Abstract

We investigated transcriptomic markers of late-onset major depressive disorder (LOD; onset age of first depressive episode ≥ 50 years) from the genes expressed in blood cells and identified state-dependent transcriptomic markers in these patients. We assessed the genes expressed in blood cells by microarray and found that the expression levels of 3,066 probes were state-dependently changed in the blood cells of patients with LOD. To select potential candidates from those probes, we assessed the genes expressed in the blood of an animal model of depression, ovariectomized female mice exposed to chronic ultra-mild stress, by microarray and cross-matched the differentially expressed genes between the patients and the model mice. We identified 14 differentially expressed genes that were similarly changed in both patients and the model mice. By assessing statistical significance using real-time quantitative PCR (RT-qPCR), the following 4 genes were selected as candidates: cell death-inducing DFFA-like effector c (CIDEC), ribonuclease 1 (RNASE1), solute carrier family 36 member-1 (SLC36A1), and serine/threonine/tyrosine interacting-like 1 (STYXL1). The discriminating ability of these 4 candidate genes was evaluated in an independent cohort that was validated. Among them, CIDEC showed the greatest discriminant validity (sensitivity 91.3% and specificity 87.5%). Thus, these 4 biomarkers should be helpful for properly diagnosing LOD.

Highlights

  • Major depressive disorder (MDD) is a highly prevalent psychiatric disorder that is associated with physical impairment, medical comorbidity, and mortality worldwide [1]

  • No significant difference was found in the mean age, sex composition, or mini-mental state examination (MMSE) scores between the depressed patients with late-onset major depressive disorder (LOD) (DPs; n = 10), the remitted patients with LOD (RMs; n = 10), and the healthy controls (HCs; n = 12)

  • The genome-wide expression of mRNA in blood cells was studied with microarray analysis, and 23,671 detected probes were scored with principal component analysis (PCA)

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Summary

Introduction

Major depressive disorder (MDD) is a highly prevalent psychiatric disorder that is associated with physical impairment, medical comorbidity, and mortality worldwide [1]. A recent study measuring the global burden of disease with disability-adjusted life-years suggested that a severe episode of MDD was a top contributor to disability among a variety of non-fatal consequences of disease and injury [2]. Current treatments are only partially effective, and patients have failed to respond to trials of existing antidepressant agents [3, 4]. Heterogeneous etiology and complicated pathophysiology likely contribute to such treatment resistance. It is possible that part of the ineffectiveness of antidepressant therapy for PLOS ONE | DOI:10.1371/journal.pone.0150262. It is possible that part of the ineffectiveness of antidepressant therapy for PLOS ONE | DOI:10.1371/journal.pone.0150262 February 29, 2016

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