Gut Microbiota Changes in Patients With Major Depressive Disorder Treated With Vortioxetine.
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ABSTRACT:
SUBMITTER: Ye X
PROVIDER: S-EPMC8138160 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background: Anhedonia is a common, persistent, and disabling phenomenon in treated adults with Major Depressive Disorder (MDD). Hitherto, relatively few antidepressant agents have been evaluated with respect to their effect on anhedonia in MDD. Methods: This is a post-hoc analysis of a primary study that sought to evaluate the sensitivity to change of the THINC-integrated tool (THINC-it) in MDD (ClinicalTrials.gov Identifier: NCT03053362). Adults meeting DSM-5 criteria for MDD with at least moderate depressive symptom severity [i.e., Montgomery Åsberg Depression Rating Scale (MADRS) total score ≥20] were eligible. Subjects were recruited between October 2017 and August 2018 in Toronto, Ontario at the Brain and Cognition Discovery Foundation. All subjects received open-label vortioxetine (10-20 mg/day, flexibly-dosed) for 8 weeks. Herein, the primary outcome of interest was the change from baseline to endpoint in the Snaith-Hamilton Pleasure Scale (SHAPS) total score, as well as the MADRS anhedonia factor. The mediational effects of improvements in anhedonia on general function and quality of life, as measured by the Sheehan Disability Scale (SDS) and the 5-Item World Health Organization Well-Being Index (WHO-5), were secondarily assessed. Results: A total of 100 subjects with MDD were enrolled in the primary study and began treatment with vortioxetine. Vortioxetine significantly improved anhedonia as evidenced by significant baseline to endpoint improvements in SHAPS and MADRS anhedonia factor scores (p < 0.0001). Improvements in the SHAPS and the MADRS anhedonia factor correlated with improvements in general function (i.e., SDS) and quality of life (i.e., WHO-5) (p < 0.0001). Notably, improvements in anhedonia were found to mediate the association between improvements in overall depressive symptom severity (i.e., MADRS total score) and social functioning (i.e., social life component of the SDS) (p = 0.026). Conclusion: The unmet need in depression is to improve patient functioning and other patient-reported outcomes (e.g., quality of life). Antidepressant interventions capable of attenuating anhedonia as well as cognitive dysfunction in MDD may help in this regard, as improvement in these domains have been associated with improvement in psychosocial function and quality of life.
| S-EPMC6365446 | biostudies-literature
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.
| S-EPMC8323045 | biostudies-literature
Project description:BackgroundEfficacy has been proven for vortioxetine in short-term and long-term treatment of major depressive disorder (MDD), with broad beneficial effects on emotional, physical and cognitive symptoms. Limited specific data on the effects of vortioxetine on depression-related physical symptoms have been published.MethodsA meta-analysis was carried out of five short-term multinational, double-blind, placebo-controlled studies. These studies were conducted in a total of 2105 adult MDD outpatients (18-75 years) with a major depressive episode of ⩾3 months' duration. Only patients treated with a dose of 5 or 10 mg vortioxetine (therapeutic doses) or placebo were included in this analysis. Efficacy assessment of vortioxetine on the physical symptoms of depression included all items of the Hamilton Depression Scale (HAM-D) assessing physical symptoms, and all somatic items in the Hamilton Anxiety Scale (HAM-A). A subgroup analysis in MDD patients with coexisting anxiety symptoms (i.e. those with a HAM-A ⩾20 at baseline) was also performed.ResultsA significant improvement ( p<0.05) of vortioxetine versus placebo was observed on all HAM-D items measuring physical symptoms, except for the somatic gastrointestinal symptoms and loss of weight items. Significant effects were also observed on the HAM-A somatic items: general somatic symptoms, gastrointestinal symptoms, and autonomic symptoms. In patients with a high baseline level of anxiety, a significant effect of vortioxetine was also observed on the physical symptoms of depression.ConclusionsThese analyses indicate that patients with MDD, including those with a high level of anxiety symptoms, have significant improvements in MDD-associated physical symptoms when treated with vortioxetine.
| S-EPMC6380624 | biostudies-literature
Project description:Although alterations in the gut microbiota have been linked to the pathophysiology of major depressive disorder (MDD), including through effects on the immune response, our understanding is deficient about the straight connection patterns among microbiota and MDD in patients. Male and female MDD patients were recruited: 46 patients with a current active MDD (a-MDD) and 22 in remission or with only mild symptoms (r-MDD). Forty-five healthy controls (HC) were also recruited. Psychopathological states were assessed, and fecal and blood samples were collected. Results indicated that the inducible nitric oxide synthase expression was higher in MDD patients compared with HC and the oxidative stress levels were greater in the a-MDD group. Furthermore, the lipopolysaccharide (an indirect marker of bacterial translocation) was higher in a-MDD patients compared with the other groups. Fecal samples did not cluster according to the presence or the absence of MDD. There were bacterial genera whose relative abundance was altered in MDD: Bilophila (2-fold) and Alistipes (1.5-fold) were higher, while Anaerostipes (1.5-fold) and Dialister (15-fold) were lower in MDD patients compared with HC. Patients with a-MDD presented higher relative abundance of Alistipes and Anaerostipes (1.5-fold) and a complete depletion of Dialister compared with HC. Patients with r-MDD presented higher abundance of Bilophila (2.5-fold) compared with HC. Thus, the abundance of bacterial genera and some immune pathways, both with potential implications in the pathophysiology of depression, appear to be altered in MDD, with the most noticeable changes occurring in patients with the worse clinical condition, the a-MDD group.
| S-EPMC8692500 | biostudies-literature
Project description:BackgroundAnxiety symptoms are common in patients with major depressive disorder (MDD) and usually confer worse treatment outcomes. The long-term, open-label AtWoRC study in working patients with MDD treated with vortioxetine demonstrated a significant correlation between severity of anxiety symptoms and impaired work productivity. This analysis was undertaken to further explore clinical characteristics and treatment outcomes in patients with different levels of severity of anxiety symptoms at baseline.MethodsPost hoc analysis in 199 working patients with MDD treated with vortioxetine (10-20 mg/day), stratified by Generalized Anxiety Disorder 7-item (GAD-7) score at baseline [mild/moderate anxiety (GAD-7 ⩽14), n = 83; severe anxiety (GAD-7 ⩾15), n = 116]. Associations were examined between GAD-7 and other outcome assessment scores at baseline. Observed mean changes from baseline to week 52 were compared between groups.ResultsPatients with severe anxiety had significantly worse depressive and cognitive symptoms, functioning, and work productivity at baseline than those with mild/moderate anxiety, but similar cognitive performance. Statistically significant improvements from baseline were seen for all outcomes after 52 weeks of vortioxetine treatment, with no significant differences observed between the two groups after adjustment for baseline anxiety scores.ConclusionTreatment with vortioxetine was associated with long-term improvement in clinical symptoms and measures of work productivity in patients with MDD in a real-world setting, irrespective of severity of anxiety symptoms at the start of treatment.
| S-EPMC8120527 | biostudies-literature
Project description:BackgroundGrowing evidence has shown that alterations in the gut microbiota composition were associated with a variety of neuropsychiatric conditions. However, whether such associations reflect causality remains unknown. We aimed to reveal the causal relationships among gut microbiota, metabolites, and neuropsychiatric disorders including Alzheimer's disease (AD), major depressive disorder (MDD), and schizophrenia (SCZ).MethodsA two-sample bi-directional Mendelian randomization analysis was performed by using genetic variants from genome-wide association studies as instrumental variables for gut microbiota, metabolites, AD, MDD, and SCZ, respectively.ResultsWe found suggestive associations of host-genetic-driven increase in Blautia (OR, 0.88; 95%CI, 0.79-0.99; P = 0.028) and elevated γ-aminobutyric acid (GABA) (0.96; 0.92-1.00; P = 0.034), a downstream product of Blautia-dependent arginine metabolism, with a lower risk of AD. Genetically increased Enterobacteriaceae family and Enterobacteriales order were potentially associated with a higher risk of SCZ (1.09; 1.00-1.18; P = 0.048), while Gammaproteobacteria class (0.90; 0.83-0.98; P = 0.011) was related to a lower risk for SCZ. Gut production of serotonin was potentially associated with an increased risk of SCZ (1.07; 1.00-1.15; P = 0.047). Furthermore, genetically increased Bacilli class was related to a higher risk of MDD (1.07; 1.02-1.12; P = 0.010). In the other direction, neuropsychiatric disorders altered gut microbiota composition.ConclusionsThese data for the first time provide evidence of potential causal links between gut microbiome and AD, MDD, and SCZ. GABA and serotonin may play an important role in gut microbiota-host crosstalk in AD and SCZ, respectively. Further investigations in understanding the underlying mechanisms of associations between gut microbiota and AD, MDD, and SCZ are required.
| S-EPMC7532639 | biostudies-literature
Project description:BackgroundMajor Depressive Episodes (MDEs) may characterise many psychiatric disorders. Its pharmacotherapy is laid with unmet needs, rendering the testing of new drugs necessary.ObjectiveTo compare the effects of vortioxetine with those of other antidepressants (OADs) in a 1-year naturalistic setting.MethodsWe included 126 adult patients with anMDE in the course of major depressive (MDD), bipolar (BD), or schizophrenia spectrum disorders (SSOPDs), with or without substance use disorder (SUD), who received 5-20 mg/day oral vortioxetine, and compared them with 100 patients receiving OADs at baseline and after 1, 3, 8, and 12 months on their scores on the MADRS, the CGIS, the 24-item BPRS, the YMRS, the Hamilton Anxiety Rating Scale, a Visual Analogue Scale for craving, the Columbia-Suicide Severity Rating Scale, and the WHOQOL-BREF.ResultsPatients on vortioxetine improved similarly to those on OADs on all measures, independently from having or not a comorbid SUD. However, they improved with time better than their OADcounterparts if affected by BD or SSOPDs, but not MDD, on the CGI-S, BPRS depression, anxiety, and manic symptoms. SUD hampered the response of anxiety to treatment. Men improved on depression with time better than women.ConclusionMDEs responded to vortioxetine similarly to OADs by improving in depression, general psychopathology, anxiety, suicidal thinking, and quality-of-life, independently from SUD comorbidity. MDEs of patients with BD or SSOPDs on vortioxetine responded better than that of patients on OADs. Clinical Trial Registration No. 17354N.
| S-EPMC9185761 | biostudies-literature
Project description:BackgroundMajor depressive disorder (MDD) and generalized anxiety disorder (GAD) are frequently comorbid.AimsTo assess the effectiveness of vortioxetine in patients with MDD and comorbid GAD.MethodsOpen-label, 8-week study (NCT04220996) in 100 adult outpatients with severe MDD and severe comorbid GAD receiving vortioxetine as first treatment for the current depressive episode or switching to vortioxetine due to inadequate response to another drug for depression. Vortioxetine starting dosage was 10 mg/day, with forced up-titration to 20 mg/day after 1 week. Response was defined as ⩾50% decrease in Montgomery-Åsberg Depression Rating Scale (MADRS) and/or Hamilton Anxiety Rating Scale (HAM-A) total score from baseline; remission defined as MADRS and/or HAM-A total score ⩽10.ResultsClinically meaningful and statistically significant improvements from baseline in symptoms of depression and anxiety, and overall functioning and health-related quality of life, were observed after 8 weeks' vortioxetine treatment (all changes p < 0.0001 vs baseline). At week 8, rates of MADRS response and remission were 61% and 35%, respectively. Corresponding rates of HAM-A response and remission were 55% and 42%. Response on both the MADRS and HAM-A scales was achieved by 52% of patients; 31% achieved remission on both scales. Vortioxetine dose up-titration was well tolerated; no unexpected adverse events were reported.ConclusionVortioxetine demonstrates effectiveness in significantly reducing symptoms of both depression and anxiety in patients with severe MDD comorbid with severe GAD. Findings support increasing vortioxetine dosage to 20 mg/day early in the course of therapy, and show that this may be achieved without compromising tolerability.
| S-EPMC9112621 | biostudies-literature
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.
| S-EPMC7550660 | biostudies-literature
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.
2011-10-04 | E-GEOD-19738 | biostudies-arrayexpress