Cardiovascular biomarkers of response to accelerated low frequency repetitive transcranial magnetic stimulation in major depression

Abstract

Background and objective: Repetitive transcranial magnetic stimulation (rTMS) is an effective and safe treatment for major depressive disorder (MDD). rTMS is in need of a reliable biomarker of treatment response. High frequency (HF) dorsolateral prefrontal cortex (DLPFC) rTMS has been reported to induce significant changes in the cardiac activity of MDD patients. Low frequency DLPFC rTMS has many advantages over HF-DLPFC rTMS and thus this study aims to further investigate the effect of low frequency 1 Hz right hemisphere (R)-DLPFC rTMS on the cardiac activity of MDD patients, as well as the potential of using electrocardiogram (ECG) parameters as biomarkers of treatment outcome.

Methods: Baseline ECG sessions were performed for 19 MDD patients. All patients then underwent 40 sessions of accelerated 1 Hz R-DLPFC rTMS one week after the baseline session.

Results: Heart rate (HR) significantly decreased from the resting period to the first and third minute of the 1 Hz R-DLPFC rTMS period. Resting HR was found to have a significant negative association with treatment outcome. Prior to Bonferroni correction, HR during stimulation and the degree of rTMS-induced HR reduction were significantly negatively associated with treatment outcome. No significant changes were observed for the heart rate variability (HRV) parameters.

Limitations: Sample size (n = 19); the use of electroencephalography equipment for ECG; lack of respiration monitoring; relatively short recording duration for HRV parameters.

Conclusion: This novel study provides further preliminary evidence that ECG may be utilized as a biomarker of rTMS treatment response in MDD.

Trial registration: ClinicalTrials.gov Identifier: NCT04376697.

Keywords: Biomarkers; Electrocardiogram; Low frequency rTMS; Major depressive disorder.

Conflict of interest statement

Conflict of interest JZS, FM, KD, TR, RZ, MH, LF, HV do not report any conflict of interest. DMB receives research support from CIHR, NIH, Brain Canada and the Temerty Family through the CAMH Foundation and the Campbell Research Institute. He received research support and in-kind equipment support for an investigator-initiated study from Brainsway Ltd. and he has been the site principal investigator for sponsor-initiated studies for Brainsway Ltd. He also receives in-kind equipment support from Magventure for investigator-initiated studies. He received medication supplies for an investigator-initiated trial from Indivior. ZJD has received research and equipment in-kind support for an investigator-initiated study through Brainsway Inc. and Magventure Inc. His work has been supported by the Canadian Institutes of Health Research (CIHR), the National Institutes of Mental Health (NIMH), Brain Canada and the Temerty Family and Grant Family and through the Centre for Addiction and Mental Health (CAMH) Foundation and the Campbell Institute. JD has received research support from the Arrell Family Foundation, the Buchan Family Foundation, Brain Canada, the Canadian Biomarker Integration Network in Depression, the Canadian Institutes of Health Research (CIHR), the Klarman Family Foundation, NIH, the Ontario Brain Institute, the Toronto General and Western Hospital Foundation, and the Weston Family Foundation; he has received travel stipends from Lundbeck and ANT Neuro; he has served as an advisor for BrainCheck, Restorative Brain Clinics, and TMS Neuro Solutions. JPM reports research grants from the Brain & Behavior Research Foundation (BBRF) Young Investigator Award and the Réseau Québécois sur le Suicide, les troubles de l'Humeur et les troubles Associés (RQSHA) as well as salary support for his graduate studies from the Branch Out Neurological Foundation. JDG has received research support from the Labatt Family Network, the CAMH Discovery Fund, the University of Toronto EMHSeed program, and the Tri-Council Canada-UK AI Initiative.

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