Searching for Endophenotypes of Bipolar Disorder

寻找双相情感障碍的内表型

• 批准号: 8257832
• 负责人: JAIR C SOARES
• 金额: $ 69.11万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-12 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8257832
• 关键词: Address; Affective; Amygdaloid structure; Anisotropy; Anterior; Atrophic; Behavioral; Bipolar Disorder; Brain; Brain Pathology; Brain imaging; Brain region; Case-Control Studies; Controlled Study; Data; Diffusion Magnetic Resonance Imaging; Dizygotic Twins; Emotional; Enrollment; Epidemiologic Studies; Etiology; Female; Functional disorder; Gender; Genes; Genetic; Genetic Predisposition to Disease; Health; Heritability; Hippocampus (Brain); Impairment; Lateral; Magnetic Resonance Imaging; Measures; Medial; Memory; Mental disorders; Moods; N-acetylaspartate; Neurocognitive; Pathology; Patients; Performance; Population; Prefrontal Cortex; Risk; Role; Scanning; Siblings; Spectrum Analysis; Symptoms; Temporal Lobe; cognitive neuroscience; density; design; endophenotype; executive function; gray matter; indexing; male; neurocognitive test; neuroimaging; proband; tool; white matter

DESCRIPTION (provided by applicant): The causes of bipolar disorder (BD) are unknown, but neuroimaging studies have identified abnormalities in fronto-limbic brain (FLB) regions, which parallel findings of neurocognitive impairment. There is growing evidence to support abnormalities in sub- regions of the prefrontal cortex (PFC) and medial temporal lobe. In particular, the most consistent findings implicate the dorsolateral PFC, anterior cingulate, amygdala and hippocampus. These brain regions are interlinked and abnormalities could result in emotional instability, behavioral activation and other symptoms seen in BD patients. The primary aim of our study is to determine the extent to which FLB pathology in BD is attributable to genetic effects. The relationship between FLB abnormalities and BD will be addressed in a control study of same-gender sibling pairs discordant for BD type I. We will enroll 60 male and female sibling pairs discordant for BD and 60 matched controls, in a 3 group design (BD probands, unaffected siblings and healthy controls). Each subject will undergo brain magnetic resonance imaging (MRI), spectroscopy (MRS), diffusion tensor imaging (DTI) scans and neurocognitive testing. We will examine the relationship between BD and FLB abnormalities, neurocognitive function and genetic vulnerability. We will use state-of-the art tools from brain imaging and cognitive neuroscience to study the contribution of familial factors in determining FLB impairment in sibling pairs discordant for BD. The study will further elucidate the pathophysiology of BD and the role of genetic factors in the genesis of such abnormalities. If our hypotheses are confirmed, this will indicate that FLB abnormalities in BD are heritable and could be viable endophenotypes in the search for the specific genes involved. PUBLIC HEALTH RELEVANCE: Bipolar disorder is a very prevalent psychiatric illness and a major health problem worldwide. This study will examine the role of heritability on key brain abnormalities involved in causation of bipolar disorder (BD). If our hypotheses are confirmed, this will indicate that abnormalities in fronto-limbic brain regions in patients with BD are heritable and could be utilized as "endophenotypes" to guide future research on the specific genes involved.

描述（由申请人提供）：双相情感障碍（BD）的原因尚不清楚，但神经影像学研究已发现额叶边缘脑（FLB）区域的异常，这与神经认知障碍的发现相似。越来越多的证据支持前额皮质（PFC）和内侧颞叶的亚区域存在异常。特别是，最一致的发现涉及背外侧 PFC、前扣带回、杏仁核和海马。这些大脑区域是相互关联的，异常可能导致双相情感障碍患者情绪不稳定、行为活跃和其他症状。 我们研究的主要目的是确定 BD 中的 FLB 病理在多大程度上可归因于遗传效应。 FLB 异常与 BD 之间的关系将在对 BD I 型不一致的同性兄弟姐妹对的对照研究中得到解决。我们将在 3 组设计（BD 先证者、未受影响的兄弟姐妹和健康对照）中招募 60 对 BD 不一致的男性和女性兄弟姐妹以及 60 名匹配的对照。每个受试者都将接受脑部磁共振成像（MRI）、光谱学（MRS）、扩散张量成像（DTI）扫描和神经认知测试。我们将研究 BD 和 FLB 异常、神经认知功能和遗传脆弱性之间的关系。 我们将使用脑成像和认知神经科学领域最先进的工具来研究家庭因素在确定 BD 不一致的兄弟姐妹中 FLB 损伤中的作用。该研究将进一步阐明双相情感障碍的病理生理学以及遗传因素在此类异常发生中的作用。如果我们的假设得到证实，这将表明 BD 中的 FLB 异常是可遗传的，并且在寻找所涉及的特定基因时可能是可行的内表型。 公共卫生相关性：双相情感障碍是一种非常普遍的精神疾病，也是世界范围内的一个主要健康问题。这项研究将探讨遗传性对导致双相情感障碍 (BD) 的关键大脑异常的作用。如果我们的假设得到证实，这将表明双相情感障碍患者额叶边缘大脑区域的异常是可遗传的，并且可以用作“内表型”来指导未来对所涉及的特定基因的研究。