Elucidation of the pathophysiology of prefrontal cortex in patients with treatment-resistant depression using transcranial magnetic stimulation neurophysiology

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K15375
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Keio University
• Principal Investigator: NODA Yoshihiro 慶應義塾大学, 医学部(信濃町), 特任准教授 (20807226)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 治療抵抗性うつ病 / 経頭蓋磁気刺激法 / 高精度脳波計測 / TMS-EEG法 / 神経可塑性

Outline of Final Research Achievements

In this study, 30 patients with medication-resistant depression were strictly enrolled in neurophysiological experiments using TMS combined with high-resolution EEG. In addition, age- and sex-matched 30 healthy controls with depression were recruited and TMS-EEG experiments were conducted. Specifically, GABA(A) receptor- mediated neurophysiological function, glutamate NMDA receptor-mediated neurophysiological function, and neuroplasticity in the dorsolateral prefrontal cortex (DLPFC) were measured with combined TMS-EEG method by applying short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), and paired associative stimulation (PAS), respectively. As a result, it was suggested that glutamatergic excitatory function as indexed by ICF may be relatively elevated and neuroplastic function as indexed by PAS may be decreased in patients with treatment-resistant depression compared with healthy controls in the DLPFC.

Free Research Field

臨床神経生理学

Academic Significance and Societal Importance of the Research Achievements

治療抵抗性うつ病は、心理・社会・経済的損失が大きい病態群であるため、本病態の適切な診断と治療は当事者の社会機能の維持・社会復帰支援に貢献する可能性が極めて高い。今後はうつ病患者の前頭前野における神経可塑性を指標に層別化できるかどうかを評価していく方針である。本研究の知見や方法論を他の精神科的状態像にも応用することで、精神科臨床におけるより客観的な生物学的診断補助、精神科健診システムの開発、さらには神経生理指標を治療ターゲットとした新規rTMS療法の開発にも繋げてゆきたい。