Searching for Endophenotypes of Bipolar Disorder

寻找双相情感障碍的内表型

• 批准号: 8544492
• 负责人: JAIR C SOARES
• 金额: $ 55.75万
• 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/8544492
• 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; public health relevance; 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.

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经确定了额叶边缘脑（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叶皮层（PFC）和内侧颞叶亚区域的异常。特别是，最一致的结果涉及背外侧PFC，前扣带回，杏仁核和海马。这些大脑区域是相互关联的，异常可能导致情绪不稳定，行为激活和BD患者中看到的其他症状。 我们研究的主要目的是确定BD中FLB病理学归因于遗传效应的程度。FLB异常和BD之间的关系将在BD I型不一致的同性同胞对的对照研究中得到解决。我们将在3组设计中（BD先证者、未受影响的兄弟姐妹和健康对照）招募60对BD不一致的男性和女性兄弟姐妹和60对匹配的对照。每例受试者将接受脑磁共振成像（MRI）、波谱（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易感性之间的关系。 我们将使用来自脑成像和认知神经科学的最先进的工具来研究家族因素在确定BD不一致的兄弟姐妹对的FLB损伤中的作用。这项研究将进一步阐明BD的病理生理学和遗传因素在这种异常发生中的作用。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。