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Michigan Biomarkers for Refractory Depression (Bluebird) metabolomics pilot study

ABSTRACT: The goal of the project is discovery of clinical useful biomarkers for treatment-resistant depression. All participants were undergoing electroconvulsive therapy (ECT) for treatment-resistant depression (major depressive disorder or bipolar disorder) in 2012-2014. All subjects were Caucasian except BB060, who was Asian. Samples were collected from each subject at baseline just before the first ECT treatment (Time Point T0) and approximately 3 weeks later just before the tenth ECT treatment (Time Point T2). Whole blood was drawn in the morning in a fasted state (at least 7 hours) through an intravenous catheter or butterfly needle into 6-mL EDTA tubes (Lavender Top, Becton Dickinson Vacutainer K2EDTA additive blood collection tube, part #367863) and transported to the processing lab at the Michigan Clinical Research Unit within 30 minutes. Plasma was isolated by centrifugation for 10 minutes at 2000G at 4C. Plasma from multiple tubes was pooled and aliquotted in 200 uL volumes into 2-mL screw-cap cryovials and frozen at -80C.

ORGANISM(S): Human Homo Sapiens

TISSUE(S): Blood

DISEASE(S): Depression

SUBMITTER: Maureen Kachman

PROVIDER: ST000775 | MetabolomicsWorkbench | Mon Jun 19 00:00:00 BST 2017

REPOSITORIES: MetabolomicsWorkbench

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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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Michigan Biomarkers for Refractory Depression (Bluebird) metabolomics pilot study

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