Developing Brain Function in Adolescent Bipolar Disorder

发展青少年双相情感障碍的大脑功能

• 批准号: 8212236
• 负责人: Mani N Pavuluri
• 金额: $ 77.15万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8212236
• 关键词: 14 year old; 17 year old; Achievement; Adolescence; Adolescent; Affect; Affective; Age; Amygdaloid structure; Anterior; Antidepressive Agents; Antipsychotic Agents; Area; Attention; Behavior; Behavior assessment; Behavioral; Bipolar Disorder; Brain; Brain region; Child; Clinical; Cognitive; Cognitive deficits; Color; Corpus striatum structure; Data; Deterioration; Development; Diffuse; Disease Progression; Early identification; Early treatment; Emotional; Emotions; Equipment and supply inventories; Functional Magnetic Resonance Imaging; Functional disorder; Future; Growth; Hamilton Rating Scale for Depression; Home environment; Impaired cognition; Impairment; Impulsivity; Laboratories; Life; Longitudinal Studies; Manic; Measures; Memory; Mental Health; Modeling; Mood stabilizers; National Institute of Mental Health; Neurocognitive; Neurocognitive Deficit; Newly Diagnosed; Patients; Pattern; Performance; Pharmaceutical Preparations; Prefrontal Cortex; Preventive; Process; Psyche structure; Public Health; Regulation; Relative (related person); Sampling; Series; Short-Term Memory; Solid; Staging; Symptoms; Testing; Time; Work; Youth; aged; base; brain behavior; cingulate cortex; cognitive function; comparison group; computerized; demographics; design; executive function; experience; flexibility; functional disability; innovation; neural circuit; operation; patient population; peer; public health relevance; response; suicidal behavior; tool

DESCRIPTION (provided by applicant): This study aims to characterize the atypical developmental trajectory of functional brain circuitry and neurocognitive function in adolescent bipolar disorder (ABD). Our functional magnetic resonance imaging (fMRI) studies in ABD patients have found impairment in fronto-limbic and fronto-striatal circuitry. These abnormalities may underlie the affective and cognitive disturbances that are central to the illness, and have broad implication for clinical course and functional disability. To date, most studies of ABD are cross-sectional and the developmental trajectory of functional brain maturation remains poorly characterized. Therefore, we propose to extend our prior work in this area by examining the maturational trajectory of interfacing affective and cognitive brain circuitry, and to assess its impact on neurocognitive development and illness course. Our primary aim is to define the developmental changes in brain circuitry functioning in 12-14 year old recent-onset ABD patients over a three-year period during which marked changes in cognitive and affective processes are known to typically occur. The sample will include 80 newly diagnosed manic or mixed ABD patients who are stimulant and antidepressant naive, and have had no more than 4 weeks of lifetime treatment with mood stabilizers or antipsychotics. Unmedicated patients will be examined at baseline and followed subsequently on an annual basis for three years, i.e., in very early stages of disease progression, using innovative neurocognitive and fMRI paradigms to probe affective and cognitive neurocircuitry function and clinical course. A demographic and IQ matched healthy comparison group (n=80) will be studied longitudinally in parallel with the patient group. This study is innovative in its examination of the cognitive developmental and brain maturational trajectory of ABD, and will contribute to an understanding of the ways in which maturational changes in affective and cognitive neurocircuitry function deviate from normal development, and how these processes contribute to course of illness. Thus, the study will provide important information about ABD that is needed to develop more effective and neurobiologically-based early interventions, which could potentially minimize or reverse pathophysiological processes and reduce functional disability in ABD patients. PUBLIC HEALTH RELEVANCE: Adolescent Bipolar Disorder (ABD) is a serious illness associated with significant affect dysregulation and cognitive dysfunction, with high rates of suicidal behavior and academic under achievement. Therefore, the proposed study aims to understand the developmental function of the interfacing affective and cognitive neural circuitry and clinical course in ABD patients, relative to a healthy comparison group, from the time of their first presentation at 12-14 years of age till they turn 15-17 years of age i.e., over a 3 year window of steep brain maturation and cognitive development. A comprehensive understanding of the "brain-behavior development and deviance from the norm" in ABD will provide future opportunities for preventive efforts by facilitating early identification, moving a step closer to safer, more effective and neurobiologically informed early interventions for youths affected by ABD.

描述（由申请人提供）：本研究旨在表征青少年双相情感障碍（ABD）功能性脑电路和神经认知功能的非典型发育轨迹。我们在ABD患者中的功能磁共振成像（fMRI）研究发现，在额 - 边缘和额叶纹状体电路中发现了损害。这些异常可能是对疾病至关重要的情感和认知障碍的基础，并且对临床病程和功能障碍具有广泛的影响。迄今为止，ABD的大多数研究都是横断面的，功能性脑成熟的发育轨迹仍然很差。因此，我们建议通过检查接口和认知脑电路的成熟轨迹，并评估其对神经认知能力发展和疾病过程的影响，从而扩展我们在这一领域的先前工作。 我们的主要目的是定义在三年内，近期发作的ABD患者的脑电路功能的发育变化，在此期间，通常已知认知和情感过程的明显变化。该样本将包括80例新诊断的躁狂或混合ABD患者，这些患者是刺激性和抗抑郁药天真的，并且对情绪稳定剂或抗精神病药的终身治疗不超过4周。未经药物的患者将在基线时检查三年，即在疾病进展的早期阶段，使用创新的神经认知和fMRI范式来探测情感和认知神经循环功能和临床课程。人口统计学和智商匹配的健康比较组（n = 80）将与患者组平行研究。这项研究在检查ABD的认知发展和大脑成熟轨迹方面具有创新性，并将有助于理解情感和认知神经通路功能的成熟方式偏离正常发育的方式，以及这些过程如何有助于疾病。因此，该研究将提供有关ABD的重要信息，以开发出更有效和神经生物学的早期干预措施，这可能会最大程度地减少或逆转病理生理过程并减少ABD患者的功能障碍。 公共卫生相关性：青少年躁郁症（ABD）是一种严重的疾病，与重大影响失调和认知功能障碍有关，具有高自杀行为和学术成就的率很高。因此，拟议的研究旨在了解ABD患者的接口情感和认知神经回路和临床课程的发展功能，相对于健康比较组，从他们的第12-14岁时的首次介绍到15-17岁的年龄，即在陡峭的大脑成熟和认知能力发展的3年窗口中。对ABD中“大脑行为发展和与规范的偏差”的全面理解将通过促进早期识别来为预防努力提供机会，使对受ABD影响的年轻人更加安全，更有效，更有效，更有效，更有效和神经生物学知情的早期干预措施。