Longitudinal effects of rTMS on neuroplasticity in chronic treatment-resistant depression

Iris Dalhuisen,Joey Bartholomeus,Indira Tendolkar,Alex De Bruijn,Eveline Ackermans,Lieke Martens,Jan Spijker,Peter Mulders,Philip Van Eijndhoven

doi:10.1007/s00406-020-01135-w

Abstract

Major depressive disorder (MDD) is amongst the most prevalent of psychiatric disorders. Unfortunately, a third of patients will not respond to conventional treatments and suffer from treatment-resistant depression (TRD). Repetitive transcranial magnetic stimulation (rTMS) has been proven effective in treating TRD. The research suggests that rTMS acts via neuroplastic effects on the brain, which can be measured by changes in hippocampal and amygdala volume as well as cortical thickness. This sham-controlled study investigates longitudinal effects of rTMS on the volumes of the hippocampus and amygdala and cortical thickness in patients with chronic TRD. 31 patients received 20 sessions of high-frequency rTMS (N = 15) or sham treatment (N = 16) over the left dorsolateral prefrontal cortex during 4 consecutive weeks. Using structural magnetic resonance imaging, we investigated longitudinal treatment effects on hippocampus and amygdala volume as well as thickness of the paralimbic cortex. We found no clinical differences between the active and sham rTMS group. Longitudinal changes in hippocampal and amygdala volume did not differ significantly, although males showed a significant decrease in left amygdala volume, irrespective of treatment group. Changes in cortical thickness of the paralimbic cortex differed significantly between the active and sham groups. Most notably, the increase in cortical thickness of the isthmus of the left cingulate gyrus was greater in the active as compared to the sham rTMS group. Our data suggest that rTMS can induce neuroplastic changes, particularly in cortical thickness, independent of treatment response. We also found longitudinal changes in amygdala volume in males. For clinical effects to follow these neuroplastic effects, more intensive rTMS treatment might be needed in chronically depressed patients.Trial registration number: ISRCTN 15535800, registered on 29-06-2017.

Highlights

Major depressive disorder (MDD) is a disabling psychiatric disorder affecting over 300 million people around the world
We studied the longitudinal effects of Repetitive transcranial magnetic stimulation (rTMS) on hippocampal and amygdala volumes, and thickness of the paralimbic cortex, using structural magnetic resonance imaging
Despite the absence of clinical effects, we identified neuroplastic changes in the cingulate cortex, which may indicate that a more intensive treatment protocol could lead to enhanced neuroplastic changes, which in turn could lead to better treatment response

Summary

Introduction

Major depressive disorder (MDD) is a disabling psychiatric disorder affecting over 300 million people around the world. Up to 35% of MDD patients do not respond sufficiently to first-line treatments with antidepressant medication or psychotherapy [2]. Patients with treatment-resistant depression (TRD) have a high risk for chronicity and often suffer from comorbid disorders and suicide attempts, emphasizing the need for more effective treatment options [3, 4]. From a neurobiological perspective, decreased neuroplasticity is thought to be the most important underlying mechanism to explain treatment resistance and chronicity [5, 6]. This is reflected on a macroscopic level by for example decreased hippocampal and amygdala volume

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