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Multiple risk factors predict recurrence of major depressive disorder in women.

ABSTRACT: BACKGROUND:It is difficult to predict recurrence of depressive episodes in patients with major depression (MD): evidence for many risk factors is inconsistent and general prediction algorithms are lacking. The aim of this study was to develop a prediction model for recurrence of depressive episodes in women using improved methodology. METHODS:We used prospective data from a general population sample of female twins with a last-year MD episode (n=194). A rich set of baseline predictors was analyzed with Cox proportional hazards regression subject to elastic net regularization to find a model predicting recurrence of depressive episodes. Prediction accuracy of the model was assessed in an independent test sample (n=133), which was limited by the unavailability of a number of key predictors. RESULTS:A wide variety of risk factors predicted recurrence of depressive episodes in women: depressive and anxiety symptoms during the index episode, the level of symptoms at the moment of interview, psychiatric and family history, early and recent adverse life events, being unmarried, and problems with friends and finances. Kaplan Meier estimated survival curves showed that the model differentiated between patients at higher and lower risk for recurrence; estimated areas under the curve were in the range of 0.61-0.79. LIMITATIONS:Despite our rich set of predictors, certain potentially relevant variables were not available, such as biological measures, chronic somatic diseases, and treatment status. CONCLUSIONS:Recurrence of episodes of MD in women is highly multifactorial. Future studies should take this into account for the development of clinically useful prediction algorithms.

SUBMITTER: van Loo HM

PROVIDER: S-EPMC4504430 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Multiple risk factors predict recurrence of major depressive disorder in women.

van Loo Hanna M HM Aggen Steven H SH Gardner Charles O CO Kendler Kenneth S KS

Journal of affective disorders 20150402

<h4>Background</h4>It is difficult to predict recurrence of depressive episodes in patients with major depression (MD): evidence for many risk factors is inconsistent and general prediction algorithms are lacking. The aim of this study was to develop a prediction model for recurrence of depressive episodes in women using improved methodology.<h4>Methods</h4>We used prospective data from a general population sample of female twins with a last-year MD episode (n=194). A rich set of baseline predic ...[more]

PMID: 25881281

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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.

Project description:BackgroundPrevious studies suggest that deficits in cognition may increase the risk of suicide. Our study aims to develop a machine learning (ML) algorithm-based suicide risk prediction model using cognition in patients with major depressive disorder (MDD).MethodsParticipants comprised 52 depressed suicide attempters (DSA) and 61 depressed non-suicide attempters (DNS), and 98 healthy controls (HC). All participants were required to complete a series of questionnaires, the Suicide Stroop Task (SST) and the Iowa Gambling Task (IGT). The performance in IGT was analyzed using repeated measures ANOVA. ML with extreme gradient boosting (XGBoost) classification algorithm and locally explanatory techniques assessed performance and relative importance of characteristics for predicting suicide attempts. Prediction performances were compared with the area under the curve (AUC), decision curve analysis (DCA), and net reclassification improvement (NRI).ResultsDSA and DNS preferred to select the card from disadvantageous decks (decks "A" + "B") under risky situation (p = 0.023) and showed a significantly poorer learning effect during the IGT (F = 2.331, p = 0.019) compared with HC. Performance of XGBoost model based on demographic and clinical characteristics was compared with that of the model created after adding cognition data (AUC, 0.779 vs. 0.819, p > 0.05). The net benefit of model was improved and cognition resulted in continuous reclassification improvement with NRI of 5.3%. Several clinical dimensions were significant predictors in the XGBoost classification algorithm.LimitationsA limited sample size and failure to include sufficient suicide risk factors in the predictive model.ConclusionThis study demonstrate that cognitive deficits may serve as an important risk factor to predict suicide attempts in patients with MDD. Combined with other demographic characteristics and attributes drawn from clinical questionnaires, cognitive function can improve the predictive effectiveness of the ML model. Additionally, explanatory ML models can help clinicians detect specific risk factors for each suicide attempter within MDD patients. These findings may be helpful for clinicians to detect those at high risk of suicide attempts quickly and accurately, and help them make proactive treatment decisions.

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Multiple risk factors predict recurrence of major depressive disorder in women.

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Multiple risk factors predict recurrence of major depressive disorder in women.

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