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: 7793182
• 负责人: LISA T EYLER
• 金额: $ 31.86万
• 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 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7793182
• 关键词: Accounting; Address; Adolescent; Adult; Affect; Age; Aging; Anisotropy; Anxiety Disorders; Biological; Bipolar Disorder; Blood Vessels; Brain; Brain Pathology; Brain imaging; Brain region; Caring; Clinical; Clinical Research; Cognition; Cognitive; Cognitive aging; Communication; Complex; Cross-Sectional Studies; Dependence; Disease; Elderly; Exposure to; Fiber; Future; General Population; Genetic; Gray unit of radiation dose; 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; 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 abuse problem; Symptoms; 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; 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. PUBLIC HEALTH RELEVANCE: Little is known about how the brains of adults with bipolar disorder may change during aging and whether these changes are different from those seen in healthy aging. We will study the relationship of age to magnetic resonance imaging measures of prefrontal cortex gray matter thickness, white matter organization and integrity, and functional response during cognitive activities among groups of stable bipolar patients and healthy individuals. We will also examine how the brain measures relate to one another and to cognitive ability and examine how other chronicity measures may relate to age differences in the bipolar group. The results of this study will improve our knowledge about how aging influences brain abnormalities in bipolar disorder and may suggest new treatments designed to prevent negative effects and capitalize on any positive changes.

描述（由申请人提供）：双相情感障碍是一种致残和昂贵的精神疾病。老年精神病患者的数量将在未来几十年迅速增加，但很少有研究集中在老年双相情感障碍患者。特别是，由于衰老而导致的大脑结构和功能的变化可能是认知能力恶化的基础，对此我们知之甚少。NIMH已经认识到这一不幸的差距，PA-07-077呼吁“新的研究……旨在描绘神经回路…与老年情绪和焦虑症有关。”结合临床和神经科学专业知识和尖端技术，这项由一位新研究者领导的拟议研究旨在(1)调查双相情感障碍患者前额叶皮质（PFC）结构、功能和连通性的年龄相关差异，以及这些差异是否比正常年龄相关变化所预期的要大；(2)研究灰质和白质结构完整性是否可能是年龄与PFC功能和功能连接之间关系的中介；(3)研究PFC功能和功能连接是否可能是年龄与认知表现之间关系的中介。重要的二次分析将检验关于双相情感障碍的慢性测量和病程的类似问题，如自首次发作以来的持续时间，躁狂和抑郁发作的次数，以及对精神药物的累积暴露。PFC结构和功能缺陷是公认的双相病理学特征，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，在双相情感障碍患者中，结构缺陷随着年龄的增长而恶化，其程度比正常衰老时预期的要大，但尚未有研究将PFC灰质大小、白质完整性和组织、静息灌注、功能性脑反应和连通性的测量结合起来，对双相情感障碍患者和健康个体的整个生命周期的大脑变化进行单一调查。我们的研究还旨在研究与年龄相关的大脑测量是如何相互关联的，以及与认知表现的关系。我们将采用横断面设计来研究85名青少年或青年型双相I型患者和85名年龄在30至79岁之间的健康个体。患者应稳定用药，无情绪发作或显著情绪或精神病症状，无其他I轴障碍，包括当前或最近的药物滥用或依赖。参与者将被评估诊断和临床病史、当前症状、认知表现以及通过磁共振成像测量的大脑结构和功能。在工作记忆任务中测量前额皮质灰质厚度、连接前额皮质的脑束白质组织、静息灌注和前额皮质及其连接区域的功能反应。这项研究的结果将有助于描述双相情感障碍的脑部病理过程，并使未来的纵向调查能够使用最佳的测量方法，并关注最可能发生变化的时间段。