Project description:Postpartum depressive disorder (PPD) is a unique subtype of major depressive disorder and a substantial contributor to maternal morbidity and mortality. However, the pathogenesis of PPD has still remained elusive, and it may associate with genetic and environmental factors. Gut microbiota has already been proved to be associated with depression; however, a limited number of studies have concentrated on PPD. The present study aimed to explore the potential correlations between gut microbiota and PPD. In this study, 57 participants were enrolled, in which fecal samples of 28 patients with PPD and 16 healthy controls (HCs) were collected and then analyzed by high-throughput sequencing of the 16S ribosomal RNA (rRNA) gene. The results showed that diversity and composition of gut microbial communities were partly different between PPD patients and HCs. The relative abundance of Firmicutes phyla was lower in PPD patients. The levels of several predominant genera were significantly different between PPD patients and HCs. More importantly, the PPD patients experienced reduced levels of Faecalibacterium, Phascolarctobacterium, Butyricicoccus, and Lachnospiraceae, as well as increased levels of Enterobacteriaceae family. In addition, a correlation was observed between levels of Phascolarctobacterium, Lachnospiraceae, Faecalibacterium, and Tyzzerella.3 and the severity of depressive symptoms. Various kinds of bacteria, such as Lachnospiraceae and Faecalibacterium, were found to be associated with levels of sex hormones. This study indicated the correlation between gut microbiota and PPD, and gut microbiota-based biomarkers may be helpful for the diagnosis and treatment of PPD patients. However, further studies need to be conducted to clarify the cause-effect relationship between PPD patients and gut microbiota and to highlight the suitability of gut microbiome as a biomarker.
Project description:Microbiota-gut-brain axis signaling plays a pivotal role in mood disorders. The communication between the host and the gut microbiota may involve complex regulatory networks. Previous evidence showed that host-fecal microRNAs (miRNAs) interactions partly shaped gut microbiota composition. We hypothesized that some miRNAs are correlated with specific bacteria in the fecal samples in patients with major depressive disorder (MDD), and these miRNAs would show enrichment in pathways associated with MDD. MDD patients and healthy controls were recruited to collect fecal samples. We performed 16S ribosome RNA sequence using the Illumina MiSeq sequencers and analysis of 798 fecal miRNAs using the nCounter Human-v2 miRNA Panel in 20 subjects. We calculated the Spearman correlation coefficient for bacteria abundance and miRNA expressions, and analyzed the predicted miRNA pathways by enrichment analysis with false-discovery correction (FDR). A total of 270 genera and 798 miRNAs were detected in the fecal samples. Seven genera (Anaerostipes, Bacteroides, Bifidobacterium, Clostridium, Collinsella, Dialister, and Roseburia) had fold changes greater than one and were present in over 90% of all fecal samples. In particular, Bacteroides and Dialister significantly differed between the MDD and control groups (p-value < 0.05). The correlation coefficients between the seven genera and miRNAs in patients with MDD showed 48 pairs of positive correlations and 36 negative correlations (p-value < 0.01). For miRNA predicted functions, there were 57 predicted pathways with a p-value < 0.001, including MDD-associated pathways, axon guidance, circadian rhythm, dopaminergic synapse, focal adhesion, long-term potentiation, and neurotrophin signaling pathway. In the current pilot study, our findings suggest specific genera highly correlated with the predicted miRNA functions, which might provide clues for the interaction between host factors and gut microbiota via the microbiota-gut-brain axis. Follow-up studies with larger sample sizes and refined experimental design are essential to dissect the roles between gut microbiota and miRNAs for depression.
Project description:Dysbiosis is associated with various systemic disorders including irritable bowel syndrome (IBS). Fecal microbiota transplantation (FMT) might restore intestinal microbial balance. The study aimed to determine the safety and efficacy of FMT in IBS patients, as well as also positive predictors for FMT.This was a single-arm, open-label study. Eligible patients were diagnosed based on Rome III Diagnostic Criteria. Fecal materials were administered to the patient via colonoscopy. The primary end point was a change in the Bristol stool form scale at 4 weeks after FMT. Recovery to types 3-4 was considered a clinical response. The secondary end point was a change in intestinal microbiota and psychological status using the Hamilton Rating Scale.Ten patients were enrolled. Six patients achieved a clinical response. The diversity of patients 4 weeks after FMT increased significantly compared with patients before FMT, and that of responding patients was significantly higher than non-responder patients. The abundance of Bifidobacterium in effective donors was significantly higher than in ineffective donors and patients. Psychological status of all patients was significantly improved after FMT.FMT for patients with IBS is safe, and relatively effective. Bifidobacterium-rich fecal donor may be a positive predictor for successful FMT. Key Summary: (1) Dysbiosis is associated with various gastrointestinal disorders including IBS. (2) FMT has potential to restore intestinal microbial balance. (3) We showed that FMT improved stool form and psychological status of IBS patients. (4) Bifidobacterium-rich donor efficiently induced symbiosis in IBS patients.
Project description:Major depressive disorder (MDD) is a common disorder with a high prevalence and significant social and economic impacts. Nevertheless, the treatment of MDD is far from satisfactory. Acupuncture treatment has emerged as a promising method for treating MDD. However, the neural mechanism by which acupuncture reduces depressive symptoms is not fully understood. Studies have shown that the corticostriatal reward circuitry is associated with the pathophysiology of MDD; thus, we investigated the corticostriatal resting-state functional connectivity (rsFC) before and after real and sham acupuncture treatments combined with the antidepressant fluoxetine. Forty-six female major depressive patients were assigned to either verum acupuncture plus fluoxetine (n = 22) or sham acupuncture plus fluoxetine (n = 24) treatment for 8 weeks, and resting state functional magnetic resonance imaging (fMRI) data were collected before the first and after the last treatment sessions. The results showed that compared with sham acupuncture, the verum acupuncture group showed: (1) significantly increased rsFC between inferior ventral striatum and medial prefrontal cortex, ventral rostral putamen and amygdala/parahippocampus, as well as dorsal caudate and middle temporal gyrus; (2) significantly decreased rsFC between right ventral rostral putamen and right dorsolateral prefrontal cortex, and right dorsal caudate and bilateral cerebellar tonsil. The increased rsFC between the inferior ventral striatum and medial prefrontal cortex, ventral rostral putamen and amygdala/parahippocampus were significantly positively associated with decreased clinical scores (Montgomery-Åsberg Depression Rating Scale and Self-Rating Depression Scale scores) at the end of the eight-week treatment. Our findings suggest that acupuncture may achieve treatment effects by modulating the corticostriatal reward/motivation circuitry in MDD patients.
Project description:Vortioxetine hydrobromide is a common clinical medication for major depressive disorder (MDD). However, it remains unclear whether vortioxetine hydrobromide acts by affecting the structure and composition of gut microbiota. Here, we analyzed fecal samples from 28 healthy controls (HCs) and 26 patients with MDD before treatment with vortioxetine hydrobromide, at 4 weeks after treatment, and at 8 weeks after treatment. High-throughput pyrosequencing showed that, according to the Chao1 and Shannon indices, fecal bacterial α-diversity was higher in the patients with MDD than in the HCs (p < 0.05), but no significant differences were observed after vortioxetine hydrobromide treatment (p > 0.05). PCoA results revealed that the gut microbiota composition was significantly different between the MDD groups and HCs. Proteobacteria and Actinobacteria were strongly increased, whereas Firmicutes were significantly reduced in the MDD group compared with the HCs. After treatment with vortioxetine hydrobromide, Firmicutes were significantly increased, and the proportion of Bacteroidetes decreased. Most notably, Lachnospira, Roseburia, and Faecalibacterium were negatively correlated with the severity of depressive symptoms. Taken together, our data indicate changes in the fecal microbiota composition in MDD patients compared with HCs, and vortioxetine hydrobromide may treat MDD through regulation of the gut microflora.
Project description:Search for the biomarkers of major depressive disorder (MDD) has facilitated from the genes expressed in the patientâs blood cells. Because the severity of depressive symptoms and characteristics in patients with MDD are differed by the age at onset of first depressive episode, the potential transcriptomic markers in blood cells may also be different by the age at onset of MDD. In this study, we searched the transcriptomic markers of late-onset (onset ages ⥠50 years) MDD (LOD) from the expressed genes in blood cells, and identified state-dependent biomarkers in the patients. We assessed the expressed genes in blood cells by the microarray and found that the expression levels of 3,066 probes were state-dependently changed in the blood cells of patients with LOD. Elderly (age â¥50 years) outpatients and inpatients with MDD corresponding to a DSM-IV diagnosis of the melancholy type of MDD episodes were studied. The depressive state was measured using the Structured Interview Guide for the Hamilton Depression (SIGH-D) rating scale. Syndromal remission was defined as a stage in which a participant did not meet the diagnosis of a MINI major depressive episode for a period of 2 consecutive months and had a SIGH-D score of less than 8. Twelve healthy individuals were also recruited. Blood was obtained from the participants and analyzed using an Agilent SurePrint G3 Human GE 8Ã60K v2 Microarray (Design ID: 039494).
Project description:BackgroundOver 50% of patients with major depressive disorder (MDD) either do not tolerate or do not respond to antidepressant medications. Several preliminary studies have shown the benefits of acupuncture in the treatment of depression. We sought to determine whether a 2-point electroacupuncture protocol (verum acupuncture) would be beneficial for MDD, in comparison to needling at nonchannel scalp points with sham electrostimulation (control acupuncture).MethodFifty-three subjects aged 18-80 years, recruited via advertisement or referral, were included in the primary analysis of our randomized controlled trial, which was conducted from March 2004 through May 2007 at UPMC Shadyside, Center for Complementary Medicine, in Pittsburgh, Pennsylvania. Inclusion criteria were mild or moderate MDD (according to the Structured Clinical Interview for DSM-IV Axis I Disorders) and a score of 14 or higher on the Hamilton Depression Rating Scale (HDRS). Exclusion criteria included severe MDD, seizure disorder or risk for seizure disorder, psychosis, bipolar disorder, chronic MDD, treatment-resistent MDD, and history of substance abuse in the prior 6 months. Patients were randomized to receive twelve 30-minute sessions of verum versus control acupuncture over 6 to 8 weeks. The HDRS was the primary outcome measure. The UKU Side Effect Rating Scale was used to assess for adverse effects.ResultsTwenty-eight subjects were randomized to verum electroacupuncture and 25 to control acupuncture. The 2 groups did not differ with regard to gender, age, or baseline severity of depression. Both groups improved, with mean (SD) absolute HDRS score decreases of -6.6 (5.9) in the verum group and -7.6 (6.6) in the control group, corresponding to 37.5% and 41.3% relative decreases from baseline. There were no serious adverse events associated with either intervention, and endorsement of adverse effects was similar in the 2 groups.ConclusionsWe were unable to demonstrate a specific effect of electroacupuncture. Electroacupuncture and control acupuncture were equally well tolerated, and both resulted in similar absolute and relative improvement in depressive symptoms as measured by the HDRS.Trial registrationclinicaltrials.gov Identifier: NCT00071110.
Project description:ObjectiveThe etiology of major depressive disorder (MDD) is multi-factorial and has been associated with a perturbed gut microbiota. Thus, it is therefore of great importance to determine any variations in gut microbiota in patients with MDD.MethodsA systematic literature search was conducted including original research articles based on gut microbiota studies performed in patients with MDD. Demographic and clinical characteristics, applied methodology and observed gut microbiota composition were compared between included studies.ResultsSeventeen studies were included with a total of 738 patients with MDD and 782 healthy controls using different DNA purification methods, sequencing platforms and data analysis models. Four studies found a reduced α-diversity in patients with MDD, while gut microbiota compositions clustered separately according to β-diversity between patients and controls in twelve studies. Additionally, there was an increase in relative abundance of Eggerthella, Atopobium, and Bifidobacterium and a decreased relative abundance of Faecalibacterium in patients with MDD compared with healthy controls.ConclusionGut microbiota differs significantly when comparing patients with MDD and healthy controls, though inconsistently across studies. The heterogeneity in gut microbiota compositions between the studies may be explained by variations in study design.
Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.