Du Yue, Wei Jinxue, Zhang Zijian, Yang Xiao, Wang Min, Wang Yu, Qi Xiongwei, Zhao Liansheng, Tian Yang, Guo Wanjun, Wang Qiang, Deng Wei, Li Minli, Lin Dongtao, Li Tao, Ma Xiaohong
Psychiatric Laboratory and Mental Health Center, West China Hospital of Sichuan University, Chengdu, China.
West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, China.
Front Psychiatry. 2021 Sep 27;12:644555. doi: 10.3389/fpsyt.2021.644555. eCollection 2021.
Major depressive disorder (MDD) is a common disease which is complicated by metabolic disorder. Although MDD has been studied relatively intensively, its metabolism is yet to be elucidated. To profile the global pathophysiological processes of MDD patients, we used metabolomics to identify differential metabolites and applied a new database Metabolite set enrichment analysis (MSEA) to discover dysfunctions of metabolic pathways of this disease. Hydrophilic metabolomics were applied to identify metabolites by profiling the plasma from 55 MDD patients and 100 sex-, gender-, BMI-matched healthy controls. The metabolites were then analyzed in MSEA in an attempt to discover different metabolic pathways. To investigate dysregulated pathways, we further divided MDD patients into two cohorts: (1) MDD patients with anxiety symptoms and (2) MDD patients without anxiety symptoms. Metabolites which were hit in those pathways correlated with depressive and anxiety symptoms. Altogether, 17 metabolic pathways were enriched in MDD patients, and 23 metabolites were hit in those pathways. Three metabolic pathways were enriched in MDD patients without anxiety, including glycine and serine metabolism, arginine and proline metabolism, and phenylalanine and tyrosine metabolism. In addition, L-glutamic acid was positively correlated with the severity of depression and retardation if hit in MDD patients without anxiety symptoms. Different kinds of metabolic pathophysiological processes were found in MDD patients. Disorder of glycine and serine metabolism was observed in both MDD patients with anxiety and those without.
重度抑郁症（MDD）是一种常伴有代谢紊乱的疾病。尽管对MDD的研究相对深入，但其代谢情况仍有待阐明。为了剖析MDD患者的整体病理生理过程，我们使用代谢组学来识别差异代谢物，并应用一个新的数据库代谢物集富集分析（MSEA）来发现该疾病代谢途径的功能障碍。应用亲水代谢组学，通过分析55例MDD患者和100例性别、年龄、体重指数匹配的健康对照者的血浆来识别代谢物。然后在MSEA中对这些代谢物进行分析，试图发现不同的代谢途径。为了研究失调的途径，我们进一步将MDD患者分为两个队列：（1）有焦虑症状的MDD患者和（2）无焦虑症状的MDD患者。在这些途径中出现的代谢物与抑郁和焦虑症状相关。MDD患者共富集了17条代谢途径，这些途径中有23种代谢物被命中。无焦虑的MDD患者富集了三条代谢途径，包括甘氨酸和丝氨酸代谢、精氨酸和脯氨酸代谢以及苯丙氨酸和酪氨酸代谢。此外，在无焦虑症状的MDD患者中，如果L-谷氨酸被命中，则与抑郁和迟缓的严重程度呈正相关。在MDD患者中发现了不同类型的代谢病理生理过程。在有焦虑症状和无焦虑症状的MDD患者中均观察到甘氨酸和丝氨酸代谢紊乱。
