Longitudinal Imaging Studies in Bipolar Disorder

双相情感障碍的纵向影像研究

• 批准号: 8957410
• 负责人: Roscoe O. Brady
• 金额: $ 17.64万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-12-11 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8957410
• 关键词: Address; Affect; Affective; Anterior; Behavioral; Biochemistry; Biological Neural Networks; Biology; Bipolar Disorder; Brain; Brain Chemistry; Brain region; Chronic; Clinical; Clinical Research; Coupling; Data; Development; Diagnosis; Diagnostic; Disease; Dorsal; Emotional; Emotions; Equilibrium; Figs - dietary; Functional Magnetic Resonance Imaging; Functional disorder; Glutamates; Glutamine; Health; Heterogeneity; Homeostasis; Hospitals; Image; Intervention; Investigation; Israel; K-Series Research Career Programs; Literature; Magnetic Resonance Spectroscopy; Manic; Measures; Medial; Medical center; Mental Depression; Metabolic; Metabolic Marker; Modeling; Moods; Motion; N-acetylaspartate; Nature; Neuroanatomy; Neurons; Neurosciences; Neurosciences Research; Neurotransmitters; Output; Pathology; Perception; Pharmaceutical Preparations; Physiological; Physiology; Population; Process; Protons; Psychiatry; Recurrence; Regulation; Research; Research Personnel; Research Training; Rest; Series; Structure; System; Testing; Theoretical model; Time; Training; Training Programs; base; brain metabolism; cingulate cortex; cognitive change; cohort; design; disease heterogeneity; emotion regulation; experience; frontal lobe; gamma-Aminobutyric Acid; hypomania; in vivo; indexing; longitudinal design; multidisciplinary; neural circuit; neuronal metabolism; neurotransmission; patient oriented; prevent; relating to nervous system; research study; responsible research conduct; trait; treatment effect

DESCRIPTION (provided by applicant): 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 buid 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 th 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.

描述（由申请人提供）：候选人请求支持为期五年的培训和研究计划，以更好地了解躁郁症患者的大脑生物化学和神经活动如何改变。 在拟议的培训计划中，候选人将利用他之前在基础神经科学研究和临床精神病学方面的经验，在麦克莱恩医院和贝斯以色列女执事医疗中心执行一个多学科项目。他的培训计划包括： 1) 应用磁共振波谱 (MRS) 进行神经递质活动和大脑代谢体内研究的培训 2) 使用功能磁共振成像 (fMRI) 检查神经网络活动的培训 3) 培训设计和执行以患者为导向的调查，以及 4) 负责任地进行研究的培训。 双相情感障碍的一个标志性特征是，它本质上是偶发性的，似乎是自发转变为病理状态，随后恢复到正常状态或转变为另一种状态。人们对引起情绪状态不稳定的生物学原理或使这些状态短暂的过程知之甚少。本研究提出双相情感障碍的病理生理学特征为：1）参与情感调节的大脑区域之间原始的异常功能耦合，2）神经传递的代偿性变化。这些改变引发了一系列的力量，导致大脑功能不稳定。 候选人的研究计划旨在：1）探索双相情感障碍的大脑网络活动与情绪状态之间的关系，2）测试情绪状态转换模型，该模型提出了兴奋性和抑制性神经传递的平衡，可以补偿大脑中与特质相关的改变网络连接。 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标记物来解决这一假设。这些实验将在一组患有双相情感障碍的受试者中纵向进行躁狂和正常的临床状态。在此过程中，本研究旨在最大限度地减少研究这种疾病的许多实质性混淆，包括疾病异质性、诊断不稳定性和药物效应。 这项研究更广泛的目标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且使人衰弱的疾病，目前的治疗仅部分有效。了解状态之间转变的生理基础将有助于制定更好的干预措施，以防止病理性转变为躁狂或抑郁。