Cerebellar metabolism, neural circuits, and symptoms in bipolar disorder

双相情感障碍（BD）是一种经常具有破坏性的精神疾病，其诊断和治疗具有挑战性。 我们先前的工作表明，小脑的代谢、功能和形态在不同的年龄段是不同的。 BD患者与对照组相比。此外，我们还观察到情绪与 和小脑的代谢以及功能。这些发现支持了不断增长的 小脑与BD有关的文献。然而，研究很少， 他们试图跟踪BD参与者并观察大脑代谢的变化， 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BD I型的参与者以及90名匹配的对照者研究小脑的变化。 代谢和功能与情绪波动有关。BD的参与者每周将收到一份简短的 情绪评估，以确定情绪的变化，其中将使用神经成像对受试者进行评估。大脑 成像将包括代谢、功能和解剖成像，所用数据用于以下目的 目标。目的1）BD患者小脑代谢是否随情绪改变而改变？我们假设小脑 在维持正常情绪状态中起重要作用（即起补偿作用）， 小脑不再能够起到这种补偿作用，抑郁或躁狂情绪状态发展。测试 根据这一假设，我们将评估与以下因素相关的小脑代谢（31 P，1H MRS和T1ρ）的变化： 情绪变化。目的2）BD患者小脑的功能和连通性是否随情绪变化而变化？测试的功能 小脑蚓部，我们计划进行两个基于任务的功能磁共振成像研究（向后掩蔽情绪面孔， 通过/不通过）。此外，静息状态下的功能连接将使我们能够探索 小脑的情绪控制网络。我们假设蚓部和 情绪控制网络的节点将随着情绪状态而变化，并期望在情绪控制网络中增加连接。 情绪正常状态和夸大情绪状态（抑郁/躁狂）期间的连接性降低。此外，委员会认为， 我们预计，随着抑郁和躁狂情绪评分的增加，BD患者将表现出更大的 错误的反应次数和小脑激活失败。这些结果将进一步提供 小脑在维持情绪方面起着补偿作用。此外，这项研究可能 为未来的新疗法试验提供信息。

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.