Neuroinflammation and Executive Function in Bipolar Disorder: A PET-fMRI Study

双相情感障碍的神经炎症和执行功能：PET-fMRI 研究

• 批准号: 10319012
• 负责人: Amy Peters
• 金额: $ 19.98万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-15 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10319012
• 关键词: Active Biological Transport; Adult; Afferent Pathways; Age; Attention; Attenuated; Autopsy; Basal Ganglia; Behavior; Binding; Bipolar Disorder; Bipolar I; Brain; Brain imaging; Clinical; Cognition; Cognitive; Cognitive deficits; Consultations; Cytokine Receptors; Data; Development; Disinhibition; Encephalitis; Ensure; Executive Dysfunction; Exhibits; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Future; Goals; Imaging Device; Imaging technology; Immune; Immunologic Markers; Immunology; Immunotherapy; Impulsivity; Individual; Inflammation; Inflammatory; Investigational Therapies; Lead; Link; Magnetic Resonance Imaging; Measurement; Measures; Mental Depression; Mentors; Mentorship; Methodology; Mood Disorders; National Institute of Mental Health; Neurobehavioral Manifestations; Neurobiology; Neuroglia; Neuroimmune; Neurons; Organ; Participant; Performance; Peripheral; Positron-Emission Tomography; Prefrontal Cortex; Productivity; Proteins; Psychoneuroimmunology; Radiopharmaceuticals; Research; Research Project Grants; Rest; Role; Scanning; Schizophrenia; Self Destructive Behavior; Specificity; Suicide; Training; Unemployment; Work; brain circuitry; brain dysfunction; career; career development; clinically significant; cognitive performance; cognitive testing; cytokine; density; executive function; experience; follow-up; glial activation; human imaging; imaging study; immune activation; improved; in vivo; indexing; inflammatory marker; innovation; knowledge base; mind control; molecular imaging; multimodality; neural circuit; neuroimaging; neuroimmunology; neuroinflammation; neuroregulation; novel; programs; radioligand; receptor; relating to nervous system; response; statistics; success; tool; translational scientist

Individuals with bipolar disorder (BD) experience severe and persistent difficulties with executive functions, such as inhibitory control. Inhibitory control difficulties in BD could be related to inflammation via its effects on brain functioning. However, direct measurement of brain inflammation markers (i.e. glial activation) in BD is limited and further understanding of how glial activation contributes to inhibitory brain dysfunction in BD is needed. The goal of this proposal is to study the neuroinflammatory basis of inhibitory control and identify novel neuroimmune treatment targets for executive dysfunction in mood disorders. To this end, the candidate proposes: (1) training objectives to establish expertise in the use of simultaneous PET-MRI as a research tool, an interdisciplinary knowledge base in psychoneuroimmunology, and full independence with fMRI methodology, which together will further career development into an expert clinical translational researcher in bipolar disorder; (2) a research objective to examine glial activation as a mechanism of inhibitory control brain dysfunction and cognitive performance in BD; (3) a team of mentors and advisors to ensure the candidate’s success, with expertise in bipolar disorder (Dr. Andrew Nierenberg), multi-modal psychiatric neuroimaging (Dr. Darin Dougherty), molecular imaging and simultaneous PET-fMRI (Dr. Jacob Hooker), psychiatric neuroimmunology (Dr. Beth Stevens), fMRI inhibitory control paradigms (Dr. Scott Langenecker), and neuroimaging statistics (Dr. Mark Vangel). The rationale for the proposed project is that despite evidence for inflammatory alterations in BD, interrogation of brain inflammatory markers in-vivo and their role in executive functioning is limited. Human imaging with novel radiopharmaceuticals to visualize glial activation and its role in inhibitory brain function is needed. The central hypothesis of the proposal is that glial activation adversely impacts frontostriatal brain circuitry and, in turn, inhibitory control in BD. The proposed specific aims are to determine the: (1) difference in glial activation between BD (n = 20) and healthy controls (HC; n = 20); (2) association between glial activation and inhibitory control neural circuitry in BD; (3) association between glial activation and inhibitory control performance on cognitive testing in BD. This proposed research is innovative for examining markers of brain inflammation as a novel mechanism of the understudied burden of executive function in BD using cutting edge simultaneous PET- fMRI technology. The proposed research is significant because it could yield novel neuroimmune treatment targets and crucial pilot data towards the use of PET-fMRI for understanding the unmet clinical problem of inhibitory dysfunction in BD. Overall, this project and training plan will promote the candidate’s career development by facilitating an independent program of program of research at the interface of psychiatric neuroimaging and neuroimmunology. This is a critical first step in furthering the candidate’s career goals to study the neuroinflammatory basis of cognition and to identify novel neuroimmune targets for future experimental therapeutics in mood disorders.

双相情感障碍（BD）的人在执行功能上遇到严重且持续的困难，例如 作为抑制性控制。 BD的抑制控制困难可能与炎症有关其对大脑的影响 功能。但是，BD中直接测量脑感染标记（即神经胶质激活） 需要进一步了解神经胶质激活如何导致BD中抑制性脑功能障碍。这 该建议的目标是研究抑制性控制的神经炎症基础，并识别新的神经免疫性 情绪障碍执行功能障碍的治疗目标。为此，候选提案：（1）培训 目的是建立使用简单PET-MRI作为研究工具的专业知识，跨学科的目标 fMRI方法论的心理肌免疫学和完全独立的知识基础，这将共同 将职业发展进一步发展成为双相情感障碍专业的临床转化研究人员； （2）研究 目的检查神经胶质激活作为抑制性控制脑功能障碍和认知的机制 BD的性能； （3）一组导师和顾问，以确保候选人的成功，并具有专业知识 双相情感障碍（Andrew Nierenberg博士），多模式精神神经影像学（Darin Dougherty博士），分子 成像和同时发生PET-FMRI（Jacob Hooker博士），精神神经免疫学（Beth Stevens博士），fMRI 抑制性控制范例（Scott Langenecker博士）和神经影像统计（Mark Vangel博士）。 拟议项目的理由是，BD炎症改变的任务证据，审问 脑部炎症标记体内及其在执行功能中的作用是有限的。与小说的人类成像 需要放射性药物以可视化神经胶质激活及其在抑制性脑功能中的作用。中央 该提案的假设是，神经胶质激活对额叶脑回路产生不利影响，然后又影响 BD中的抑制控制。提出的特定目的是确定：（1）神经胶质激活的差异 在BD（n = 20）和健康对照之间（HC; n = 20）之间； （2）神经胶质激活与抑制之间的关联 控制BD中的神经回路； （3）胶质激活与抑制性控制性能之间的关联 BD中的认知测试。这项拟议的研究具有创新的，用于检查脑感染的标志物作为一种 使用前沿同时使用PET- FMRI技术。拟议的研究很重要，因为它可以产生新的神经免疫治疗 目标和至关重要的试点数据用于使用PET-FMRI来理解未满足的临床问题 BD中的抑制功能障碍。总体而言，该项目和培训计划将促进候选人的职业 通过支持精神科界面上的独立研究计划的独立计划开发 神经影像学和神经免疫学。这是促进候选人的职业目标的关键第一步 研究认知的神经炎症基础，并确定未来实验的新型神经免疫靶标 情绪障碍的治疗学。