Comprehensive Analysis Strategy of Nervous–Endocrine–Immune-Related Metabolites to Evaluate Arachidonic Acid as a Novel Diagnostic Biomarker in Depression

Abstract

Depression is one of the most complex multifactorial diseases affected by genetic and environmental factors. The molecular mechanism underlying depression remains largely unclear. To address this issue, a novel nervous–endocrine–immune (NEI) network module was used to find the metabolites and evaluate the diagnostic ability of patients with depression. During this process, metabolites were acquired from a professional depression metabolism database. Over-representation analysis was performed using IMPaLA. Then, the metabolite–metabolite interaction (MMI) network of the NEI system was used to select key metabolites. Finally, the receiver operating characteristic curve analysis was evaluated for the diagnostic ability of arachidonic acid. The results show that the numbers of the nervous system, endocrine system, and immune system pathways are 10, 19, and 12 and the numbers of metabolites are 38, 52, and 13, respectively. The selected shared metabolite-enriched pathways can be 97.56% of the NEI-related pathways. Arachidonic acid was extracted from the NEI system network by using an optimization formula and validated by in vivo experiments. It was indicated that the proposed model was good at screening arachidonic acid for the diagnosis of depression. This method provides reliable evidences and references for the diagnosis and mechanism research of other related diseases.

Causal Effects of 1400 Blood Metabolites And Sleep Disorders: A Mendelian Randomization Study

“…Abnormal metabolism of arachidonic acid (AA) is closely associated with neuroendocrine immune (NEI) mechanisms and can be used as a reliable metabolic marker for the diagnosis of depression (31). The importance of plasma long-chain fatty acid levels (especially arachidonic acid) as an important assessment was emphasized in an investigation of the interaction between sleep quality, stress, depressive symptoms, and polyunsaturated fatty acid status in hypertensive patients (32).…”

Effect of Shenqi Jieyu formula on inflammatory response pathway in hippocampus of postpartum depression rats

“…COX-2, 5-LOX, sEH, and EETs belong to three metabolic pathways of arachidonic acid (AA) metabolism. 5-LOX and COX-2 are mainly involved in promoting inflammation reaction and are associated with depression [ 35 , 36 ]. Inhibition of 5-lipoxygenase (5-LOX) expression increases sucrose consumption, shortens the latency period of the water maze test, and reduces the number of errors in the step-down test in rats subjected to ongoing stress [ 5 ].…”

ProMENDA: an updated resource for proteomic and metabolomic characterization in depression

“…Therefore, MENDA was developed to present the manually curated metabolic characterization (with 5,600 metabolite entries) in the context of depression [15]. Since its first release in 2019, multiple integrated studies have employed MENDA to generate meaningful biological insights [16][17][18][19]. However, the number of metabolomics studies has doubled since the first release, and the core dataset warrants an update.…”