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）：本研究旨在描述青少年双相情感障碍（ABD）中功能性脑回路和神经认知功能的非典型发育轨迹。我们对 ABD 患者进行的功能性磁共振成像 (fMRI) 研究发现，额叶边缘和额纹状体回路存在损伤。这些异常可能是疾病核心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，大多数 ABD 研究都是横断面的，并且功能性大脑成熟的发展轨迹仍然很少被描述。因此，我们建议通过检查情感和认知大脑回路的成熟轨迹来扩展我们在这一领域的先前工作，并评估其对神经认知发展和疾病过程的影响。 我们的主要目标是确定 12-14 岁新发 ABD 患者在三年时间内大脑回路功能的发展变化，在此期间通常会发生认知和情感过程的显着变化。该样本将包括 80 名新诊断的躁狂或混合性 ABD 患者，他们从未服用过兴奋剂和抗抑郁药，并且一生中接受过情绪稳定剂或抗精神病药治疗不超过 4 周。未接受药物治疗的患者将在基线时接受检查，并在三年内每年进行一次随访，即在疾病进展的早期阶段，使用创新的神经认知和功能磁共振成像范例来探测情感和认知神经回路功能和临床过程。将与患者组同时纵向研究人口统计和智商匹配的健康对照组（n = 80）。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回路功能的成熟变化偏离正常发展的方式，以及这些过程如何促进 ABD 的进程。疾病。因此，该研究将提供有关 ABD 的重要信息，这些信息是开发更有效且基于神经生物学的早期干预措施所需的，这可能会最大限度地减少或逆转 ABD 患者的病理生理过程并减少功能障碍。 公共健康相关性：青少年双相情感障碍 (ABD) 是一种与严重情感失调和认知功能障碍相关的严重疾病，自杀行为发生率很高，学业成绩不佳。因此，本研究旨在了解 ABD 患者相对于健康对照组，从 12-14 岁首次出现直至成年期间，情感和认知神经回路接口的发育功能和临床病程。 15-17 岁，即大脑急剧成熟和认知发展的时间超过 3 年。对 ABD 中“大脑行为发育和偏离规范”的全面了解，将为未来的预防工作提供机会，促进早期识别，为受 ABD 影响的青少年提供更安全、更有效和更符合神经生物学信息的早期干预措施。