NIMETOX-informed Precision Nomothetic Models of Major Depressive Disorder: Group, Phenome, and Individual Signatures

作者：Michael Maes, Mengqi Niu, Ping Wang, Annabel Maes, Yiping Luo, Chenkai Yangyang, Xiaoman Zhuang, Abbas F. Almulla, J B Li, Yingqian Zhang · 发表于：medRxiv · 年份：2026 · DOI：10.64898/2026.01.23.26344678 · 被引用次数：1 · 研究领域：Tryptophan and brain disorders、Gut microbiota and health、Metabolomics and Mass Spectrometry Studies

Abstract Background Major depressive disorder (MDD) is a neuro-immune-metabolic-oxidative (NIMETOX) disorder. Nevertheless, the effects of alterations in immune responsiveness, oxidative stress, antioxidant defenses, gut-derived short-chain fatty acids (SCFAs), metabolic hormones and adipokines on metabolomic modules and the MDD phenome have remained elusive. Methods Serum samples from 125 MDD inpatients and 40 healthy controls were analyzed using high-resolution metabolomics assays (liquid chromatography, mass spectrometry) in conjunction with assays of 68 additional NIMETOX markers. A machine learning pipeline was implemented to delineate the associations between MDD, clinical phenome features, metabolomic modules, and 68 NIMETOX biomarkers. Results The metabolomics and NIMETOX biomarkers distinguished MDD from controls with a cross-validated accuracy of >95%. Core biomarkers of MDD encompass (in order of decreasing importance) diacylglycerol lipotoxicity, phospholipid remodeling, fatty acid signaling, mitochondrial-redox dysfunction, diminished antioxidant defenses (including decreased paraoxonase 1 activity, Apolipoprotein A1, reverse cholesterol transport, ether lipids), inflammatory response, increased epidermal growth factor, disbalances in gut-derived SCFAs, increased oxidized high-density lipoprotein cholesterol, and changes in metabolic hormones. A large part of the variance in overall severity of illness (76.3%), physiosomatic symptoms (61.9%), current suicidal ...