应用多模态fMRI探讨交泰丸治疗抑郁症患者的脑机制研究

Jiaotai pill of ancient prescription is composed of two herbs of Huanglian and Rougui, is commonly used in the clinical treatment of insomnia and depression, insomnia is the most common symptoms of depression, also is a predisposing factor of depression. Depression is closely related to the neurotransmitter disorders, neurotransmitter disorders also play an important role in sleep disorders. Research group preliminary animal studies have shown that Jiaotai pill has antidepressant effect on the two kinds of animal behavior despair model of mouse tail suspension and forced swimming test, and has antidepressant effect by regulation NE and 5-HT content in hippocampus and cortex, but antidepressant mechanism of Jiaotai pill has not been reported in clinical literature. In this study, we select light and moderate depression patients as the research object, take HAMD scale for curative effect evaluation standard, combined application of functional magnetic resonance imaging technology(including BOLD-fMRI, DTI, MRS), and combined with plasma neurotransmitter and Wisconsin card sorting test, analysis effect of Jiaotai pill formula granules on neurotransmitters, alba microstructure and brain activity on resting state in patients with depression, observe whether Jiaotai pill is by regulating neurotransmitter to improve brain structure and function, and thus play therapeutic effect in patients with depression, from imaging level to explore brain mechanisms of Jiaotai pill on patients with depression.

古方交泰丸由黄连和肉桂两味药组成，是临床治疗失眠及抑郁症的常用方，失眠不但是抑郁症最常见症状，又是抑郁症加重的诱发因素。抑郁症的发生与神经递质功能紊乱密切相关，神经递质紊乱在睡眠障碍中也发挥着重要作用。课题组前期动物实验研究表明交泰丸在小鼠悬尾和强迫游泳实验两种动物行为绝望模型上具有抗抑郁作用，并可通过调节海马组织和皮质中NE和5-HT含量而发挥抗抑郁作用，但交泰丸抗抑郁的临床作用机制尚未见文献报道。本研究以轻中度抑郁症患者为研究对象，以HAMD量表为疗效评价标准，联合应用多模态fMRI技术（包括BOLD-fMRI、DTI、MRS），并结合血浆神经递质及威斯康星卡片分类心理测试，分析交泰丸配方颗粒剂对抑郁症患者神经递质、脑白质微观结构以及静息状态下脑功能活动的影响，观察交泰丸是否通过调节神经递质来改善脑结构及功能，从而对抑郁症患者发挥治疗作用，从影像学水平探讨交泰丸治疗抑郁症患者的脑机制。

本研究以轻中度抑郁症患者为研究对象，以汉密尔顿抑郁量表为疗效评价标准，联合应用多模态fMRI技术，并结合血浆神经递质及威斯康星卡片分类心理测试，分析交泰丸配方颗粒剂对抑郁症患者神经递质、脑结构以及脑功能活动的影响。结果显示：①交泰丸合用盐酸氟西汀治疗4周、治疗8周、停药4周后，均可明显减少轻中度抑郁症患者汉密尔顿抑郁量表评分，疗效以8周最佳；交泰丸合用盐酸氟西汀治疗8周后，汉密尔顿抑郁量表减分值明显优于单用盐酸氟西汀，总有效率优于单用盐酸氟西汀。②交泰丸合用盐酸氟西汀治疗轻中度抑郁症患者4周后、8周后，与治疗前中医证候评价量表评分比较，有显著性差异，疗效以8周最佳。交泰丸合用盐酸氟西汀治疗轻中度抑郁症患者8周后，中医证候评价量表减分值明显优于单用盐酸氟西汀。③交泰丸合用盐酸氟西汀治疗8周后，可以明显减少轻中度抑郁症患者威斯康星卡片分类测试中的错误应答数，增加完成分类数。④经过8周治疗后，盐酸氟西汀组、交泰丸合用盐酸氟西汀组血浆5羟色胺、去甲肾上腺素、多巴胺水平均明显升高；交泰丸合用盐酸氟西汀组血浆5羟色胺升高程度，明显优于单用盐酸氟西汀组。⑤交泰丸合用盐酸氟西汀治疗8周后，可以明显改善轻中度抑郁症患者右侧中央前回脑区、右侧缘上回脑区的功能像数据，疗效优于单用盐酸氟西汀。结果提示交泰丸联合盐酸氟西汀治疗抑郁症，可以增强盐酸氟西汀的抗抑郁疗效，在一定程度上改善抑郁症患者额叶功能，改善抑郁症患者的认知功能。交泰丸具有明显的抗抑郁作用，其机制与上调单胺类神经递质5羟色胺、去甲肾上腺素、多巴胺水平、改善右侧中央前回脑区、右侧缘上回脑区的功能有关。