重性抑郁症中医辨证分型的神经化学、代谢组学和神经影像学的鉴别研究

There is heterogeneity in patients with depression. Many scholars propose that individualization of antidepressant achieves better outcomes. However, the scientific theoretical basis of individualized treatment is still quite weak. Different clinical subtypes of depression and their possible biomarkers are critically needed to provide the individualization with theoretical base. Diagnostic types of major depression disorder (MDD) based on the Theory of Traditional Chinese Medicine (TCM) and possible differentiations in neurobiochemistry, metabonomics and neuroimaging could be one of ways to explore the biomarkers and support the theory of the individualized treatment..The objectives of this study is to explore if there are any differences in neurobiochemistry, metabonomics and neuroimaging (1) at the baseline, between the subjects who are the normal controls (C Group) and who both meet diagnostic criteria of the Diagnostic and Statistical Manual of 5th edition (DSM-V) on MDD and TCM criteria of ‘pattern of Liver Depression and Qi Stagnation (LDQS)’ or ‘pattern of Deficiency of Both Heart and Spleen (DBHS)’ (T Group); (2) at the baseline, between the MDD subjects of LDQS and DBHS; (3) after 6-week venlafaxine administration, between the MDD subjects of LDQS and DBHS. 50 subjects in T Group and 25 in C Group are recruited in the study and the main laboratory tests include High Performance Liquid Chromatography(HPLC), Gas Chromatography-Mass Spectrum(GCMS) and neuroimaging DTI technology. The hypothesized results will be of help to clarify the biological basis of MDD with LDQS and with DBHS, to provide the TCM with further scientific evidence, to explore the pathogenesis of depression, to improve the objective diagnosis of depression, and to promote targeted interventions by Western medicine, TCM or both..

抑郁症患者存在着异质性，个体化抗抑郁药物能取得更有效的抗抑郁治疗效果。但个体化治疗科学理论基础还非常薄弱，我们需要探寻抑郁症的不同临床亚型及其生物学标记，这将可能成为个体化治疗的重要理论基础，应用神经生化、代谢组学及神经影像学探讨抑郁症证候,能更准确反映生物体系的状态,揭示抑郁症的本质。.本研究收集50例符合DSM-Ⅴ诊断标准同时中医辨证为肝郁气滞或心脾两虚证的重度抑郁症患者，采用高效液相荧光法、气质联用法、神经影像学DTI技术， 比较肝郁气滞或心脾两虚证的重度抑郁症患者与健康对照组比较在神经化学，代谢组学和神经影像学有无不同；比较两型重度抑郁症患者在神经化学，代谢组学和神经影像学的差异；文拉法辛治疗6周后的以上指标是否有变化。明确抑郁症肝郁气滞、心脾两虚的物质基础,论证中医辨证是否有现代科学依据，初步探索抑郁症的发病机制，为提高抑郁症诊断的客观化和药物干预的针对性奠定基础。

本研究收集44例符合DSM-Ⅴ诊断标准同时中医辨证为肝郁气滞或心脾两虚证的重度抑郁症患者，同时收集28例健康对照组，采用高效液相荧光法、气质联用法、神经影像学DTI技术，比较两型重度抑郁症患者在神经化学，代谢组学和神经影像学的差异；以及文拉法辛治疗6周后的治疗反应。探寻抑郁症的不同临床亚型及其生物学标记，这将可能成为个体化治疗的重要理论基础。结果发现：神经影像学方面，与其他两组比较，肝郁气滞型患者的多个连接变量在角回、中部及优势区枕叶脑回、距状沟、海希尔氏回表现为明显的不同。心脾两虚组在脑岛、海马旁回、优势半球颞叶端、后扣带回处连接增强。另外，额眶回、颞极处存在结构异常。 脑岛连接与抑郁严重程度存在明显的负相关，并能区分肝郁气滞型和心脾两虚型，具有敏感性和特异性。代谢组学方面，与健康组比较，肝郁气滞组在L-亮氨酸、棕榈酸、L-缬氨酸、柠檬酸、L-色氨酸、3-羟基丁酸存在明显不同。而心脾两虚组在L-亮氨酸、异乳糖、L-色氨酸、硬脂酸、L-异亮氨酸、L-蛋氨酸、L-缬氨酸存在明显不同。以上指标可以作为区别健康组与肝郁气滞或心脾两虚的生物学指标。研究发现，抑郁症负性情绪可能与视觉与听觉有关的颞枕叶网络异常有关。脑岛连接与抑郁严重程度存在明显的负相关，并能区分肝郁气滞型和心脾两虚型，具有敏感性和特异性。代谢组学方面，发现肝郁气滞主要表现为氨基酸神经递质类的单氨合成异常有关，包括氨酰基-tRNA生物合成通路、缬氨酸、亮氨酸、异亮氨酸的生物合成通路、丁烯酸酯代谢、苯基丙胺酸代谢、甘氨酸、苏氨酸、丝氨酸代谢通路，而心脾两虚与支链氨基酸蛋白合成有关，包括氨酰基-tRNA生物合成通路、缬氨酸、亮氨酸、异亮氨酸的生物合成与降解通路。异丁酸可以作为潜在的鉴别肝郁气滞与心脾两虚的代谢物。神经化学方面，两型5-HT均与健康组存在差异。两型抑郁症治疗前后比较，发现与心脾两虚证比较，肝郁气滞型重性抑郁障碍疗效更好，文拉法辛更适用于肝郁气滞型重性抑郁障碍。