Cerebellar metabolism, neural circuits, and symptoms in bipolar disorder

小脑代谢、神经回路和双相情感障碍的症状

• 批准号: 10798452
• 负责人: VINCENT A MAGNOTTA
• 金额: $ 77.28万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-20 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10798452
• 关键词: Address; Anterior; Bipolar Disorder; Bipolar I; Brain imaging; Cerebellar vermis structure; Cerebellum; Corpus striatum structure; Cross-Sectional Studies; Data; Depressed mood; Diagnosis; Disease; Emotional; Exhibits; Face; Failure; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Future; Impulsivity; Individual; Literature; Longitudinal Studies; Manic; Mental Depression; Mental disorders; Metabolic; Metabolism; Moods; Morphology; Participant; Play; Positioning Attribute; Recording of previous events; Research Design; Rest; Role; Severities; Sleep disturbances; Structure; Symptoms; Testing; Therapy trial; Translational Research; Work; anatomic imaging; blood oxygenation level dependent response; brain metabolism; comparison control; depressive symptoms; design; experience; frontal lobe; metabolic imaging; mood regulation; mood symptom; neural circuit; neuroimaging; novel; novel therapeutics; psychiatric symptom; response

Bipolar disorder (BD) is a frequently devastating psychiatric illness that is challenging to diagnose and treat. In our prior work, we have shown that metabolism, function, and morphology of the cerebellum is different in participants with BD as compared to controls. Furthermore, we have observed a relationship between mood and cerebellar metabolism as well as function in a cross-sectional design. These findings support the growing body of literature that the cerebellum is involved with BD. However, there has been a sparsity of studies undertaken that have attempted to follow participants with BD and observe changes in brain metabolism and function associated with fluctuations in mood. We are proposing to conduct a two-year longitudinal study of 170 participants with a diagnosis of BD type I as well as 90 matched controls to study changes in cerebellar metabolism and function associated with mood fluctuations. The participants with BD will receive a brief weekly mood assessment to identify changes in mood where subjects will be assessed using neuroimaging. Brain imaging will include metabolic, functional, and anatomical imaging with the data used address the following aims. Aim 1) Does cerebellar metabolism change with mood in BD? We hypothesize that the cerebellum plays a significant role in maintaining the euthymic mood state (i.e. plays a compensatory role) and when the cerebellum is no longer able to serve this compensatory role depressive or manic mood states develop. To test this hypothesis, we will assess changes in cerebellar metabolism (31P, 1H MRS, and T1ρ) associated with mood changes. Aim 2) Does cerebellar function and connectivity vary with mood in BD? To test the function of the cerebellar vermis, we plan to perform two task-based fMRI studies (backward masking emotional faces and go/no-go). In addition, resting state functional connectivity will allow us to explore connectivity of the cerebellum with the emotional control network. We hypothesize that connectivity between the vermis and nodes of the emotional control network will vary with mood state and expect increased connectivity in the euthymic state and decreased connectivity during exaggerated mood states (depression/mania). Furthermore, we expect that as mood ratings for depression and mania increase subjects with BD will exhibit a greater number of incorrect responses and failure to activate the cerebellum. These results would provide further evidence that the cerebellum is playing a compensatory role to maintain mood. In addition, this study may provide information leading to novel therapy trials in the future.

双相情感障碍(BD)是一种经常具有破坏性的精神疾病，诊断和治疗具有挑战性。在……里面 我们先前的工作表明，小脑的新陈代谢、功能和形态在 与对照组相比，患有BD的参与者。此外，我们还观察到情绪与情绪之间的关系 以及小脑新陈代谢和功能的横断面设计。这些发现支持不断增长的 文献中指出，小脑与BD有关。然而，这方面的研究一直很少。 试图跟踪患有BD的参与者并观察大脑代谢和 与情绪波动有关的功能。我们建议进行一项为期两年的纵向研究 170名被诊断为I型BD的参与者和90名匹配的对照组研究小脑的变化 与情绪波动有关的新陈代谢和功能。患有BD的参与者将每周收到一份简短的 情绪评估，以确定情绪的变化，其中受试者将使用神经成像进行评估。脑区 成像将包括代谢成像、功能成像和解剖成像，使用的数据如下 目标。目的1)BD患者小脑代谢是否随情绪改变？我们假设小脑在 在维持愉悦情绪状态方面的重要作用(即起到补偿作用)，以及当 小脑不再能够起到这种补偿作用，抑郁或躁狂的情绪状态会发展起来。为了测试 在这一假设下，我们将评估小脑代谢的变化(31P，1H MRS和T1ρ)与 心情会变的。目的2)BD患者的小脑功能和连通性是否随情绪变化？测试…的功能 对于小脑蠕虫，我们计划进行两项基于任务的功能磁共振研究(向后掩蔽情绪脸和 去/不去)。此外，休眠状态的功能连接将允许我们探索 小脑与情绪控制网络。我们假设蠕虫和昆虫之间的联系 情绪控制网络的节点将随着情绪状态的不同而变化，并期望在 在夸张的情绪状态(抑郁/躁狂)期间，情绪愉悦状态和连接性降低。此外， 我们预计，随着抑郁和躁狂情绪评分的增加，患有BD的受试者将表现出更大的 错误反应和小脑激活失败的次数。这些结果将进一步提供 有证据表明，小脑在维持情绪方面起着代偿作用。此外，这项研究可能 为未来的新疗法试验提供信息。