Dysfunctional Cortico-Limbic Activity and Connectivity in Bipolar Disorder and Li

描述（由申请人提供）：这是第二次重新提交的提案，以扩展我们在单极抑郁症和抗抑郁药对皮质边缘连接和活动的影响的研究，以研究双相情感障碍（BD）的病理生理学和锂治疗的效果。本研究将使用功能磁共振成像（fMRI）研究80例未服药的双相障碍患者（40例躁狂期（BDM）和40例抑郁期（BDD））和40例匹配的健康受试者的皮质边缘激活和连通性。先验定义的感兴趣的区域是：皮质情绪调节区域-腹侧前扣带皮层（vACC）和边缘情绪产生区域-特别是杏仁核（AMYG）以及腹侧纹状体（VST）和内侧丘脑（MTHAL）。第一个目的是使用连接特异性测量-低频BOLD波动（LFBF）相关性来测量静息稳定状态下皮质边缘的连通性。第二个目的是通过被动的图片观看任务和主动的面部情绪识别任务来测量皮质边缘的激活。假设与健康受试者相比，两组双相障碍患者的皮质边缘连通性都会降低。对于激活任务，假设是在被动观看消极图片和中性图片时，BD患者的激活程度比健康受试者低，但BDD患者的激活程度比BDM受试者高。在主动面部情绪识别任务中，BDM患者的杏仁核激活程度高于BDD和健康受试者。第二个目的是研究锂治疗对同意参加该研究治疗期的患者皮质边缘激活和连接异常的影响。假设锂治疗将使皮质边缘激活和连接异常在基线时正常化。另一个次要目的是研究遗传因素，如5-羟色胺转运体（5-HTT）启动子连接区（5-HTTLPR）多态性的高表达和低表达基因型对fMRI激活和连接测量的影响。因此，据我们所知，本研究将首次在未服药的双相障碍患者中同时研究两个阶段的脑激活和连通性异常，并探讨治疗和基因型的影响。这项研究也将建立一个研究大脑连接的实验范式，可以用于研究其他疾病。

DESCRIPTION (provided by applicant): This is a second resubmission of the proposal to extend our studies in unipolar depression and effects of antidepressants on corticolimbic connectivity and activity, to investigate the pathophysiology of Bipolar Disorder (BD) and effect of lithium treatment. This study will investigate, using functional magnetic resonance imaging (fMRI), corticolimbic activation and connectivity in 80 unmedicated BD patients - 40 in manic phase (BDM) and 40 in depressed phase (BDD), and 40 matched healthy subjects. The a priori defined regions of interest are: the cortical mood regulating region - ventral anterior cingulate cortex (vACC) and the limbic mood generating regions - particularly the amygdala (AMYG) and also ventral striatum (VST) and medial thalamus (MTHAL). The first aim is to measure corticolimbic connectivity in the resting steady- state using a connectivity specific measure - low frequency BOLD fluctuations (LFBF) correlations. The second aim is to measure corticolimbic activation using a passive picture viewing task as well as an active facial emotion recognition task. It is hypothesized that both BD groups will have decreased corticolimbic connectivity compared to healthy subjects. For activation tasks, the hypothesis is that in response to passive viewing of negative vs. neutral pictures BD patients will have decreased activation compared to healthy subjects but BDD patients will have a greater activation than BDM subjects. In the active facial emotion recognition task, BDM patients will have a greater amygdala activation than BDD and healthy subjects. A secondary aim is to investigate the effects of lithium treatment on corticolimbic activation and connectivity abnormalities in patients who agree to take part in the treatment phase arm of the study. It is hypothesized that lithium treatment will normalize corticolimbic activation and connectivity abnormalities seen at baseline. Another secondary aim is to investigate the effect of genetic factors such as the high expressing and low expressing genotypes of serotonin transporter (5-HTT) promoter linked region (5-HTTLPR) polymorphism on fMRI measures of activation and connectivity. Therefore, this study will, to the best of our knowledge, for the first time concurrently study brain activation and connectivity abnormalities in both phases of BD in unmedicated patients and also explore the effect of treatment and genotype. This study will also establish an experimental paradigm to study brain connectivity which could be used to investigate other disorders.