Searching for Endophenotypes of Bipolar Disorder

描述(申请人提供)：双相情感障碍(BD)的原因尚不清楚，但神经成像研究已发现额叶边缘脑(FLB)区域异常，这与神经认知障碍的结果相似。越来越多的证据支持前额叶皮质(PFC)和内侧颞叶亚区的异常。特别是，最一致的发现涉及到PFC背外侧、前扣带回、杏仁核和海马体。这些大脑区域是相互关联的，异常可能导致BD患者的情绪不稳定、行为激活和其他症状。我们研究的主要目的是确定BD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BD I型的同性同胞配对的对照研究中解决。我们将招募60名BD男性和女性同胞配对和60名匹配的对照，采用3组设计(BD先证者、未受影响的同胞和健康对照)。每个受试者都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损性之间的关系。我们将使用脑成像和认知神经科学的最新工具来研究家族因素在确定BD不协调的同胞对FLB损害中的作用。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的FLB异常是可遗传的，可能是寻找特定基因的可行内表型。

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.