Cerebral Energy Metabolism in Geriatric Bipolar Depression

描述（由申请人提供）：Forester博士的目标是成为老年双相情感障碍领域的独立研究者，使用磁共振波谱（MRS）研究治疗反应的生化标志物。长期职业目标包括与其他使用磁共振成像（MRI）技术的中心合作，研究老年双相情感障碍，重点是开发安全有效的治疗干预措施。Forester博士将在McLean医院接受Bruce Cohen博士的指导，Bruce Cohen博士是McLean医院的前任院长和Frazier研究所的现任主任，Frazier研究所是一个使用临床药理学、MRS、功能性MR和实验室技术研究双相情感障碍的跨学科联盟，同时由McLean医院脑成像中心的Perry Renshaw博士共同指导。Forester博士将通过MRI技术和应用、生物统计学和负责任的研究行为方面的正式培训来提高他的临床技能。拟议的研究计划将使用MRS来研究35名老年双相抑郁症患者和25名年龄匹配的健康对照者的脑部能量代谢测量。符合纳入标准的受试者将在基线时通过结构化的精神病学访谈和神经心理学测试进行临床特征描述，并将在4特斯拉进行质子（1H） MRS研究。双相抑郁症患者将接受拉莫三嗪单药治疗或辅助治疗，为期8周。在8周结束时，两组都将进行第二次4特斯拉的1H MRS扫描。分析对照组和双相障碍患者在治疗前和治疗后脑能量代谢物谷氨酸、谷氨酰胺、n -乙酰天冬氨酸和乳酸的组间差异。公共卫生相关性：双相情感障碍是老年人的一个重要卫生保健问题，它与残疾、功能下降、死亡率和对公共卫生系统的需求增加有关。老年双相抑郁症的治疗是复杂和具有挑战性的，很少有系统的研究可以指导治疗干预。这项研究将检测情绪稳定药物治疗前后与大脑能量代谢相关的生化物质。来自本研究和未来有关老年双相抑郁症的研究的信息可能有助于开发更有效和安全的治疗方法。

DESCRIPTION (provided by applicant): Dr. Forester aims to become an independent investigator in the field of geriatric bipolar disorder using magnetic resonance spectroscopy (MRS) to study biochemical markers of treatment response. Long-term career goals include collaboration with other centers employing MR imaging (MRI) technologies to study geriatric bipolar disorder with a focus on developing safe and effective therapeutic interventions. Dr. Forester will be mentored at McLean Hospital by Dr. Bruce Cohen, past President of McLean Hospital and current Director of the Frazier Institute, an interdisciplinary consortium studying bipolar disorder using clinical pharmacology, MRS, functional MR and laboratory techniques, and co-mentored by Dr. Perry Renshaw, of the McLean Hospital Brain Imaging Center. Dr. Forester will enhance his clinical skills with formal training in MRI techniques and applications, biostatistics and the responsible conduct of research. The proposed research plan will employ MRS to study measures of brain energy metabolism in 35 older adults with bipolar depression and 25 healthy age-matched controls. Subjects meeting inclusion criteria will be clinically characterized at baseline with a structured psychiatric interview and neuropsychological testing and will undergo proton (1H) MRS study at 4 Tesla. Subjects with bipolar depression will then receive open label treatment with lamotrigine as monotherapy or adjunctive therapy for eight weeks. At the end of 8 weeks, both groups will undergo a second 1H MRS scan at 4 Tesla. Group differences in the brain energy metabolites, glutamate, glutamine, N-acetyl aspartate and lactate, among control subjects and subjects with bipolar disorder will be analyzed at baseline and after treatment. PUBLIC HEALTH RELEVANCE: Bipolar disorder is a significant health care issue for elderly individuals, which is associated with disability, functional decline, mortality and increased demands on the public health system. The treatment of bipolar depression in later life is complex and challenging, with little systematic research available to guide therapeutic interventions. This study will examine biochemicals associated with brain energy metabolism before and after treatment with a mood stabilizing medication. Information from this and future related studies of geriatric bipolar depression might help inform the development of more effective and safe treatments.