Neuroinflammatory Alterations in Treatment‐Resistant Depression Secondary to Long COVID by Repetitive Transcranial Magnetic Stimulation (rTMS): A Case Report
Publication: Psychiatric Research and Clinical Practice
To the Editor:
COVID‐19 infection leads to various symptoms such as fatigue, difficulty concentrating, memory loss, anxiety, and depressed mood (1). We report the first case to our knowledge of a patient with treatment‐resistant depression secondary to COVID‐19 infection who was treated with repetitive transcranial magnetic stimulation (rTMS) and present neuroinflammatory alterations revealed by positron emission tomography (PET).
A 39‐year‐old female, without a history of SARS‐COV‐2 vaccination nor depression, had contracted the COVID‐19 2 years ago. One year later, she had no core depressive symptoms such as depressed mood or loss of interest but went to outpatient clinics because of memory loss and severe fatigue. Despite treatments, her symptoms persisted for more than a year, and furthermore, she gradually presented with depressed mood, loss of pleasure, and difficulty concentrating. Diagnosed with depression, she did not respond to antidepressants including venlafaxine 150 mg/day. She came to our hospital for rTMS treatments. No structural abnormalities were observed on head magnetic resonance imaging. rTMS was administered over the left prefrontal cortex using the NeuroStar system (Neuronetics) at a frequency of 10 Hz with 120% motor threshold. She received 29 sessions over 6 weeks. No adverse events were observed. After the treatments, depressive symptoms with Hamilton Rating Scale for Depression‐17 scores improved from 20 to 7. A PET scan utilizing the translocator protein ligand [11C] DAA1106 (2) was performed before and after rTMS, which demonstrated that the standardized uptake value ratio of the neuroinflammatory marker [11C] DAA1106 was reduced in the whole brain (see Figure S1 and Table S1 in Online Supplement). The observed changes in each volume of interest ranged from 11.0% to 22.9%.
rTMS is shown to be effective in patients with treatment‐resistant depression (3). The findings suggest that rTMS may have anti‐neuroinflammatory effects in improving depression, which is consistent with the microglial inflammatory hypothesis of depression (4). Microglial hyperactivation has been shown to be associated with persistent depressive and cognitive symptoms (5), raising the possibility that some symptoms secondary to COVID‐19 infection and subsets of treatment‐resistant depression may share a common pathophysiology. Further investigation is needed to confirm the reproducibility of the findings and elucidate the underlying mechanisms in a well‐designed study.
Footnote
Dr. Yamazaki received personal fees from Inter Reha Co., Ltd., Dr. Matsuda received speaker's honoraria from Lundbeck Japan K.K., Sumitomo Pharma Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., and Viatris Inc. Dr. Noda has received speaker's honoraria from Sumitomo Pharma Co., Ltd. and Takeda Pharmaceutical Co. Ltd., Viatris Inc. and research grants from Inter Reha Co., Ltd., Dr Watanabe received grants from Daiichi Sankyo, Eisai, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, MSD, Otsuka Pharmaceutical, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, speaker's honoraria from Boehringer Ingelheim, Eisai, Janssen Pharmaceutical, Kyowa Pharmaceutical, Lundbeck Japan, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, MSD, Otsuka, Pharmaceutical, Shionogi, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, Viatris, and consulting fees from Boehringer Ingelheim, Daiichi Sankyo, Eisai, Janssen Pharmaceutical, Kyowa Pharmaceutical, Lundbeck Japan, Luye Pharma, Mitsubishi Tanabe Pharma, Otsuka Pharmaceutical, Sumitomo Dainippon Pharma, Taisho Toyama Pharmaceutical, Takeda Pharmaceutical, Viatris, Dr. Kito received speaker honoraria from Inter Reha Co., Ltd., Lundbeck Japan K.K., Sumitomo Pharma Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., and Viatris Inc.; consultant fees from Kyowa Pharmaceutical Industry Co., Ltd., Teijin Pharma Ltd., and Inter Reha Co., Ltd.; and research grants from Teijin Pharma Ltd., Dr. Igarashi, Dr. Okita and Dr. Hayashi have no COI to disclose.
Supplementary Material
REFERENCES
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Received: 11 October 2023
Revision received: 19 January 2024
Accepted: 23 January 2024
Published online: 1 April 2024
Published in print: Summer 2024
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