Studies of Amino Acid Neurotransmitter Contributions to Depression

描述（由申请人提供）：此KO 2申请寻求支持，这是至关重要的博士Sanacora的继续职业发展作为一个新的独立的临床研究人员。由NIMH K 08指导职业奖（K 08-MH-01715）资助，Sanacora博士在过去5年中在使用磁共振波谱作为研究氨基酸神经递质系统在病理生理学和情绪障碍治疗中的作用的工具方面获得了相当多的专业知识。由于Sanacora博士获得的指导以及通过磁共振中心和耶鲁大学精神病学系为他提供的良好环境，他在这段时间内表现出相当大的研究生产力，这一点可以从他的同行评审出版物和最近获得的RO 1（MH 071676 -01，G. Sanacora，P.I.）。然而，该K 08于2004年6月31日到期。这个KO 2奖对于维持Sanacora博士目前的全职研究重点和确保他成功进入完全独立的研究人员至关重要。该奖项的理由是提供了一个全面的5年职业发展计划，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和用于调查这一领域的MRS方法的专业知识基础上。具体来说，他的目标是获得几个额外领域的专业技能，使他能够将这项工作扩展到更直接的科学和临床意义的领域：1）测量合成和循环速率的13 C-葡萄糖MRS方法，2）探测神经胶质细胞参与情绪障碍病理的13 C-乙酸盐研究，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有用性，以及4）与氨基酸神经传递相关的基础分子神经生物学，使他能够继续进行心境障碍的相关转化研究。强化培训是由校内课程，校外教学法，个性化的preceptorships，互动研讨会和研究相关的组织会议的综合课程。包括三个代表性的研究，以说明如何发展这些技能将被用来推进线的研究，这是在他以前的K 08奖开始进入病理生理学和临床实践的领域。因此，获得这个奖项将使他有机会提高氨基酸神经递质系统和神经胶质细胞病理学如何有助于情绪障碍的神经生物学的基本理解。这项工作具有直接的临床意义，因为它很可能导致这些疾病的新的诊断方法和治疗方式的发展。

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.