双相障碍工作记忆损害的海马相关记忆环路机制初探

Although the impairment of working memory is an important clinical characteristic of cognitive function impairments in patients with bipolar disorder (BPD), it is still poorly understood. Working memory impairment could hinder rehabilitation of social function and prognosis of disease. Previous studies have found that social function could not recover to pre-disease level in patients with BPD, suggesting working memory and the hippocampus related memory circuits impairments may involved in this pathological mechanism. In current study, neuropsychological test battery and MRI based multi-modality brain image technology will be used to further explore the association between working memory impairments and hippocampus related memory circuits in different BPD sub-type (BD-I/BD-II) and different stages of disease (depression episode/hypomania episode/ stable phase). In order to verify whether the working memory impairments could be the characteristic indicators for BPD, and whether the hippocampus related memory circuits involved in this pathological mechanism, mood stabilizers will be used in this study to examine the association between the remission of symptoms and the improvements in working memory. This study could provide evidence for the assumptions that working memory impairments is one of the stable phenotypes for BPD and the hippocampal related memory circuits involving in this pathological mechanism. These results could deepen our understandings of this important pathophysiological process of rehabilitation, and provide a new insight on promoting the social functions in patients with BPD.

工作记忆损害虽然是双相障碍认知功能改变的一种重要临床表现，影响患者社会功能康复和疾病预后，但却尚未得到临床的重视。既往研究发现，双相障碍患者症状缓解后其社会功能并未恢复至病前水平，究其原因可能与患者持续的工作记忆损害有关, 其病理基础可能涉及海马相关记忆环路受损。本课题拟应用成套神经心理测试工具和基于MRI的多模态脑影像学技术进一步观察双相障碍不同亚型（双相障碍I型/II型）、不同疾病阶段（抑郁发作期/轻躁狂发作期/稳定期）的工作记忆损害与海马相关记忆环路之间的联系。应用心境稳定剂治疗，观察临床症状缓解与工作记忆损害改善之间的联系，验证工作记忆损害是否为双相障碍的特征性指标、海马相关记忆环路是否参与其病理机制。本课题预期将会对工作记忆损害是否为双相障碍的内表型提供参考依据，为海马相关记忆环路参与其病理机制提出理论假设，深化我们对这一重要病理生理过程的理解，为促进患者社会功能康复提供新思路。

目的：应用威斯康辛卡片测试、Stroop任务测验，和基于MRI的多模态脑影像学技术观察双相障碍不同亚型、不同疾病阶段的工作记忆损害与海马相关记忆环路之间的联系。并应用心境稳定剂治疗，观察临床症状缓解与工作记忆损害改善之间的联系，验证工作记忆损害是否为双相障碍的特征性指标、海马相关记忆环路是否参与其病理机制。.方法：入组双相障碍患者（BD）95例，健康对照（HC）91例，并与129例抑郁症患者（MDD）进行对照，分别比较人口学和疾病临床特征、工作记忆测试、脑结构影像差异。并且在患者接受心境稳定剂治疗之后，比较稳定期与抑郁发作急性期的差别。.结果：1）BD组较之MDD组在抑郁首次发作的年龄更早以及抑郁发作次数更多，更多的人处于未婚状态，受教育年限也较MDD少。 2）双相II型较之I型在基线状态下YMRS总分更低，经心境稳定剂治疗之后，双相II型抑郁发作的预后要优于双相I型患者。 3）无论是WCST还是Stroop测试，均显示BD、MDD与HC之间在多个评定指标间有显著性差异，但BD与MDD组间差异无显著性。 4）MDD组和BD组在急性期治疗结束后，MDD组Stroop测试的反应时间快于BD组。 5) 而BD患者的右侧小脑前叶、左侧尾状核、左侧顶下小叶、右侧额中回、左侧额中回体积较健康对照减少，MDD患者较BD患者右侧尾状核、左侧额中回体积减少。此外，BD与MDD患者较之HC均表现出多个脑区白质FA值降低。.结论：BD患者的社会功能和处境比MDD患者更为糟糕，而双相I型患者的预后更差。左侧额中回脑区的灰质密度减少可以作为检测BD的生物学标志物，此外白质FA值降低也可作为参考指标。