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.
Background In China, the shortage of doctors leads to stressful clinical work and increasing turnover. Medical students undergoing postgraduate specialty training will be the country’s medical workforce in the coming decades, but are also subject to high workloads and academic pressure. This may have significant implications for burnout and career choice regret. Despite the importance of burnout and career choice regret, the status and relationship of these aspects in Chinese neurology postgraduates are largely unexplored, and associated factors remain unknown. Methods This study investigated the prevalence of and factors influencing burnout and career choice regret among neurology postgraduates in China. We conducted a national cross-sectional study of Chinese neurology postgraduates. Data were collected using a self-administered questionnaire that covered demographic information, the Maslach Burnout Inventory, and additional item to assess career choice regret. Results Of 4902 neurology postgraduates, 2008 returned completed questionnaires (response rate 41%). After excluding incomplete questionnaires, data for 1814 participants were analyzed. In total, 83.6% of participants had experienced symptoms of burnout, and 46.6% reported career choice regret. Binary logistic regression analysis showed postgraduate entrance examination scores, marital status, and having children were associated with burnout (all P < 0.05). Career choice regret was the strongest risk factor for burnout (odds ratio [OR] = 3.17, 95% confidence interval [CI] 2.33–4.32). Multiple logistic regression showed postgraduates with shorter work or study hours per week (OR = 0.64, 95% CI 0.47–0.88) had a low risk for career choice regret, whereas married participants (OR = 1.54, 95% CI 1.07–2.20) had a high risk for career choice regret. No symptoms of burnout (OR = 0.33, 95% CI 0.24–0.45) was also associated with a low risk for career choice regret. Conclusions Burnout symptoms and career choice regret are prevalent among neurology postgraduates in China. Career choice regret is an important predictor of burnout. Further research on reducing burnout and career choice regret among neurology postgraduates is needed. Electronic supplementary material The online version of this article (10.1186/s12909-019-1601-3) contains supplementary material, which is available to authorized users.
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.
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