Toward an Extended Definition of Major Depressive Disorder Symptomatology: Digital Assessment and Cross-validation Study.
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ABSTRACT: Background
Diagnosing major depressive disorder (MDD) is challenging, with diagnostic manuals failing to capture the wide range of clinical symptoms that are endorsed by individuals with this condition.Objective
This study aims to provide evidence for an extended definition of MDD symptomatology.Methods
Symptom data were collected via a digital assessment developed for a delta study. Random forest classification with nested cross-validation was used to distinguish between individuals with MDD and those with subthreshold symptomatology of the disorder using disorder-specific symptoms and transdiagnostic symptoms. The diagnostic performance of the Patient Health Questionnaire-9 was also examined.Results
A depression-specific model demonstrated good predictive performance when distinguishing between individuals with MDD (n=64) and those with subthreshold depression (n=140) (area under the receiver operating characteristic curve=0.89; sensitivity=82.4%; specificity=81.3%; accuracy=81.6%). The inclusion of transdiagnostic symptoms of psychopathology, including symptoms of depression, generalized anxiety disorder, insomnia, emotional instability, and panic disorder, significantly improved the model performance (area under the receiver operating characteristic curve=0.95; sensitivity=86.5%; specificity=90.8%; accuracy=89.5%). The Patient Health Questionnaire-9 was excellent at identifying MDD but overdiagnosed the condition (sensitivity=92.2%; specificity=54.3%; accuracy=66.2%).Conclusions
Our findings are in line with the notion that current diagnostic practices may present an overly narrow conception of mental health. Furthermore, our study provides proof-of-concept support for the clinical utility of a digital assessment to inform clinical decision-making in the evaluation of MDD.
SUBMITTER: Martin-Key NA
PROVIDER: S-EPMC8587324 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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: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
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2011-10-05 | GSE19738 | GEO
Project description:Currently, fewer than 40% of patients treated for major depressive disorder achieve remission with initial treatment. Identification of a biological marker that might improve these odds could have significant health and economic impact.To identify a candidate neuroimaging "treatment-specific biomarker" that predicts differential outcome to either medication or psychotherapy.Brain glucose metabolism was measured with positron emission tomography prior to treatment randomization to either escitalopram oxalate or cognitive behavior therapy for 12 weeks. Patients who did not remit on completion of their phase 1 treatment were offered enrollment in phase 2 comprising an additional 12 weeks of treatment with combination escitalopram and cognitive behavior therapy.Mood and anxiety disorders research program at an academic medical center.Men and women aged 18 to 60 years with currently untreated major depressive disorder.Randomized assignment to 12 weeks of treatment with either escitalopram oxalate (10-20 mg/d) or 16 sessions of manual-based cognitive behavior therapy.Remission, defined as a 17-item Hamilton depression rating scale score of 7 or less at both weeks 10 and 12, as assessed by raters blinded to treatment.Positive and negative predictors of remission were identified with a 2-way analysis of variance treatment (escitalopram or cognitive behavior therapy)?×?outcome (remission or nonresponse) interaction. Of 65 protocol completers, 38 patients with clear outcomes and usable positron emission tomography scans were included in the primary analysis: 12 remitters to cognitive behavior therapy, 11 remitters to escitalopram, 9 nonresponders to cognitive behavior therapy, and 6 nonresponders to escitalopram. Six limbic and cortical regions were identified, with the right anterior insula showing the most robust discriminant properties across groups (effect size?=?1.43). Insula hypometabolism (relative to whole-brain mean) was associated with remission to cognitive behavior therapy and poor response to escitalopram, while insula hypermetabolism was associated with remission to escitalopram and poor response to cognitive behavior therapy.If verified with prospective testing, the insula metabolism-based treatment-specific biomarker defined in this study provides the first objective marker, to our knowledge, to guide initial treatment selection for depression.Registered at clinicaltrials.gov (NCT00367341).
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2022-05-20 | PXD028947 | Pride
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2010-10-17 | E-GEOD-24095 | biostudies-arrayexpress
Project description:Major 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.We 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.This 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.NCT02371291 (ClinicalTrials.gov), registered 9 February 2015.
| S-EPMC4632349 | biostudies-literature
Project description:ObjectivesInteroception refers to the sensation, interpretation, and integration of internal somatic signals. Abnormalities in self-reported interoception are prevalent features of major depressive disorder (MDD) and may affect treatment outcomes. In the present study, we investigated the psychometric properties of the revised eight-dimensional and 37-item Multidimensional Assessment of Interoceptive Awareness questionnaire (the MAIA-2) in a severely depressed sample, after translating two updated scales (Not-Distracting, Not-Worrying) into German. Specifically, we examined the measure's internal consistency reliability, sensitivity to change, and minimal important differences (MID) with a focus on patient's antidepressive responses to treatment.MethodsThe study enrolled 110 participants (age: M = 46.85, SD = 11.23; female: 55.45%) undergoing hospital treatment, of whom 87 were included in the pre-post analysis. Participants completed a German translation of MAIA-2 and the Beck Depression Inventory-II (pre-/post-treatment). Internal consistency reliability was determined by Cronbach's α/McDonalds's ω, sensitivity to change was determined by effect sizes, and MIDs were determined by distribution- (0.5*SD) and anchor-based approaches (mean change method; ROC curve cut-points).ResultsDepression severity reduced over the course of treatment (Median = -65.22%), and 34.48% of patients achieved remission. Reliability was appropriate for post-treatment (range of ω: .70-.90), but questionable for two pre-treatment scales (Noticing: ω = .64; Not-Distracting: ω = .66). The eight dimensions of MAIA-2 were sensitive to change (standardized response mean: .32-.81; Cohen's effect size: .30-.92). Distribution-based MIDs (.38-.61) and anchor-based mean change MIDs (remission vs. partial response: .00-.85; partial response vs. nonresponse: .08-.88) were established on the group level. For six scales, ROC cut-points (remission: .00-1.33; response: -.20-1.00) demonstrated accurate classification to treatment response groups on the individual level.ConclusionsThis study demonstrated the applicability of the MAIA-2 questionnaire in MDD. The updated version may have led to reliability improvements regarding the revised scales, but subthreshold reliability was evident prior to treatment. The measure's dimensions were sensitive to change. MIDs were established that corresponded with antidepressive treatment outcomes. Our findings are consistent with a growing area of research which considers somatic feelings as key contributors to mental health.
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