Structural and Functional Brain Aging in Bipolar Disorder

双相情感障碍中的结构和功能性脑老化

• 批准号: 8583343
• 负责人: LISA T EYLER
• 金额: $ 31.54万
• 依托单位: VETERANS MEDICAL RESEARCH FDN/SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8583343
• 关键词: Accounting; Address; Adolescent; Adult; Affect; Age; Aging; Anisotropy; Anxiety Disorders; Biological; Bipolar Disorder; Bipolar I; Blood Vessels; Brain; Brain Pathology; Brain imaging; Brain region; Caring; Clinical; Clinical Research; Cognition; Cognitive; Cognitive aging; Communication; Complex; Cross-Sectional Studies; Disease; Elderly; Exposure to; Fiber; Future; General Population; Genetic; Image; Imaging Techniques; Individual; Intervention; Investigation; Knowledge; Lead; Link; Lithium; Longevity; Longitudinal Studies; Magnetic Resonance; Magnetic Resonance Imaging; Manic; Measurement; Measures; Mediator of activation protein; Mental disorders; Mentally Ill Persons; Mood Disorders; Moods; National Institute of Mental Health; Nature; Neurobehavioral Manifestations; Neurobiology; Neurosciences; Participant; Pathology; Pathway interactions; Patients; Performance; Perfusion; Pharmaceutical Preparations; Play; Population; Prefrontal Cortex; Psyche structure; Recording of previous events; Relative (related person); Research; Research Personnel; Rest; Role; Severities; Short-Term Memory; Signal Pathway; Signal Transduction; Staging; Structure; Subgroup; Substance Addiction; Substance abuse problem; System; Technology; Thick; Time; age difference; age effect; age related; aged; aging brain; blood oxygenation level dependent response; clinical Diagnosis; depressive symptoms; design; effective intervention; executive function; experience; functional decline; functional outcomes; gray matter; healthy aging; improved; neural circuit; normal aging; older patient; prevent; psychotic symptoms; public health relevance; response; therapy design; white matter; young adult

DESCRIPTION (provided by applicant): Bipolar disorder is a disabling and costly mental illness. The number of elderly mentally ill individuals will increase rapidly in the coming decades, yet there has been little research focused on geriatric bipolar patients. In particular, little is known about changes in brain structure and function due to aging that may underlie worsening cognition. NIMH has recognized this unfortunate gap, and PA-07-077 calls for "new research...aimed at delineating the neural circuitry...involved in late-life mood and anxiety disorders." Combining clinical and neuroscience expertise and cutting-edge technologies, the proposed study, led by a new investigator, aims to (1) investigate age-related differences in the structure, function, and connectivity of the prefrontal cortex (PFC) in bipolar disorder and whether these differences are greater than would be expected due to normal age-related changes, (2) examine whether gray and white matter structural integrity serve as possible mediators of the relationship between age and PFC function and functional connectivity, and (3) examine whether PFC function and functional connectivity serve as possible mediators of the relationship between age and cognitive performance. Important secondary analyses will examine similar questions regarding measures of chronicity of bipolar illness and illness course, such as duration since first episode, number of manic and depressive episodes, and cumulative exposure to psychotropic medications. PFC structural and functional deficits are recognized features of bipolar pathology and may be related to biological alterations in neurotrophic and cell signaling pathways. Some studies have found that structural deficits worsen with age among bipolar patients to a greater degree than expected in normal aging, but no study has yet combined measures of PFC gray matter size, white matter integrity and organization, resting perfusion, and functional brain response and connectivity in a single investigation of brain changes across the lifespan in bipolar disorder and healthy individuals. Our study is also designed to examine how age-associated brain measures relate to one another and to cognitive performance. We will use a cross-sectional design to study 85 patients with adolescent- or young-adult-onset Bipolar I disorder and 85 healthy individuals ranging in age from 30 to 79 years. Patients will be stably medicated, not experiencing a mood episode or significant mood or psychotic symptoms, and free of other Axis I disorders including current or recent substance abuse or dependence. Participants will be assessed for diagnosis and clinical history, current symptoms, cognitive performance, and brain structure and function as measured by magnetic resonance imaging. PFC gray matter thickness, white matter organization in tracts that connect with the PFC, resting perfusion and functional response of the prefrontal cortex and connected regions during working memory tasks will be measured. Results of this study will help characterize the course of brain pathology in bipolar disorder and enable future longitudinal investigations using the best measures and focusing on the most likely time period for change.

描述（由申请人提供）：躁郁症是一种残疾和昂贵的精神疾病。在未来几十年中，老年人精神病患者的数量将迅速增加，但很少有研究重点是老年双极患者。特别是，由于衰老可能导致认知恶化的衰老而导致的大脑结构和功能的变化知之甚少。 NIMH认识到了这一不幸的差距，PA-07-077呼吁“新研究……旨在描述涉及晚期情绪和焦虑症的神经循环……”。由新研究者领导的拟议研究结合了临床和神经科学专业知识和尖端技术，旨在（1）研究双相情感障碍和前额叶皮层（PFC）的结构，功能和连通性与年龄相关的差异这些差异是否大于正常与年龄相关的变化，（2）检查灰色和白质结构完整性是否可以作为年龄与PFC功能与功能连接性之间关系的可能介体，以及（3）检查PFC功能和功能连通性是年龄和认知表现之间关系的可能介体。重要的次要分析将研究有关双相疾病和疾病病程的慢性措施的类似问题，例如自第一事件以来的持续时间，躁狂和抑郁发作的数量以及累积暴露于精神药物。 PFC结构和功能缺陷是双极病理的公认特征，可能与神经营养和细胞信号通路的生物学改变有关。一些研究发现，双极患者的结构缺陷随着正常衰老而预期的高度随着年龄的增长而恶化，但是尚未将PFC灰质大小，白质完整性和组织，静息灌注以及功能性脑反应以及功能性脑反应和功能性脑反应和功能性的研究结合在一起在对躁郁症和健康个体中整个寿命的单一研究中，连通性的连通性。我们的研究还旨在检查与年龄相关的大脑测量与彼此与认知表现的关系。我们将使用横截面设计来研究85例青少年或年轻人发作双相情感障碍的患者，以及30至79岁的85名健康个体。患者将被稳定治疗，不会出现情绪发作，情绪或精神病性症状，并且没有其他轴I疾病，包括当前或最近的药物滥用或依赖性。将评估参与者的诊断和临床病史，当前症状，认知表现以及大脑结构以及通过磁共振成像衡量的功能。 PFC灰质厚度，与PFC连接的区域中的白色物质组织，将测量前额叶皮层和连接区域的静止灌注和功能响应。这项研究的结果将有助于表征躁郁症中脑病理学的进程，并使用最佳措施进行未来的纵向研究，并专注于最可能的变化时期。

项目成果

Overlapping prefrontal systems involved in cognitive and emotional processing in euthymic bipolar disorder and following sleep deprivation: a review of functional neuroimaging studies.

• DOI: 10.1016/j.cpr.2012.07.003
• 发表时间: 2012-11
• 期刊: CLINICAL PSYCHOLOGY REVIEW
• 影响因子: 12.8
• 作者: McKenna, Benjamin S.;Eyler, Lisa T.
• 通讯作者: Eyler, Lisa T.

Disruptions in resting state functional connectivity in euthymic bipolar patients with insomnia symptoms.

有失眠症状的正常双相情感障碍患者静息态功能连接中断。

• DOI: 10.1016/j.pscychresns.2018.03.005
• 发表时间: 2018
• 期刊: Psychiatry research. Neuroimaging
• 作者: Yoon,Ho-Kyoung;Dev,SheenaI;Sutherland,AshleyN;Eyler,LisaT
• 通讯作者: Eyler,LisaT

The interplay of daily affect and impulsivity measured by mobile surveys in bipolar disorder.

• DOI: 10.1186/s40345-022-00270-8
• 发表时间: 2022-10-31
• 期刊: INTERNATIONAL JOURNAL OF BIPOLAR DISORDERS
• 影响因子: 4
• 作者: Titone, Madison K.;Depp, Colin;Klaus, Federica;Carrasco, Jessica;Young, Jared W.;Eyler, Lisa T.
• 通讯作者: Eyler, Lisa T.