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: 8367831
• 负责人: LISA T EYLER
• 金额: $ 30.28万
• 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/8367831
• 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; 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; 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.

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患者。特别是，人们对大脑结构和功能因衰老而发生的变化知之甚少，而这些变化可能是认知能力恶化的基础。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晚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，这项由新研究人员领导的拟议研究旨在（1）调查双相情感障碍患者前额叶皮层（PFC）结构，功能和连接性的年龄相关差异，以及这些差异是否大于正常年龄相关变化的预期，（2）检查灰质和白色物质结构完整性是否作为年龄与PFC功能和功能连接之间关系的可能中介物;（3）检查PFC功能和功能连接是否作为年龄与认知表现之间关系的可能中介物。重要的次要分析将检查关于双相情感障碍慢性化和病程测量的类似问题，例如自首次发作以来的持续时间、躁狂和抑郁发作次数以及精神药物的累积暴露。PFC结构和功能缺陷是双相情感障碍的公认特征，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，双相情感障碍患者的结构性缺陷随着年龄的增长而恶化，其程度比正常衰老的预期程度更大，但还没有研究将PFC灰质大小、白色物质完整性和组织、静息灌注以及功能性脑反应和连接性的测量结合起来，对双相情感障碍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措施如何相互关联以及与认知表现的关系。我们将采用横断面设计，研究85例青少年或非成人发作的双相I型障碍患者和85例年龄在30至79岁之间的健康个体。患者将接受稳定的药物治疗，未发生情绪发作或显著的情绪或精神病症状，并且无其他轴I障碍，包括当前或近期的药物滥用或依赖。参与者将接受诊断和临床病史、当前症状、认知能力以及通过磁共振成像测量的大脑结构和功能的评估。将测量PFC灰质厚度、与PFC连接的神经束中的白色组织、静息灌注以及工作记忆任务期间前额叶皮层和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病理过程，并使未来的纵向调查使用最好的措施，并集中在最有可能的时间段的变化。