An integrated meta-analysis of peripheral blood metabolites and biological functions in major depressive disorder

Major depressive disorder (MDD) is a serious mental illness, characterized by high morbidity, which has increased in recent decades. However, the molecular mechanisms underlying MDD remain unclear. Previous studies have identified altered metabolic profiles in peripheral tissues associated with MDD. Using curated metabolic characterization data from a large sample of MDD patients, we meta-analyzed the results of metabolites in peripheral blood. Pathway and network analyses were then performed to elucidate the biological themes within these altered metabolites. We identified 23 differentially expressed metabolites between MDD patients and controls from 46 studies. MDD patients were characterized by higher levels of asymmetric dimethylarginine, tyramine, 2-hydroxybutyric acid, phosphatidylcholine (32:1), and taurochenodesoxycholic acid and lower levels of l-acetylcarnitine, creatinine, l-asparagine, l-glutamine, linoleic acid, pyruvic acid, palmitoleic acid, l-serine, oleic acid, myo-inositol, dodecanoic acid, l-methionine, hypoxanthine, palmitic acid, l-tryptophan, kynurenic acid, taurine, and 25-hydroxyvitamin D compared with controls. l-tryptophan and kynurenic acid were consistently downregulated in MDD patients, regardless of antidepressant exposure. Depression rating scores were negatively associated with decreased levels of l-tryptophan. Pathway and network analyses revealed altered amino acid metabolism and lipid metabolism, especially for the tryptophan–kynurenine pathway and fatty acid metabolism, in the peripheral system of MDD patients. Taken together, our integrated results revealed that metabolic changes in the peripheral blood were associated with MDD, particularly decreased l-tryptophan and kynurenic acid levels, and alterations in the tryptophan–kynurenine and fatty acid metabolism pathways. Our findings may facilitate biomarker development and the elucidation of the molecular mechanisms that underly MDD.