Effect of repetitive Transcranial Magnetic Stimulation on a patient with major depressive disorder: changes of serum neurotophins levels

Introduction: While the antidepressant potential of repetitive transcranial magnetic stimulation (rTMS) is widely recognized [1], the impact on neurotrophins related to major depressive disorder (MDD) has not been fully investigated in humans. [2]. We probed rTMS on refractory depression and serum levels of some neurotrophic factors. Materials / Methods: A 41-years old MDD patient underwent TMS-Motor Evoked Potentials (MEPs) from the right first dorsal interosseous muscle with a figureof- eight coil, at baseline and after 2 weeks of high-frequency (10 Hz) rTMS at 120% of resting motor threshold over the left dorsolateral prefrontal cortex. Serum brain-derived growth factor (BDNF), vascular endothelial growth factor (VEGF), and Endothelin-1 were measured by Enzyme-Linked Immunosorbent Assay. Mouse monoclonal specific antibodies were used for detection, followed by horseradish peroxidase-conjugated goat anti-mouse IgG secondary antibody and using enhanced Western Lighting Chemiluminescence Reagent Plus. Changes in protein levels were then evaluated by imaging and densitometric analyses. The Ethics Committee of the â€oeAzienda Ospedaliero-Universitaria Policlinico-Vittorio Emanuele†, Catania (Italy), approved the study (N. 9/2018/PO). Results: Clinical improvement of depression was observed. Compared to baseline, MEPs amplitude increased by 54%, central motor conduction time decreased by 32%, and cortical silent period shortened by 12%. BDNF and VEGF significantly reduced by 20% and 18%, respectively (Figures), while Endothelin-1 was unchanged.Figures Discussion: A more excitable motor cortex and cortico-spinal tract was found, supporting the hypothesis of left-sided frontal hypoexcitability in MDD and the role of rTMS in balancing this asymmetry [1]. Several studies demonstrated an increase of VEGF in depressed patients [3], therefore its decrease after rTMS can predict treatment response, possibly due to changes in tissue secretion or blood-brain barrier permeability. Although drugs and electroconvulsive therapy can increase BDNF in depression, a recent meta-analysis showed that rTMS does not increase peripheral level [4]. Therefore, its suitability as an index of antidepressant response and neuroprotective factor requires further understanding [5,6]. Conclusions: Though obtained from a single patient, neurotrophins are involved in the pathophysiology of depression and antidepressant effect of rTMS. Future trials with homogenous populations, wider neurotrophins dosages, randomized controlled protocols, and follow-up assessments are needed. Objectives: rTMS feasibly explores cortical circuit neuroplasticity and neurochemical pathways in mood disorders. This intervention led to modulation of VEGF and BDNF, although the involvement of Endothelin-1 cannot be excluded. References: [1] Spampinato C, et al. 2013 [2] Haase J, Brown E. 2015 [3] Clark-Raymond A, et al. 2017 [4] Brunoni AR, et al. 2015 [5] Lange C, et al. 2016 [6] Shim JW, Madsen JR. 2018