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Gene expression analysis in whole blood samples obtained from donors diagnosed with MDD compared to healthy controls

ABSTRACT: This study investigated gene expression changes in whole blood samples obtained from donors diagnosed with major depressive disorder (MDD) compared to healthy controls. Micro-array data were available from whole blood on patients with MDD (N=128, 64 with generalised anxiety disorder, diagnosed by the MINI questionnaire, and 64 without anxiety disorder) and healthy controls (N=64). RNA was isolated from all samples using the standard PAXgene protocol on the Qiagen Biorobot 8000. All samples gave good quality RNA, as assessed by Agilent Bioanalyser. The yield range was 0.86-15.05ug with an average of 6.25ug. Samples were then randomised into batches, with each batch containing a representative number of controls, depression with anxiety and depression without anxiety, and the same ratio of females to males (3:1). 50ng of RNA from each sample was converted to a biotin labeled cDNA probe using NuGEN SPIA amplification. The probes were then hybridized to Affymetrix U133_Plus2.0 Genechips.

ORGANISM(S): Homo sapiens

PROVIDER: GSE98793 | GEO | 2017/05/12

SECONDARY ACCESSION(S): PRJNA386248

REPOSITORIES: GEO

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Project description:Major depressive disorder (MDD) is the psychiatric disorder with the highest prevalence in the world. Pharmacological antidepressant treatment (AD), such as selective serotonin reuptake inhibitors [SSRI, i.e. fluoxetine (Flx)] is the first line of treatment for MDD. Despite its efficacy, lack of AD response occurs in numerous patients characterizing Difficult-to-treat Depression. ElectroConvulsive Therapy (ECT) is a highly effective treatment inducing rapid improvement in depressive symptoms and high remission rates of ~50–63% in patients with pharmaco-resistant depression. Nevertheless, the need to develop reliable treatment response predictors to guide personalized AD strategies and supplement clinical observation is becoming a pressing clinical objective. Here, we propose to establish a proteomic peripheral biomarkers signature of ECT response in an anxio/depressive animal model of non-response to AD. Using an emotionality score based on the analysis complementary behavioral tests of anxiety/depression (Elevated Plus Maze, Novelty Suppressed Feeding, Splash Test), we showed that a 4-week corticosterone treatment (35 μg/ml, Cort model) in C57BL/6JRj male mice induced an anxiety/depressive-like behavior. A 28-days chronic fluoxetine treatment (Flx, 18 mg/kg/day) reduced corticosterone-induced increase in emotional behavior. A 50% decrease in emotionality score threshold before and after Flx, was used to separate Flx-responding mice (Flx-R, n=18), or Flx non-responder mice (Flx-NR, n=7). Then, Flx-NR mice received 7 sessions of electroconvulsive seizure (ECS, equivalent to ECT in humans) and blood was collected before and after ECS treatment. Chronic ECS normalized the elevated emotionality observed in Flx-NR mice. Then, proteins were extracted from peripheral blood mononuclear cells (PBMCs) and isolated for proteomic analysis using a high-resolution MS Orbitrap. The proteomic analysis revealed a signature of 33 peripheral proteins associated with response to ECS (7 down- and 26 upregulated). These proteins were previously associated with mental disorders and involved in regulating pathways which participate to the depressive disorder etiology. remark for sample name : ECTR=Flx-NR-ES, C=cort/Veh, CFNR= Flx-NR

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Gene expression analysis in whole blood samples obtained from donors diagnosed with MDD compared to healthy controls

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