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: 9379194
• 负责人: VINCENT A MAGNOTTA
• 金额: $ 59.06万
• 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 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9379194
• 关键词: Address; Affect; Area; Attention; Bipolar Disorder; Brain; Brain imaging; Brain region; Cerebellar vermis structure; Cerebellum; Corpus striatum structure; Data; Depressed mood; Diagnosis; Diagnostic; Diffusion; Diffusion Magnetic Resonance Imaging; Disease model; Emotional; Exhibits; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Image; Literature; Magnetic Resonance Imaging; Manic; Measures; Mental Depression; Mental disorders; Metabolism; Modality; Modeling; Montgomery and Asberg depression rating scale; Moods; Participant; Patients; Pharmaceutical Preparations; Play; Population; Process; Prosencephalon; Protons; Recruitment Activity; Relaxation; Rest; Role; Schizophrenia; Severities; Signal Transduction; Specificity; Structure; Symptoms; Techniques; Testing; Therapeutic; Time; bipolar spectrum; brain metabolism; design; evidence base; imaging modality; insight; mood regulation; mood symptom; network models; neural circuit; neural model; psychiatric symptom

Abstract Bipolar disorder (BD) is a frequently devastating psychiatric illness that is challenging to diagnose and treat. Identifying the underlying mechanisms of this illness may provide a foundation for better evidence-based diagnostic and therapeutic techniques. For the first time in the context of psychiatric illness, we recently explored the utility of a magnetic resonance imaging (MRI) strategy called T1 relaxation in the rotating frame (T1ρ), which is highly sensitive to brain pH. We tested patients with BD in the euthymic state and found prominent T1ρ differences compared to matched controls. More recently, we also imaged participants with BD in depressed and manic states. These studies suggest that the brain area with the most prominent T1ρ changes in bipolar disorder is the cerebellum, a structure has been previously suggested to contribute to BD but has received relatively little attention compared to forebrain structures. Neuroanatomical models of BD have largely overlooked the cerebellum despite compelling evidence that the cerebellum is strongly connected to brain regions involved in the emotional control network that has been put forth as a model of the disorder. We hypothesize that cerebellar activity plays a critical role in regulating mood in BD, which will be tested in this proposal using a cross-sectional design and recruiting BD subjects across the mood spectrum as well as matched controls. Participants will undergo psychiatric symptom assessment and brain imaging. Psychiatric symptom assessments will include, the Montgomery-Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS). Brain imaging will include quantitative whole-brain T1ρ mapping, 31P- and 1H- MRS of the cerebellar vermis, as well as diffusion imaging (DWI) and resting state fMRI. Medications will be assessed and used as covariates in analyses. This data will be used to assess the following aims: Aim 1) Does cerebellar activity play a significant role in mood regulation in BD? We hypothesize that the cerebellum plays a significant role in maintaining a euthymic mood state (i.e., plays a compensatory role). We reason that if cerebellar activity normalizes mood, then its activity should be greatest when BD participants are euthymic and decrease with increasing mood symptom severity. Alternatively, if cerebellar activity drives abnormal moods, then it is likely to be greatest in patients who are manic or depressed. Aim 2) Does connectivity of the cerebellar vermis with the emotional control network differ with mood symptoms in BD? We hypothesize that functional connectivity between the vermis and nodes of the emotional control network will vary with mood state with increased connectivity in the euthymic state and decreased connectivity during exaggerated mood states (depression/mania). We also expect that BD participants in the euthymic state will exhibit increased connectivity relative to healthy controls. These results would provide further evidence that the cerebellum is playing a compensatory role to maintain mood. In addition, this would support a refined model of the neural circuits underlying the pathophysiology of BD.

摘要 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。 确定这种疾病的潜在机制可能会为更好的循证研究奠定基础 诊断和治疗技术。在精神疾病的背景下，我们最近第一次 探索了名为T1松弛的磁共振成像(MRI)策略在旋转坐标系中的应用 (T1ρ)，对脑pH高度敏感。我们测试了处于愉悦状态的BD患者，发现 与匹配对照组相比，T1ρ差异显著。最近，我们还为参与者拍摄了患有BD的图像 处于抑郁和躁狂状态。这些研究表明，T1ρ最显著的大脑区域 双相情感障碍的变化是小脑，这一结构此前已被认为与BD有关 但与前脑结构相比，它受到的关注相对较少。BD的神经解剖学模型 在很大程度上忽略了小脑，尽管有令人信服的证据表明小脑与 与情绪控制网络相关的大脑区域，情绪控制网络已被提出为这种疾病的模型。 我们假设，小脑活动在调节BD患者的情绪方面起着关键作用，这一点将在这里得到验证 建议采用横断面设计，招募不同情绪谱的BD受试者以及 配对的对照组。参与者将接受精神症状评估和脑成像。精神科 症状评估将包括蒙哥马利-阿斯伯格抑郁量表(MADRS)和Young 躁狂评定量表(YMRS)。脑成像将包括定量的全脑T1ρ图，31P和1H图 小脑虫的磁共振波谱，以及弥散成像(DWI)和静息功能磁共振成像。药物将会是 在分析中作为协变量进行评估和使用。这些数据将用于评估以下目标：Aim 1)是否 小脑活动在BD的情绪调节中起着重要作用？我们假设小脑在大脑中扮演着 在维持愉悦的情绪状态方面起着重要作用(即起到代偿作用)。我们推断，如果 小脑活动使情绪正常化，那么当BD参与者心情愉悦和 随着情绪症状严重程度的增加而减少。或者，如果小脑活动导致异常情绪， 那么它很可能在躁狂或抑郁的患者中表现得最好。目标2)连接 有情绪控制网络的小脑蠕虫与BD的情绪症状有什么不同？我们假设 蚯蚓和情绪控制网络节点之间的功能连接将随着情绪的变化而变化 心情愉悦时连接性增强，而情绪夸张时连接性降低的状态 国家(抑郁/躁狂)。我们还预计处于愉悦状态的BD参与者将表现出更多 相对于健康对照的连接性。这些结果将提供进一步的证据，证明小脑 起到了维持情绪的补偿作用。此外，这将支持神经的改进模型。 BD的病理生理学基础电路。