Study protocol: exercise training for treating major depressive disorder in multiple sclerosis
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ABSTRACT:
SUBMITTER: Motl R
PROVIDER: S-EPMC11022372 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Major depressive disorder (MDD) exhibits numerous clinical, epidemiological, and molecular features that are consistent with partially inherited and partially acquired epigenetic misregulation. We performed microarray based DNA modification study of MDD, utilizing affected and unaffected samples from white blood cells from monozygotic twins discordant for MDD, post-mortem prefrontal cortex tissues, and sperm samples. We performed DNA methylome analysis on white blood cells from monozygotic twins discordant for depression (n=200), pre-frontal cortex (n=71), and germline samples (n=33) from affected individuals and controls (total n=304). DNA samples were enriched for unmodified fraction of the genome using DNA-modification sensitive restriction enzyme digestion followed by adaptor-mediated PCR. The enriched fractions were labelled with a fluorescent dye (Cy5) and hybridized onto the array with a common reference pool (Cy3) generated from individuals unrelated to this study.
2012-04-27 | E-GEOD-37579 | biostudies-arrayexpress
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
Project description:BackgroundMajor depressive disorder (MDD) is associated with chronic biases in the allocation of attention and recollection of personal memories. Impaired flexibility in attention and autobiographical memory retrieval is seen to both maintain current symptoms and predict future depression. Development of innovative interventions to reduce maladaptive cognitive patterns and improve cognitive flexibility in the domain of memory may therefore advance current treatment approaches for depression. Memory specificity training and cognitive bias modification techniques have both shown some promise in improving cognitive flexibility. Here we outline plans for a trial of an innovative memory flexibility training programme, MemFlex, which advances current training techniques with the aim of improving flexibility of autobiographical memory retrieval. This trial seeks to estimate the efficacy of MemFlex, provide data on feasibility, and begin to explore mechanisms of change.Methods/designWe plan a single-blind, randomised, controlled, patient-level trial in which 50 individuals with MDD will complete either psychoeducation (n = 25) or MemFlex (n = 25). After completing pre-treatment measures and an orientation session, participants complete eight workbook-based sessions at home. Participants will then be assessed at post-treatment and at 3 month follow-up. The co-primary outcomes are depressive symptoms and diagnostic status at 3 month follow-up. The secondary outcomes are memory flexibility at post-treatment and number of depression free days at 3 month follow-up. Other process outcomes and mediators of any treatment effects will also be explored.DiscussionThis trial will establish the efficacy of MemFlex in improving memory flexibility, and reducing depressive symptoms. Any effects on process measures related to relapse may also indicate whether MemFlex may be helpful in reducing vulnerability to future depressive episodes. The low-intensity and workbook-based format of the programme may improve access to psychological therapies, and, if encouraging, the results of this study will provide a platform for later-phase trials.Trial registrationNCT02371291 (ClinicalTrials.gov), registered 9 February 2015.
| S-EPMC4632349 | 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.
2011-10-05 | GSE19738 | GEO
Project description:Unipolar depression is one of the most common diseases worldwide and is associated with a higher cardiovascular risk partly due to reduced aerobic capacity.Therefore, the aim of our study was to examine whether a structured aerobic training program can improve aerobic capacity in inpatients with MDD (major depressive disorder).Overall, 25 patients (13 women, 12 men) diagnosed with MDD were included in the study. Parameters of aerobic capacity, such as maximum performance, maximum oxygen consumption, and VAT (ventilatory anaerobic threshold), were assessed on a bicycle ergometer before and 6 weeks after a training period (three times per week for 45 min on two endurance machines). In addition, a constant load test was carried out at 50% of the maximum performance prior to and after the training period. The performance data were compared with 25 healthy controls matched for sex, age, and body mass index before and after the training period.Compared to controls, patients with MDD had significantly lower aerobic capacity. After training, there was a significant improvement in their performance data. A significant difference remained only for VAT between patients with MDD and healthy controls.With regard to the coincidence of MDD with cardiovascular and cardiometabolic disorders, a structured supervised exercise program carried out during hospitalization is a useful supplement for patients with MDD.
| S-EPMC4842901 | biostudies-other
Project description:BackgroundChanges in lifestyle, finances and work status during COVID-19 lockdowns may have led to biopsychosocial changes in people with pre-existing vulnerabilities such as Major Depressive Disorders (MDDs) and Multiple Sclerosis (MS).MethodsData were collected as a part of the RADAR-CNS (Remote Assessment of Disease and Relapse-Central Nervous System) program. We analyzed the following data from long-term participants in a decentralized multinational study: symptoms of depression, heart rate (HR) during the day and night; social activity; sedentary state, steps and physical activity of varying intensity. Linear mixed-effects regression analyses with repeated measures were fitted to assess the changes among three time periods (pre, during and post-lockdown) across the groups, adjusting for depression severity before the pandemic and gender.ResultsParticipants with MDDs (N = 255) and MS (N = 214) were included in the analyses. Overall, depressive symptoms remained stable across the three periods in both groups. A lower mean HR and HR variation were observed between pre and during lockdown during the day for MDDs and during the night for MS. HR variation during rest periods also decreased between pre- and post-lockdown in both clinical conditions. We observed a reduction in physical activity for MDDs and MS upon the introduction of lockdowns. The group with MDDs exhibited a net increase in social interaction via social network apps over the three periods.ConclusionsBehavioral responses to the lockdown measured by social activity, physical activity and HR may reflect changes in stress in people with MDDs and MS. Remote technology monitoring might promptly activate an early warning of physical and social alterations in these stressful situations. Future studies must explore how stress does or does not impact depression severity.
| S-EPMC9738639 | biostudies-literature
Project description:Major depressive disorder (MDD) exhibits numerous clinical and molecular features that are consistent with putative epigenetic misregulation. Despite growing interest in epigenetic studies of psychiatric diseases, the methodologies guiding such studies have not been well defined. We performed DNA modification analysis in white blood cells from monozygotic twins discordant for MDD, in brain prefrontal cortex, and germline (sperm) samples from affected individuals and control subjects (total N = 304) using 8.1K CpG island microarrays and fine mapping. In addition to the traditional locus-by-locus comparisons, we explored the potential of new analytical approaches in epigenomic studies. In the microarray experiment, we detected a number of nominally significant DNA modification differences in MDD and validated selected targets using bisulfite pyrosequencing. Some MDD epigenetic changes, however, overlapped across brain, blood, and sperm more often than expected by chance. We also demonstrated that stratification for disease severity and age may increase the statistical power of epimutation detection. Finally, a series of new analytical approaches, such as DNA modification networks and machine-learning algorithms using binary and quantitative depression phenotypes, provided additional insights on the epigenetic contributions to MDD. Mapping epigenetic differences in MDD (and other psychiatric diseases) is a complex task. However, combining traditional and innovative analytical strategies may lead to identification of disease-specific etiopathogenic epimutations.
2012-04-28 | GSE37579 | GEO
Project description:EarlyCause. Cross-sectional study of major depressive disorder
| PRJEB76994 | ENA
Project description:Background/objectiveRecent literature has identified links between vitamin B12 deficiency and depression.We compared the clinical response of SSRI-monotherapy with that of B12-augmentation in a sample of depressed patients with low normal B12 levels who responded inadequately to the first trial with the SSRIs.MethodsPatients with depression and low normal B12 levels were randomized to a control arm (antidepressant only) or treatment arm (antidepressants and injectable vitamin B12 supplementation).ResultsA total of 199 depressed patients were screened. Out of 73 patients with low normal B12 levels 34 (47%) were randomized to the treatment group while 39 (53%) were randomized to the control arm. At three months follow up 100% of the treatment group showed at least a 20% reduction in HAM-D score, while only 69% in the control arm showed at least a 20% reduction in HAM-D score (p<0.001). The findings remained significant after adjusting for baseline HAM-D score (p=0.001).ConclusionVitamin B12 supplementation with antidepressants significantly improved depressive symptoms in our cohort.
| S-EPMC3856388 | biostudies-literature
Project description:Identify blood proteins relevant to paroxetine response in patients with major depressive disorder (MDD)
2022-05-20 | PXD028947 | Pride