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）是一种常见的慢性精神疾病，诊断和治疗具有挑战性。 我们之前的工作表明，小脑的新陈代谢、功能和形态在不同方面是不同的 BD 参与者与对照组相比此外，我们还观察到情绪之间的关系。 和小脑代谢以及横截面设计中的功能这些发现支持了不断增长的结果。 大量文献表明小脑与双相情感障碍有关，但相关研究却很少。 尝试跟踪 BD 参与者并观察大脑代谢的变化和 我们建议进行一项为期两年的纵向研究。 170 名诊断为 I 型 BD 的参与者以及 90 名匹配的对照者来研究小脑的变化 患有 BD 的参与者将每周接受一次简短的与情绪波动相关的新陈代谢和功能的评估。 情绪评估，以识别情绪变化，并使用神经影像学对受试者进行评估。 成像将包括代谢、功能和解剖成像，所使用的数据可解决以下问题 目标 1) 小脑代谢会随着 BD 的情绪而变化吗？ 在维持正常情绪状态（即发挥补偿作用）方面发挥着重要作用，并且当 小脑不再能够发挥这种代偿作用，以测试抑郁或躁狂情绪状态的发展。 根据这一假设，我们将评估与以下因素相关的小脑代谢（31P、1H MRS 和 T1ρ）的变化 目标 2) BD 中小脑功能和连接性是否随情绪变化？ 小脑蚓部，我们计划进行两项基于任务的功能磁共振成像研究（向后掩盖情绪面孔和 此外，静息状态功能连接将使我们能够探索神经网络的连接性。 我们勇敢地面对小脑与情绪控制网络之间的连接。 情绪控制网络的节点会随着情绪状态而变化，并期望情绪控制网络的连接性增加 情绪正常状态和过度情绪状态（抑郁/躁狂）期间的连通性降低。 我们预计，随着抑郁症和躁狂症情绪评级的增加，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数量这些结果将提供进一步的信息。 此外，这项研究还表明小脑在维持情绪方面发挥着代偿作用。 提供未来新疗法试验的信息。