Oxolipidomics profile in major depressive disorder: Comparing remitters and non-remitters to repetitive transcranial magnetic stimulation treatment.

Hannah Stirton,Amir Ravandi,Benjamin P. Meek,Andrea L. Edel,Harold Aukema,Zahra Solati,Arun Surendran,Mandana Modirrousta,Zezhi Li

doi:10.1371/journal.pone.0246592

Abstract

BackgroundRepetitive Transcranial Magnetic Stimulation [rTMS] is increasingly being used to treat Major Depressive Disorder [MDD]. Given that not all patients respond to rTMS, it would be clinically useful to have reliable biomarkers that predict treatment response. Oxidized phosphatidylcholine [OxPC] and some oxylipins are important plasma biomarkers of oxidative stress and inflammation. Not only is depression associated with oxidative stress, but rTMS has been shown to have anti-oxidative effects.ObjectivesTo investigate whether plasma oxolipidomics profiles could predict treatment response in patients with treatment resistant MDD.MethodsFourty-eight patients undergoing rTMS treatment for MDD were recruited along with nine healthy control subjects. Plasma OxPCs and oxylipins were extracted and analyzed through high performance liquid chromatography coupled with mass spectrometry. Patients with a Hamilton Depression Rating Scale score [Ham-D] ≤7 post-treatment were defined as having entered remission.ResultsFifty-seven OxPC and 32 oxylipin species were identified in our subjects. MDD patients who entered remission following rTMS had significantly higher pre-rTMS levels of total and fragmented OxPCs compared to non-remitters and controls [one-way ANOVA, p<0.05]. However, no significant changes in OxPC levels were found as a result of rTMS, regardless of treatment response [p>0.05]. No differences in plasma oxylipins were found between remitters and non-remitters at baseline.ConclusionCertain categories of OxPCs may be useful predictive biomarkers for response to rTMS treatment in MDD. Given that elevated oxidized lipids may indicate higher levels of oxidative stress and inflammation in the brain, patients with this phenotype of depression may be more receptive to rTMS treatment.

Highlights

Major Depressive Disorder [MDD] is a debilitating psychiatric condition that has a lifetime prevalence of 20.6% [1]
MDD patients who entered remission following repetitive transcranial magnetic stimulation (rTMS) had significantly higher pre-rTMS levels of total and fragmented OxPCs compared to non-remitters and controls [one-way ANOVA, p
Given that elevated oxidized lipids may indicate higher levels of oxidative stress and inflammation in the brain, patients with this phenotype of depression may be more receptive to rTMS treatment

Summary

Introduction

Major Depressive Disorder [MDD] is a debilitating psychiatric condition that has a lifetime prevalence of 20.6% [1]. Reactive oxygen species [ROS] are one major source of oxidative stress, produced as by-products from normal cellular respiration [6]. Brain cells are highly vulnerable to oxidative stress because the brain is composed of at least 40% lipids, consumes 20% of total body oxygen, and has low anti-oxidant defences [4, 7,8,9]. Several studies have proposed that increased oxidative stress may be a contributing factor in the pathogenesis of MDD [10,11,12]. Patients with MDD have higher levels of certain oxidative stress biomarkers, including F2-isoprostanes and 8-OH 2-deoxyguanosine [8-OHdG] [13]. Repetitive Transcranial Magnetic Stimulation [rTMS] is increasingly being used to treat Major Depressive Disorder [MDD]. Is depression associated with oxidative stress, but rTMS has been shown to have anti-oxidative effects

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