Metabolomic changes in animal models of depression: a systematic analysis

Abstract

Extensive research has been carried out on the metabolomic changes in animal models of depression; however, there is no general agreement about which metabolites exhibit constant changes. Therefore, the aim of this study was to identify consistently altered metabolites in large-scale metabolomics studies of depression models. We performed vote counting analyses to identify consistently upregulated or downregulated metabolites in the brain, blood, and urine of animal models of depression based on 3743 differential metabolites from 241 animal metabolomics studies. We found that serotonin, dopamine, gamma-aminobutyric acid, norepinephrine, N-acetyl-L-aspartic acid, anandamide, and tryptophan were downregulated in the brain, while kynurenine, myo-inositol, hydroxykynurenine, and the kynurenine to tryptophan ratio were upregulated. Regarding blood metabolites, tryptophan, leucine, tyrosine, valine, trimethylamine N-oxide, proline, oleamide, pyruvic acid, and serotonin were downregulated, while N-acetyl glycoprotein, corticosterone, and glutamine were upregulated. Moreover, citric acid, oxoglutaric acid, proline, tryptophan, creatine, betaine, L-dopa, palmitic acid, and pimelic acid were downregulated, and hippuric acid was upregulated in urine. We also identified consistently altered metabolites in the hippocampus, prefrontal cortex, serum, and plasma. These findings suggested that metabolomic changes in depression models are characterized by decreased neurotransmitter and increased kynurenine metabolite levels in the brain, decreased amino acid and increased corticosterone levels in blood, and imbalanced energy metabolism and microbial metabolites in urine. This study contributes to existing knowledge of metabolomic changes in depression and revealed that the reproducibility of candidate metabolites was inadequate in previous studies.

Integrated 16S rRNA sequencing and metabolomics analysis to investigate the antidepressant role of Yang-Xin-Jie-Yu decoction on microbe-gut-metabolite in chronic unpredictable mild stress-induced depression rat model

“…Moreover, we found that these altered amino acid neurotransmitters enriched in the amino acid metabolism pathway of taurine and hypotaurine metabolism, phenylalanine metabolism, and glutathione metabolism. These results are in line with the findings of a systematic analyse that indicated abnormalities of amino acid neurotransmitters in depression models (Pu et al, 2021).…”

Branched-chain amino acids linked to depression in young adults

“…Reviews of depression indicate at least five major biological systems are involved in depression, namely, inflammation, neuroendocrine, neurotransmitter, growth factor, and metabolic (Strawbridge et al, 2017;Zwolinska et al, 2021); biomarkers in these areas have been investigated using many approaches, including genetics (Flint and Kendler, 2014), epigenetics (Dalton et al, 2014), metabolomics (Bot et al, 2020), and the gut microbiome (Qin et al, 2022). Metabolomic investigations have been used in studies of somatic health conditions for many years and have more recently been used in psychiatry (Martins-de-Souza, 2014;Guest et al, 2016;Bot et al, 2020;Pu et al, 2021). Metabolomic approaches--in particular untargeted approaches, which use a broad panel of metabolite information to investigate associations--have been harnessed to generate new ideas and hypotheses in mental health (Bot et al, 2020;Whipp et al, 2021b), and continue to be useful in studies of depression.…”

Effects of pharmacological treatment on metabolomic alterations in animal models of depression

“…Moreover, vote counting is an effective method for selecting molecules to be independently validated by external studies, with the assumption that a reliable differential molecule is robust enough to show significance across multiple studies [ 30 ]. This approach has been recently implemented in other research integrating large-scale metabolomics studies [ 31 , 32 ].…”