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 双相情感障碍 (BD) 是一种经常造成破坏的精神疾病，诊断和治疗具有挑战性。 确定这种疾病的潜在机制可能为更好的循证医学奠定基础 诊断和治疗技术。最近，我们首次在精神疾病的背景下 探索了称为 T1 弛豫的磁共振成像 (MRI) 策略在旋转框架中的实用性 (T1ρ)，对大脑 pH 值高度敏感。我们对精神正常状态下的 BD 患者进行了测试，发现 与匹配对照相比，T1ρ 差异显着。最近，我们还对参与者进行了 BD 成像 处于抑郁和躁狂状态。这些研究表明，T1ρ 最突出的大脑区域 双相情感障碍的变化是小脑，之前曾有人认为该结构会导致双相情感障碍 但与前脑结构相比，受到的关注相对较少。 BD 的神经解剖模型 尽管有令人信服的证据表明小脑与小脑紧密相连，但在很大程度上忽视了小脑 涉及情绪控制网络的大脑区域已被提出作为该疾病的模型。 我们假设小脑活动在 BD 患者的情绪调节中发挥着关键作用，这将在本研究中进行测试。 使用横断面设计并招募跨情绪谱系的 BD 受试者的提案以及 匹配的控件。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) 和杨 躁狂评定量表（YMRS）。脑成像将包括定量全脑 T1ρ 映射、31P- 和 1H- 小脑蚓部的 MRS，以及弥散成像 (DWI) 和静息态功能磁共振成像 (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标： 目标 1) 是否 小脑活动在 BD 患者的情绪调节中发挥重要作用？我们假设小脑起着 在维持正常情绪状态方面发挥重要作用（即发挥补偿作用）。我们推断如果 小脑活动使情绪正常化，那么当 BD 参与者情绪正常且 随着情绪症状严重程度的增加而减少。或者，如果小脑活动导致情绪异常， 那么对于躁狂或抑郁的患者来说，这种情况可能最为严重。目标 2) 的连通性 小脑蚓部的情绪控制网络与 BD 的情绪症状有何不同？我们假设 蚓部和情绪控制网络节点之间的功能连接会随着情绪而变化 情绪正常时连通性增加，情绪亢奋时连通性降低的状态 状态（抑郁/躁狂）。我们还预计处于正常状态的 BD 参与者将表现出增加 与健康对照相关的连接性。这些结果将进一步证明小脑是 起到维持情绪的补偿作用。此外，这将支持神经网络的精细模型 BD 病理生理学的基础电路。