Longitudinal Imaging Studies in Bipolar Disorder

项目摘要 候选人请求支持一项为期五年的培训和研究计划，以更好地了解 双相情感障碍的大脑生化和神经活动是如何改变的。 在拟议的培训计划中，候选人将建立在他以前的基础上的经验 神经科学研究和临床精神病学在麦克莱恩医院和 贝丝-以色列女执事医疗中心。他的培训计划包括：1)磁力应用方面的培训 磁共振波谱(MRS)在体内研究神经递质活性和脑代谢2)训练 在使用功能磁共振成像(FMRI)检查神经网络活动方面3)培训 设计和实施以病人为中心的调查和4)负责任的行为培训 研究。 双相情感障碍的一个显著特征是它在本质上是间歇性的，看起来是自发的。 转换到病理状态，然后恢复到欣快感或转换到另一种状态。的确有 对导致情绪状态不稳定的生物学因素或导致情绪不稳定的过程知之甚少 这些状态是暂时的。本研究提出双相情感障碍的病理生理学特征为：1) 参与情绪调节的脑区之间原有的异常功能耦合，2) 神经传递的代偿性变化。这些变化引发了一系列的力量，产生了 大脑功能不稳定。 候选人的研究计划寻求：1)探索大脑网络活动和 双相情感障碍的情绪状态和2)测试情绪状态转换模型，该模型提出了一种平衡 兴奋性和抑制性神经传递可以补偿脑网络中与特征相关的改变 连通性。 这项研究建议通过观察大脑网络活动以及 在活体内测量神经递质和神经元活动的标志物。这些实验将在 通过躁狂症和欣快症的临床状态纵向研究双相情感障碍患者的单一队列。在……里面 这样做，这项研究试图最大限度地减少研究包括疾病在内的这种疾病的许多实质性混淆。 异质性、诊断不稳定性和药物效应。 这项研究的更广泛的目的是了解双相情感障碍状态转换的生理学。 这种疾病是一种常见的、使人虚弱的疾病，目前的治疗方法只有部分有效。一个 对状态间转换的生理基础的了解将有助于更好地开发 防止病理性转变为躁狂或抑郁的干预措施。

Project Summary The candidate requests support for a five year program of training and research to better understand how brain biochemistry and neural activity are altered in bipolar disorder. In the proposed training program, the candidate will build upon his previous experience in basic neuroscience research and clinical psychiatry to perform a multidisciplinary project at McLean Hospital and the Beth-Israel Deaconess Medical Center. His training plan includes: 1) training in the application of Magnetic Resonance Spectroscopy (MRS) to in vivo studies of neurotransmitter activity and brain metabolism 2) training in the use of functional Magnetic Resonance Imaging (fMRI) to examine neural network activity 3) training in the design and execution of patient oriented investigation and 4) training in the responsible conduct of research. A hallmark feature of bipolar disorder is that it is episodic in nature with what appear to be spontaneous transitions to pathological states and subsequent reversion to euthymia or transition to another state. There is little understood about the biology that gives rise to this instability in mood state or the processes that make these states transitory. This study proposes that the pathophysiology of bipolar disorder is characterized by: 1) original abnormal functional coupling between the brain regions involved in affective regulation, and 2) compensatory changes in neurotransmission. These alterations set in motion a series of forces that generate instability in brain function. The candidate's research plan seeks to: 1) explore the relationship between brain network activity and mood state in bipolar disorder and 2) test a model of mood state switching that proposes a balance of excitatory and inhibitory neurotransmission that can compensate for trait related alterations in brain network connectivity. This study proposes to address this hypothesis by observing brain network activity as well as measuring neurotransmitters and markers of neuronal activity in vivo. These experiments will be performed in a single cohort of subjects with bipolar disorder longitudinally through clinical states of mania and euthymia. In doing so, this study seeks to minimize many substantial confounds of studying this disorder including disease heterogeneity, diagnostic instability, and medication effects. The broader aim of this research is to understand the physiology of state switching in bipolar disorder. This disorder is a common and debilitating illness and current treatments are only partially effective. An understanding of the physiologic basis of transitions between states will allow the development of better interventions to prevent pathological switching to mania or depression.