/31/04. This KO2 award is vital for sustaining Dr. Sanacora's current full-time research focus and for assuring his successful matriculation into a fully independent investigator. Justification for the award is provided by a comprehensive 5-year Career Development Plan that builds on his current expertise in the study of amino acid neurotransmitter contributions to mood disorders and the MRS methodologies used to investigate this area. Specifically, his goals are to acquire specialized skills in several additional areas that will make it possible for him to extend this work into areas of more direct scientific and clinical significance: 1) 13C-glucose MRS methods to measure rates of synthesis and cycling, 2) 13C-acetate studies to probe glial cell involvement in mood disorder pathology, 3) clinical trial experience to allow him to address the potential clinical usefulness of drugs targeting the amino acid neurotransmitter systems, and 4) basic molecular neurobiology related to amino acid neurotransmission that will enable him to continue to conduct relevant translational research in mood disorders. Intensive training is provided by an integrated curriculum of intramural coursework, extramural didactics, individualized preceptorships, interactive symposia, and research-related organizational meetings. Three representative studies are included to illustrate how the development of these skills will be used to advance the line of research that was initiated in his previous K08 award into the realms of pathophysiology and clinical practice. Thus, receiving this award would allow him the opportunity to improve the basic understanding of how the amino acid neurotransmitter systems and glial cell pathology contribute to the neurobiology of mood disorders. This work has direct clinical relevance since it is likely to lead to the development of novel diagnostic methods and treatment modalities for these disorders.