Dataset Information

Major depressive disorder and stroke risks: a 9-year follow-up population-based, matched cohort study.

ABSTRACT:

Background and purpose

Major depressive disorder (MDD) is characterized by recurrent depressive episodes and one of the treatment choices is antidepressants. Patients with MDD are at greater risk of developing major metabolic diseases that may in turn lead to stroke. Moreover, both depressive symptoms and taking antidepressant medications are associated with higher risk of stroke. However, whether and how clinical depression increases stroke risk remains an unanswered question. Our aim was to provide answers to this question.

Methods

A matched cohort study of 5015 subjects (1003 MDD patients and 4012 control subjects) was conducted using a nationwide database. Subjects were followed to a maximum of 9 years to determine rates of newly-developed strokes, and controls and MDD groups with different levels of antidepressant refractoriness were compared to determine the temporal relation between stroke and three major metabolic comorbidities (i.e., diabetes mellitus, hypertension and hyperlipidemia). The levels of depressive symptoms and the antidepressant medications before stroke onset were investigated.

Results

Patients with MDD had significantly higher rates of stroke (4.3% vs. 2.8%, p<0.05) during the follow-up. Mediation regression analyses revealed that the occurrence of stroke in the MDD subjects was significantly mediated by the development of major metabolic diseases. Greater severity of depression, but not greater use of antidepressants, preceded the occurrence of stroke.

Conclusions

A clinical diagnosis of major depression leads to stroke indirectly through more intense depressive symptoms and the development of major comorbidities.

SUBMITTER: Li CT

PROVIDER: S-EPMC3466174 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Major depressive disorder and stroke risks: a 9-year follow-up population-based, matched cohort study.

Li Cheng-Ta CT Bai Ya-Mei YM Tu Pei-Chi PC Lee Ying-Chiao YC Huang Yu-Lin YL Chen Tzeng-Ji TJ Chang Wen-Han WH Su Tung-Ping TP

PloS one 20121008 10

<h4>Background and purpose</h4>Major depressive disorder (MDD) is characterized by recurrent depressive episodes and one of the treatment choices is antidepressants. Patients with MDD are at greater risk of developing major metabolic diseases that may in turn lead to stroke. Moreover, both depressive symptoms and taking antidepressant medications are associated with higher risk of stroke. However, whether and how clinical depression increases stroke risk remains an unanswered question. Our aim w ...[more]

PMID: 23056466

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Project description:Background:Major depressive disorder (MDD) is associated with significant impairments in health-related quality of life (HRQoL) and everyday functioning. This cohort study investigated the long-term development of HRQoL in patients with MDD and its association with patient characteristics, including depressive symptom severity and cognitive symptoms. Methods:The Prospective Epidemiological Research on Functioning Outcomes Related to Major depressive disorder (PERFORM) study was a longitudinal cohort study conducted in 1,159 outpatients aged 18-65 years with MDD in France, Germany, Spain, Sweden, and the UK. The patients were either initiating antidepressant monotherapy or undergoing their first switch of antidepressant. HRQoL was assessed using the Medical Outcomes Study Short-Form 12-item Health Survey (SF-12) up to month 12 and the EuroQol Five Dimensions questionnaire up to month 24 (UK only). Depressive symptom severity was assessed up to month 24 by the patient-reported Patient Health Questionnaire and cognitive symptoms by the Perceived Deficit Questionnaire. Multivariate analyses were performed to identify patient characteristics associated with HRQoL. Results:Mental HRQoL was severely impaired at baseline versus normative data (mean [SD] SF-12 mental component summary [MCS], 26.5 [9.2]); mean (SD) physical component summary (PCS) total score was 45.2 (12.1). SF-12 MCS improved over 12 months of follow-up (38.7 [11.6] at month 12), while SF-12 PCS remained stable (45.3 [11.1]). At each assessment time point, there was a clear pattern of lower SF-12 MCS and PCS total score in patients experiencing greater cognitive problems. The mean EuroQol Five Dimensions questionnaire utility index score generally decreased (i.e., worsened) with increasing severity of cognitive and depressive symptoms at all time points up to 24 months. Multivariate analyses identified both depression severity and cognitive symptoms as strongly and significantly associated with poor HRQoL. Conclusion:These findings highlight the importance of recognizing and managing residual symptoms in patients with MDD, including the cognitive symptoms, to restore long-term psychosocial functioning.

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.

Dataset Information

Major depressive disorder and stroke risks: a 9-year follow-up population-based, matched cohort study.

Background and purpose

Methods

Results

Conclusions

Publications

Major depressive disorder and stroke risks: a 9-year follow-up population-based, matched cohort study.

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