Longitudinal Imaging Studies in Bipolar Disorder

双相情感障碍的纵向影像研究

• 批准号: 8785136
• 负责人: Roscoe O. Brady
• 金额: $ 17.67万
• 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/8785136
• 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; Metabolism; 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; Relative (related person); 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; emotion regulation; experience; frontal lobe; gamma-Aminobutyric Acid; hypomania; in vivo; indexing; longitudinal design; multidisciplinary; neural circuit; 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，以更好地了解双相情感障碍如何改变脑生物化学和神经活动。 在拟议的培训计划中，候选人将根据他以前在基本神经科学研究和临床精神病学方面的经验来实现在麦克莱恩医院和贝丝 - 以色列执事医疗中心进行多学科项目。他的培训计划包括：1）在应用磁共振光谱（MRS）对神经递质活性和脑代谢的体内研究中的培训2）在使用功能磁共振成像（fMRI）中训练以检查神经网络活动以检查神经网络活动3）在设计和执行患者方便研究和4）培训研究中的培训。 双相情感障碍的标志性特征是，它本质上是偶发性的，似乎是自发过渡到病理状态，并随后重新归还了安特米亚或过渡到另一个状态。人们对生物学几乎没有理解，从而导致情绪状态的这种不稳定或使这些状态暂时的过程。这项研究提出，躁郁症的病理生理特征是：1）与情感调节有关的大脑区域之间的原始异常功能耦合，以及2）神经传递的补偿性变化。这些变化在运动中引起了一系列在大脑功能中产生不稳定性的力。 候选人的研究计划试图：1）探索双相情感障碍中大脑网络活动与情绪状态之间的关系，2）测试一种情绪状态转换模型，该模型提出了兴奋性和抑制性神经传递平衡，可以弥补大脑网络连接性的性状相关变化。 这项研究建议通过观察脑网络活性以及测量体内神经元活性的神经递质和标记来解决这一假设。这些实验将在单个受试者中进行双相情感障碍的临床状态。在此过程中，这项研究旨在最大程度地减少研究这种疾病（包括疾病异质性，诊断不稳定和药物效应）的许多实质性混杂。 这项研究的更广泛的目的是了解躁郁症状态转换的生理学。这种疾病是一种常见且令人衰弱的疾病，目前的治疗只是部分有效。对国家之间过渡的生理基础的理解将允许发展更好的干预措施，以防止病理切换到躁狂或抑郁症。