Longitudinal Imaging Studies in Bipolar Disorder

项目摘要 候选人要求支持一个为期五年的培训和研究计划，以更好地了解 双相情感障碍患者的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本经验之上。 神经科学研究和临床精神病学在姆克林医院和 贝斯-以色列女执事医疗中心他的培训计划包括：1）培训在磁的应用 共振光谱（MRS）用于神经递质活性和脑代谢的体内研究2）训练 在使用功能性磁共振成像（fMRI）检查神经网络活动方面， 设计和执行以患者为导向的调查，以及4）培训负责任的行为 research. 双相情感障碍的一个标志性特征是它本质上是偶发性的， 向病理状态的转变和随后向正常心境的恢复或向另一种状态的转变。有 对引起情绪状态不稳定的生物学或使情绪状态不稳定的过程知之甚少。 这些国家是暂时的。本研究提出双相情感障碍的病理生理学特征为：1） 参与情感调节的脑区之间的原始异常功能耦合，以及2） 神经传递的代偿性变化。这些变化引发了一系列的力量， 大脑功能不稳定。 候选人的研究计划旨在：1）探索大脑网络活动与 双相情感障碍的情绪状态和2）测试情绪状态转换的模型，提出了一个平衡， 兴奋性和抑制性神经传递，可以补偿大脑网络中与特征相关的改变 连通性。 这项研究提出通过观察大脑网络活动以及 测量体内神经递质和神经元活动的标记物。这些实验将在 双相情感障碍受试者的一个队列纵向经历躁狂和心境正常的临床状态。在 这样做，这项研究旨在尽量减少许多实质性的混乱，研究这种疾病，包括疾病 异质性、诊断不稳定性和药物作用。 这项研究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衰弱的疾病，目前的治疗方法只有部分有效。一个 了解状态之间转换的生理基础将允许更好地开发 干预措施，以防止病理转换为躁狂症或抑郁症。

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.