Dataset Information

Association of circulating let-7b-5p with major depressive disorder: a nested case-control study.

ABSTRACT:

Background

Major depressive disorder (MDD) is one of the most common psychiatric disorders and is a great disease burden. However, its underlying pathophysiology and aetiology remain poorly understood. Available evidence suggests that circulating microRNAs (miRNAs) are associated with MDD, but it is still unknown whether miRNAs can predict subsequent incident MDD.

Methods

In this nested case-control study, a total of 104 individuals, who were free of MDD at baseline, from the Women's Health in Lund Area (WHILA) cohort were included. Among them, 52 individuals developed MDD (cases) during the 5 years follow-up and 52 individuals did not develop MDD (controls). Plasma expression levels of miR-17-5p, miR-134-5p, miR-144-5p, let-7b-5p and let-7c-5p at baseline were assessed using qRT-PCR. Logistic regression was used to estimate the odds of developing MDD among individuals with different levels of miRNA expression.

Results

Plasma expression levels of let-7b-5p were significantly lower (p = 0.02) at baseline in cases compared to controls. After adjustment for age and BMI, let-7b-5p was negatively associated with odds for developing MDD (OR = 0.33, p = 0.03, 95% CI = 0.12-0.91). Moreover, let-7b-5p expression levels showed a trend over time with larger differences between cases and controls for the earlier cases (MDD diagnosis <2 years from baseline) than MDD cases developed later (MDD diagnosis 2-5 years from baseline).

Conclusions

These findings show that lower plasma levels of let-7b-5p are associated with a higher future risk of MDD. Results need to be validated in a large cohort to examine its potential as a peripheral biomarker for MDD.

SUBMITTER: Roumans S

PROVIDER: S-EPMC8662878 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

Association of circulating let-7b-5p with major depressive disorder: a nested case-control study.

Roumans Sanne S Sundquist Kristina K Memon Ashfaque A AA Hedelius Anna A Sundquist Jan J Wang Xiao X

BMC psychiatry 20211209 1

<h4>Background</h4>Major depressive disorder (MDD) is one of the most common psychiatric disorders and is a great disease burden. However, its underlying pathophysiology and aetiology remain poorly understood. Available evidence suggests that circulating microRNAs (miRNAs) are associated with MDD, but it is still unknown whether miRNAs can predict subsequent incident MDD.<h4>Methods</h4>In this nested case-control study, a total of 104 individuals, who were free of MDD at baseline, from the Wome ...[more]

PMID: 34886843

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Project description:ObjectivesMajor depressive disorder (MDD) is often comorbid with other chronic and/or serious diseases. However, little is known about the prevalence of various diseases that are present before MDD onset. We examined the prevalence of all pre-existing diseases in the 12 months before an MDD diagnosis.DesignExploratory nested case-control study.SettingData, including diagnoses based on International Statistical Classification of Diseases and Related Health Problems, 10th revision codes, were from a Japanese health insurance database (JMDC).ParticipantsAdults newly diagnosed with MDD during 2015, 2016 or 2017 (but not the preceding year) (cases) were matched (exact) 1:10 to controls by age, sex, index date and working status.Primary and secondary outcome measuresThe primary outcome was the proportion of patients in each group with each pre-existing disease during the 12 months before the index date (ie, before MDD diagnosis in cases). Odds ratios (ORs) for onset of MDD were calculated for each pre-existing disease. A post hoc multivariate analysis examined interactions of metabolic risk factors (diabetes, hypertension, dyslipidaemia), psychiatric disorders (sleep disorders, psychiatric disorders other than depression) and MDD-related symptoms (headache, pain, autonomic nerve imbalance) on MDD diagnosis.ResultsThere were 13 420 cases and 134 200 controls (mean age 41.9 years; 66.5% male). The prevalence of almost all pre-existing diseases was higher in cases than in controls. The highest ORs (5.8-21.0) were for psychiatric diseases and sleep disorders. Insomnia (21.1% of patients; OR 8.7) and neurosis (9.7%; OR 10.6) were particularly prevalent in the case group. The odds of MDD increased in the presence of metabolic risk factors, psychiatric disorders and/or MDD-related symptoms.ConclusionsThere is a high prevalence of pre-existing diseases in Japanese patients who develop MDD compared with matched controls without MDD. These results suggest that patients with chronic and/or serious diseases should be actively monitored for depression.

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

Association of circulating let-7b-5p with major depressive disorder: a nested case-control study.

Background

Methods

Results

Conclusions

Publications

Association of circulating let-7b-5p with major depressive disorder: a nested case-control study.

Similar Datasets

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