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

描述(由申请人提供)：这是第二次提交的提案，延长我们的研究，单相抑郁和抗抑郁药物对皮质边缘连接和活性的影响，以调查双相情感障碍(BD)的病理生理学和锂治疗的效果。本研究将利用功能磁共振成像(FMRI)对80例未服药的BD患者(躁狂期40例，抑郁期40例)和40例匹配的健康受试者的皮质边缘激活和连接性进行研究。事先确定的感兴趣区域有：皮质情绪调节区-腹侧扣带前皮质(VACC)和边缘情绪产生区-特别是杏仁核(AMYG)，以及腹侧纹状体(VST)和内侧丘脑(MTHAL)。第一个目标是使用一种特定于连接性的测量-低频大胆波动(LFBF)相关性来测量静息稳定状态下的皮质边缘连接性。第二个目标是使用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激活。据推测，与健康受试者相比，两组BD患者的皮质边缘连接性都会降低。对于激活任务，假设是，与健康受试者相比，在被动观看负性和中性图片时，BD患者的激活度会降低，但BDD患者的激活度会高于BDM受试者。在主动的面部情绪识别任务中，BDM患者的杏仁核激活程度比BDD和健康受试者更大。第二个目的是调查锂治疗对同意参加研究治疗阶段ARM的患者皮质边缘激活和连接异常的影响。据推测，锂治疗将使基线时的皮质边缘激活和连接异常恢复正常。另一个次要目的是研究遗传因素，如5-HTT启动子连接区(5-HTTLPR)高表达和低表达基因型对fMRI检测激活和连接的影响。因此，据我们所知，这项研究将首次同时研究未用药患者BD两个阶段的脑激活和连接异常，并探讨治疗和基因分型的影响。这项研究还将建立一个研究大脑连接的实验范式，可以用来研究其他疾病。

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.