奖赏环路在双相障碍发病中的作用研究

Pathology of bipolar disorder (BD) has not been clear. There are robust evidence to suggest that dysfunction of dopamine (DA) circulation has effects on BD onset, which also contributes to regulate activity of brain reward circus. BD patients with different emotional status have structural and functional abnormality in reward circus, especially in limbic system and frontal lobe; however, the findings were not consistent and sensitive. The main reasons includes: heterogeneity of sample, different experimental design (cross sectional or longitudinal) and different functional magnetic resonance imaging (fMRI) data analysis. The present study is longitudinal. In attempting to understand role of reward circus in BD, we will examine BD patients with different emotional status (depressive, manic, euthymic) and health control by event-related and resting fMRI combined with DA concentration in peripheral blood and gene testing. There are three main purposes in this study: to observe different activity pattern of reward circus and DA concentration among four groups; to investigate change of brain activity and DA concentration when emotion transaction occurs; to compare data between recovery BD patients and euthymic BD patients. Thus, the present is important to understand BD pathology and clarify different pattern of brain activity and biomarker specifically related to BD.

双相障碍（Bipolar Disorder, BD）发病机制不明。现有证据提示BD存在多巴胺（Dopamine, DA）功能的周期性失调，DA传递的差异对奖赏脑区起调控作用。不同临床相的BD存在奖赏环路（主要是边缘叶通路和额叶皮层）功能、结构异常，但研究结果并不一致，可能与样本是否同质、横断面还是纵向跟踪、功能磁共振（function MRI, fMRI）方法不同有关。为阐明奖赏环路在BD发病中的作用，我们拟采用任务与静息态fMRI、外周血DA浓度/基因相结合的方法，以抑郁相、躁狂相和缓解状态BD为对象，并与健康人群比较，观察（1）各组间奖赏环路及DA的差异；（2）对患者进行纵向观察，对在跟踪过程中临床相变化的患者再检测，比较同一个患者不同临床相的奖赏环路以及DA的差异；（3）分析转相与不转相的缓解期患者结果的差异性。研究对阐明BD的发病机制，为临床治愈的评估提供生物学指标有重要。

前额叶-边缘系统环路功能的异常是双相障碍(BD)的共同表现，而功能磁共振研究结果显示相同情绪状态下的BD患者在奖赏任务时腹侧纹状体的活跃程度结果不尽一致甚至相反，可能与使用不同任务相关。金钱奖赏延迟(MID)任务比情绪任务、卡片猜测任务与奖赏环路关系更密切，而且MID任务只涉及奖赏激活，不涉及其他认知领域。腹侧纹状体和前侧前额叶的功能连接只在缓解态时被研究过，而抑郁和躁狂态则未有相关研究。为阐明奖赏环路在BD发病中的作用，我们采用MID任务态功能磁共振及外周血多巴胺浓度的方法，对BD患者（抑郁相、躁狂相、缓解期）及正常人进行研究，比较各组间MID任务态下腹侧纹状体活跃水平、腹侧纹状体和前侧前额叶的功能连接及外周血多巴胺浓度的差异。本研究结果发现：BD抑郁相、缓解期在奖赏期待时的双侧腹侧纹状体活跃度较正常组下降，而BD躁狂相在奖赏期待时的双侧腹侧纹状体的活跃度较正常组升高，提示上述结果可能为BD的状态标志，可作为疗效指标。BD患者缓解期、抑郁相和躁狂相在奖赏期待时左侧腹侧纹状体和左侧前侧前额叶功能连接均较正常对照减低，推测与BD的发病机制相关。而双相三种状态下血浆多巴胺的水平较正常对照无明显差异。