Du Yujing, Li Xixuan, Zhang Shufang, Tan Jingxuan, Zhu Ying, Zhai Xuejia, Lu Yongning
Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277, Jiefang Avenue, Wuhan, Hubei, 430022, China.
Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, China.
Metab Brain Dis. 2025 Sep 10;40(7):265. doi: 10.1007/s11011-025-01682-y.
Major depression disorder (MDD) is a mental condition that significantly threatens both physical and psychological health. This study aimed to discern variances in plasma metabolic profiles between MDD sufferers and healthy counterparts. Additionally, we tracked the hospitalization journey of MDD patients to investigate the normalization of metabolic irregularities through conventional treatment in the form of self-control. Ultra-Performance Liquid Chromatography - Mass Spectrometry was employed to analyze the metabolic profiles of 47 plasma samples, including 12 controls and 12 MDD patients at three distinct clinical stages (untreated baseline, 1-month post-treatment, and 2-month post-treatment). Multivariate statistical analysis and K-means clustering were executed to pinpoint significantly different metabolites between the groups and specific metabolites showing an ideal trend of variation. Subsequently, these metabolites were mapped onto Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways to preliminarily explore the potential mechanism of metabolic shifts in MDD. We identified 14 significantly different metabolites between MDD patients and controls. Among these, the relative levels of 9-hydroperoxy octadecadienoic acid, imidazoleacetic acid, thromboxane B2, and arachidonic acid displayed a regular trend of variation post-treatment. Further integration analysis yielded a novel metabolite-pathway network comprising these 4 specific metabolites and 8 pathways. These findings suggest that transitions in metabolic pathways during the onset and treatment of MDD are primarily governed by lipid metabolism and its associated signaling pathway system, with the involvement of histidine metabolism. The identified metabolites hold promise for diagnosing and evaluating the therapeutic efficacy of MDD, and provide a foundation for future research into the potential mechanisms underlying MDD.
重度抑郁症（MDD）是一种严重威胁身心健康的精神疾病。本研究旨在识别MDD患者与健康对照者血浆代谢谱的差异。此外，我们追踪了MDD患者的住院过程，以研究通过自我控制形式的常规治疗使代谢异常正常化的情况。采用超高效液相色谱-质谱联用技术分析47份血浆样本的代谢谱，其中包括12名对照者以及12名处于三个不同临床阶段（未治疗基线、治疗后1个月和治疗后2个月）的MDD患者。进行多变量统计分析和K均值聚类，以确定组间显著不同的代谢物以及呈现理想变化趋势的特定代谢物。随后，将这些代谢物映射到京都基因与基因组百科全书（KEGG）通路，以初步探索MDD中代谢变化的潜在机制。我们确定了MDD患者与对照者之间14种显著不同的代谢物。其中，9-氢过氧十八碳二烯酸、咪唑乙酸、血栓素B2和花生四烯酸的相对水平在治疗后呈现出规律的变化趋势。进一步的整合分析产生了一个由这4种特定代谢物和8条通路组成的新型代谢物-通路网络。这些发现表明，MDD发病和治疗期间代谢途径的转变主要受脂质代谢及其相关信号通路系统的调控，同时涉及组氨酸代谢。所鉴定的代谢物有望用于MDD的诊断和治疗效果评估，并为未来研究MDD潜在机制提供基础。
