Search

Objective: Although many works have been done, the objectively measured diagnostic biomarkers are not available. Thus, we conducted this study to identify potential biomarkers for objectively diagnosing depression and explore the role of gut microbiota in the onset of depression. Methods: Major depressive disorder (MDD) patients (n=56) and demographic data-matched healthy controls (HCs) (n=56) were included in this study. The gut microbiota in fecal samples and inflammation-related factors in serum were measured. Both univariate and multivariate statistical analyses were performed to identify the differential gut microbiota and inflammation-related factors. Results: Finally, 46 differential operational taxonomic units (OTUs) (60.9% OTUs belonging to Firmicutes) and ten differential inflammation-related factors were identified. Correlation analysis showed that there were significant correlations between 14 differential OTUs (9 OTUs belonging to Firmicutes and 5 OTUs belonging to family Lachnospiraceae under Firmicutes) and seven differential inflammation-related factors. Meanwhile, 14 differential OTUs (9 OTUs belonging to Firmicutes and 5 OTUs belonging to family Lachnospiraceae under Firmicutes) and five differential inflammation-related factors (adiponectin, apolipoprotein A1, alpha 1-antitrypsin, neutrophilicgranulocyte count/white blood cell count and basophil count) were significantly correlated to depression severity. A panel consisting of these five differential inflammation-related factors could effectively diagnose MDD patients from HCs. Conclusions: Our results suggested that Firmicutes, especially family Lachnospiraceae, might play a role in the onset of depression via affecting the inflammation levels of host, and these five differential inflammation-related factors could be potential biomarkers for objectively diagnosing MDD. [ABSTRACT FROM AUTHOR]

Background: Although many works have been conducted to explore the biomarkers for diagnosing major depressive disorder (MDD), the widely accepted biomarkers are still not identified. Thus, the combined application of serum metabolomics and fecal microbial communities was used to identify gut microbiota-derived inflammation-related serum metabolites as potential biomarkers for MDD. Methods: MDD patients and healthy controls (HCs) were included in this study. Both serum samples and fecal samples were collected. The liquid chromatography mass spectrometry (LC-MS) was used to detect the metabolites in serum samples, and the 16S rRNA gene sequencing was used to analyze the gut microbiota compositions in fecal samples. Results: Totally, 60 MDD patients and 60 HCs were recruited. The 24 differential serum metabolites were identified, and 10 of these were inflammation-related metabolites. Three significantly affected inflammation-related pathways were identified using differential metabolites. The 17 differential genera were identified, and 14 of these genera belonged to phyla Firmicutes. Four significantly affected inflammation-related pathways were identified using differential genera. Five inflammation-related metabolites (LysoPC(16:0), deoxycholic acid, docosahexaenoic acid, taurocholic acid and LysoPC(20:0)) were identified as potential biomarkers. These potential biomarkers had significant correlations with genera belonged to phyla Firmicutes. The panel consisting of these biomarkers could effectively distinguish MDD patients from HCs with an area under the curve (AUC) of 0.95 in training set and 0.92 in testing set. Conclusion: These findings suggested that the disturbance of phyla Firmicutes might be involved in the onset of depression by regulating host's inflammatory response, and these potential biomarkers could be useful for future investigating the objective methods for diagnosing MDD. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) and suicide are two major health problems, but there are still no objective methods to diagnose MDD or suicidal ideation (SI). This study was conducted to identify potential biomarkers for diagnosing MDD patients with SI. Methods: First-episode drug-naïve MDD patients with SI and demographics-matched healthy controls (HCs) were recruited. First-episode drug-naïve MDD patients without SI were also included. The serum lipids, C-reactive protein (CRP), transferring (TRSF), homocysteine (HCY) and alpha 1-antitrypsin (AAT) in serum were detected. The univariate and multivariate statistical analyses were used to identify and validate the potential biomarkers. Results: The 86 HCs, 53 MDD patients with SI and 20 MDD patients without SI were included in this study. Four potential biomarkers were identified: AAT, TRSF, high-density lipoprotein cholesterol (HDLC), and apolipoprotein A1 (APOA1). After one month treatment, the levels of AAT and APOA1 were significantly improved. The panel consisting of these potential biomarkers had an excellent diagnostic performance, yielding an area under the ROC curve (AUC) of 0.994 and 0.990 in the training and testing set, respectively. Moreover, this panel could effectively distinguish MDD patients with SI from MDD patients without SI (AUC=0.928). Conclusion: These results showed that these potential biomarkers could facilitate the development of an objective method for diagnosing MDD patients with SI, and the decreased AAT levels in MDD patients might lead to the appearance of SI by resulting in the elevated inflammation. [ABSTRACT FROM AUTHOR]

Introduction: Major depressive disorder (MDD) is a highly prevalent mental disorder affecting millions of people worldwide. However, a clear causative etiology of MDD remains unknown. In this study, we aimed to identify critical protein alterations in plasma from patients with MDD and integrate our proteomics and previous metabolomics data to reveal significantly perturbed pathways in MDD. An isobaric tag for relative and absolute quantification (iTRAQ)-based quantitative proteomics approach was conducted to compare plasma protein expression between patients with depression and healthy controls (CON). Methods: For integrative analysis, Ingenuity Pathway Analysis software was used to analyze proteomics and metabolomics data and identify potential relationships among the differential proteins and metabolites. Results: A total of 74 proteins were significantly changed in patients with depression compared with those in healthy CON. Bioinformatics analysis of differential proteins revealed significant alterations in lipid transport and metabolic function, including apolipoproteins (APOE, APOC4 and APOA5), and the serine protease inhibitor. According to canonical pathway analysis, the top five statistically significant pathways were related to lipid transport, inflammation and immunity. Conclusion: Causal network analysis by integrating differential proteins and metabolites suggested that the disturbance of phospholipid metabolism might promote the inflammation in the central nervous system. [ABSTRACT FROM AUTHOR]

Objective: Our previous studies found that disturbances in gut microbiota might have a causative role in the onset of major depressive disorder (MDD). The aim of this study was to investigate whether there were sex differences in gut microbiota in patients with MDD. Patients and methods: First-episode drug-naïve MDD patients and healthy controls were included. 16S rRNA gene sequences extracted from the fecal samples of the included subjects were analyzed. Principal-coordinate analysis and partial least squares-discriminant analysis were used to assess whether there were sex-specific gut microbiota. A random forest algorithm was used to identify the differential operational taxonomic units. Linear discriminant-analysis effect size was further used to identify the dominant sex-specific phylotypes responsible for the differences between MDD patients and healthy controls. Results: In total, 57 and 74 differential operational taxonomic units responsible for separating female and male MDD patients from their healthy counterparts were identified. Compared with their healthy counterparts, increased Actinobacteria and decreased Bacteroidetes levels were found in female and male MDD patients, respectively. The most differentially abundant bacterial taxa in female and male MDD patients belonged to phyla Actinobacteria and Bacteroidia, respectively. Meanwhile, female and male MDD patients had different dominant phylotypes. Conclusion: These results demonstrated that there were sex differences in gut microbiota in patients with MDD. The suitability of Actinobacteria and Bacteroidia as the sex-specific biomarkers for diagnosing MDD should be further explored. [ABSTRACT FROM AUTHOR]

Major depressive disorder is a serious mental disorder with high morbidity and mortality. The role of social stress in the development of depression remains unclear. Here, we used the social defeat stress paradigm to induce depression-like behavior in rats, then evaluated the behavior of the rats and measured metabolic changes in the prefrontal cortex using gas chromatography-mass spectrometry. Within the first week after the social defeat procedure, the sucrose preference test (SPT), open field test (OFT), elevated plus maze (EPM) and forced swim test (FST) were conducted to examine the depressive-like and anxiety-like behaviors. For our metabolite analysis, multivariate statistics were applied to observe the distribution of all samples and to differentiate the socially defeated group from the control group. Ingenuity pathway analysis was used to find the potential relationships among the differential metabolites. In the OFT and EPM, there were no significant differences between the two experimental groups. In the SPT and FST, socially defeated rats showed less sucrose intake and longer immobility time compared with control rats. Metabolic profiling identified 25 significant variables with good predictability. Ingenuity pathways analysis revealed that “Hereditary Disorder, Neurological Disease, Lipid Metabolism” was the most significantly altered network. Stress-induced alterations of low molecular weight metabolites were observed in the prefrontal cortex of rats. Particularly, lipid metabolism, amino acid metabolism, and energy metabolism were significantly perturbed. The results of this study suggest that repeated social defeat can lead to metabolic changes and depression-like behavior in rats. [ABSTRACT FROM AUTHOR]

Backgrounds The effects of electroconvulsive therapy (ECT) and bilateral, left prefrontal, and right prefrontal repetitive transcranial magnetic stimulation (rTMS) on major depressive disorder (MDD) have not been adequately addressed by previous studies. Here, a multiple-treatments meta-analysis, which incorporates evidence from direct and indirect comparisons from a network of trials, was performed to assess the efficacy and acceptability of these four treatment modalities on MDD. Method The literature was searched for randomized controlled trials (RCTs) on ECT, bilateral rTMS, and unilateral rTMS for treating MDD up to May 2016. The main outcome measures were response and drop-out rates. Results Data were obtained from 25 studies consisting of 1288 individuals with MDD. ECT was non-significantly more efficacious than B-rTMS, R-rTMS, and L-rTMS. Left prefrontal rTMS was non −significantly less efficacious than all other treatment modalities. In terms of acceptability, R-rTMS was non-significantly better tolerated than ECT, B-rTMS, and L-rTMS. ECT was the most efficacious treatment with the cumulative probabilities of being the most efficacious treatment being: ECT (65%), B-rTMS (25%), R-rTMS (8%), and L-rTMS (2%). R-rTMS was the best-tolerated treatment with the cumulative probabilities of being the best-tolerated treatment being: R-rTMS (52%), B-rTMS (17%), L-rTMS (16%), and ECT (14%). Coherence analysis detected no statistically significant incoherence in any comparisons of direct with indirect evidence for the response rate and drop-out rate. Conclusions ECT was the most efficacious, but least tolerated, treatment, while R-rTMS was the best tolerated treatment for MDD. B-rTMS appears to have the most favorable balance between efficacy and acceptability. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a highly prevalent, debilitating mental illness of importance for global health. However, its molecular pathophysiology remains poorly understood. Combined proteomics and metabolomics approaches should provide a comprehensive understanding of MDD's etiology. The present study reports novel '-omics' insights from a rodent model of MDD. Cerebellar samples from chronic mild stressed (CMS)-treated depressed rats and controls were compared with a focus on the differentially expressed proteins and metabolites using isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics and gas chromotography/mass spectrometry (GC-MS) metabolomics techniques, respectively. The combined analyses found significant alterations associated with cerebellar energy metabolism, as indicated by (1) abnormal amino acid metabolism accompanied by corresponding metabolic enzymatic alterations and disturbed protein turnover, (2) increased glycolytic and tricarboxylic acid (TCA) cycle enzyme levels paralleled by changes in the concentrations of associated metabolites, and (3) perturbation of ATP biosynthesis through adenosine accompanied by perturbation of the mitochondrial respiratory chain. To the best of our knowledge, this study is the first to integrate proteomics and metabolomics analyses to examine the pathophysiological mechanism(s) underlying MDD in a CMS rodent model of depression. These results can offer important insights into the pathogenesis of MDD. [ABSTRACT FROM AUTHOR]

Abstract: Previous studies have demonstrated inconsistent findings regarding the efficacy of bilateral vs. unilateral repetitive transcranial magnetic stimulation (rTMS) in treating major depressive disorder (MDD). Therefore, this meta-analysis was conducted to compare the efficacy of these two rTMS modalities. Data were obtained from seven randomized controlled trials (RCTs) consisting of 509 subjects. Bilateral and unilateral rTMS displayed comparable efficacy in treating MDD with a pooled odds ratios of 1.06 (95% confidence interval (CI)=0.58–1.91) for response rates and 1.05 (95% CI=0.52–2.11) for remission rates. Subgroup analysis found that bilateral rTMS was equally effective in comparison with both left and right unilateral rTMS. No significant differences in drop-out rates were found. No publication bias was detected. In conclusion, the pooled examination demonstrated that bilateral rTMS displays comparable anti-depressant efficacy and acceptability to unilateral rTMS in treating MDD. These findings suggest that simultaneous rTMS of the right and left dorsolateral prefrontal cortices in MDD patients does not provide marginal benefits in terms of efficacy or acceptability. As the number of RCTs included here was limited, further large-scale multi-center RCTs are required to validate our conclusions. [Copyright &y& Elsevier]

Abstract: Plasma amino acids levels were measured in first-onset treatment-naïve depressed patients (n=26) and healthy controls (n=25) using a mass spectrometry-based method. One of the major findings was that a logistic regression model constructed from tryptophan, glutamine and cysteine discriminated depressed subjects from controls with a receiver-operating-characteristic curve integral of 0.90. [Copyright &y& Elsevier]