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: 10208668
• 负责人: VINCENT A MAGNOTTA
• 金额: $ 45.76万
• 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 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10208668
• 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; Modeling; Montgomery and Asberg depression rating scale; Moods; Participant; Patients; Pharmaceutical Preparations; Play; Population; Process; Prosencephalon; Protons; 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; multimodality; network models; neural circuit; neural model; psychiatric symptom; recruit

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.

抽象的 躁郁症（BD）是一种经常毁灭性的精神病，诊断和治疗具有挑战性。 确定这种疾病的基本机制可能为更好的证据提供基础 诊断和治疗技术。在精神病疾病的背景下，我们最近第一次 探索了旋转框架中称为T1松弛的磁共振成像（MRI）策略的实用性 （T1ρ），对脑pH高度敏感。我们测试了BD患者的正式状态，发现 与匹配的对照相比，突出的T1ρ差异。最近，我们还用BD对参与者进行了成像 在沮丧和躁狂的状态下。这些研究表明，最突出的T1ρ的大脑区域 双相情感障碍的变化是小脑，以前已经建议结构有助于BD 但是与前脑结构相比，人们的关注相对较少。 BD的神经解剖模型 在很大程度上忽略了小脑目的地的令人信服的证据，表明小脑已连接很强 致力于情绪控制网络中的大脑区域，该区域已被认为是该疾病的模型。 我们假设小脑活动在调节BD的情绪中起着至关重要的作用，这将在此中进行测试 使用横截面设计和招募BD主题的建议以及 匹配的控件。参与者将接受精神病症状评估和大脑成像。精神病 症状评估将包括蒙哥马利 - 阿斯伯格抑郁评分量表（MADR）和YOUNG 躁狂评级量表（YMRS）。大脑成像将包括定量的全脑T1ρ映射，31p和1H- 小脑vermis的MRS以及扩散成像（DWI）和静止状态fMRI。药物将是 评估并用作分析中的协变量。该数据将用于评估以下目的：目标1）确实 小脑活动在BD中的情绪调节中起着重要作用？我们假设小脑在 在维持正式的情绪状态（即发挥补偿性作用）中的重要作用。我们认为如果 小脑活动使情绪正常，那么当BD参与者是正式和 随着情绪症状的严重程度的增加而减少。替代小脑活动驱动异常的情绪， 然后，在躁狂或沮丧的患者中，它可能是最大的。目标2） Cerebellar Vermis的情绪控制网络与BD中的情绪症状不同吗？我们假设这一点 情绪控制网络的vermis和节点之间的功能连通性会随情绪而变化 状态具有提高正式状态的连通性，并在夸张的情绪中提高连通性 国家（抑郁/躁狂症）。我们还期望在正式状态下的BD参与者会增加 相对于健康控制的连通​​性。这些结果将提供进一步的证据，表明小脑是 发挥补偿性作用以保持情绪。此外，这将支持中性的精致模型 BD病理生理学的基础电路。