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且代价高昂的精神疾病。未来几十年，老年精神疾病患者的数量将迅速增加，但针对老年双相情感障碍患者的研究却很少。特别是，人们对衰老导致的大脑结构和功能的变化知之甚少，而这些变化可能是认知能力恶化的原因。 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......涉及晚年情绪和焦虑症。”这项由一名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以及尖端技术，旨在（1）研究躁郁症和抑郁症患者前额皮质（PFC）的结构、功能和连接性与年龄相关的差异。这些差异是否大于由于正常年龄相关变化而预期的差异，(2) 检查灰质和白质结构完整性是否充当年龄与 PFC 功能和功能连接之间关系的可能中介，以及 (3) 检查是否PFC 功能和功能连接作为年龄和认知表现之间关系的可能中介。重要的二次分析将检查有关双向情感障碍慢性病和病程测量的类似问题，例如自首次发作以来的持续时间、躁狂和抑郁发作的次数以及精神药物的累积暴露。 PFC 结构和功能缺陷是双相病理学的公认特征，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，其程度比正常衰老时预期的要严重，但尚未有研究将 PFC 灰质大小、白质完整性和组织、静息灌注、功能性大脑反应和对双相情感障碍和健康个体一生中大脑变化的单次研究中的连接性。我们的研究还旨在研究与年龄相关的大脑测量值之间的相互关系以及与认知表现之间的关系。我们将采用横断面设计来研究 85 名青少年或年轻成人发病的 I 型双相情感障碍患者和 85 名年龄在 30 至 79 岁之间的健康个体。患者将得到稳定的药物治疗，不会出现情绪发作或明显的情绪或精神病症状，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。参与者将接受诊断和临床病史、当前症状、认知表现以及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 连接的束中的白质组织、工作记忆任务期间前额皮质和连接区域的静息灌注和功能反应。这项研究的结果将有助于描述双相情感障碍的大脑病理过程，并能够使用最佳措施并关注最有可能发生变化的时间段进行未来的纵向研究。 公共卫生相关性： 对于患有双相情感障碍的成年人的大脑在衰老过程中如何变化以及这些变化是否与健康衰老时所见的不同，人们知之甚少。我们将研究年龄与磁共振成像测量的前额皮质灰质厚度、白质组织和完整性以及稳定双相情感障碍患者和健康个体认知活动期间功能反应的关系。我们还将研究大脑测量值之间的相互关系以及与认知能力之间的关系，并研究其他慢性测量值如何与双相情感障碍组的年龄差异相关。这项研究的结果将提高我们对衰老如何影响双相情感障碍大脑异常的认识，并可能提出旨在防止负面影响并利用任何积极变化的新疗法。