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Antidepressant-resistant depression is characterized by reduced short- and long-interval cortical inhibition

Published online by Cambridge University Press:  03 June 2019

Jia-Shyun Jeng
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
Cheng-Ta Li*
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan Institute of Brain Science and Brain Research Center, National Yang-Ming University, Taipei, Taiwan Institute of Cognitive Neuroscience, National Central University, Jhongli, Taiwan
Hui-Ching Lin
Affiliation:
Department and Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan
Shih-Jen Tsai
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan
Ya-Mei Bai
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan Institute of Brain Science and Brain Research Center, National Yang-Ming University, Taipei, Taiwan
Tung-Ping Su
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan Institute of Brain Science and Brain Research Center, National Yang-Ming University, Taipei, Taiwan Department of Psychiatry, Cheng-Hsin General Hospital, Taipei, Taiwan
Yu-Wen Chang
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
Chih-Ming Cheng
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan Institute of Brain Science and Brain Research Center, National Yang-Ming University, Taipei, Taiwan Taipei Veterans General Hospital Yuan Shan branch, Yilan, Taiwan
*
Author for correspondence: Cheng-Ta Li, E-mail: on5083@msn.com; ctli2@vghtpe.gov.tw

Abstract

Background

Major depressive disorder (MDD) is highly heterogeneous and can be classified as treatment-resistant depression (TRD) or antidepressant-responsive depression (non-TRD) based on patients' responses to antidepressant treatment. Methods for distinguishing between TRD and non-TRD are critical clinical concerns. Deficits of cortical inhibition (CI) have been reported to play an influential role in the pathophysiology of MDD. Whether TRD patients' CI is more impaired than that of non-TRD patients remains unclear.

Methods

Paired-pulse transcranial magnetic stimulation (ppTMS) was used to measure cortical inhibitory function including GABAA- and GABAB-receptor-related CI and cortical excitatory function including glutamate-receptor-related intracortical facilitation (ICF). We recruited 36 healthy controls (HC) and 36 patients with MDD (non-TRD, n = 16; TRD, n = 20). All participants received evaluations for depression severity and ppTMS examinations. Non-TRD patients received an additional ppTMS examination after 3 months of treatment with the SSRI escitalopram.

Results

Patients with TRD exhibited reduced short-interval intracortical inhibition (SICI) and long-interval intracortical inhibition (LICI), as shown by abnormally higher estimates, than those with non-TRD or HC (F = 11.030, p < 0.001; F = 10.309, p < 0.001, respectively). After an adequate trial of escitalopram treatment, the LICI of non-TRD reduced significantly (t = − 3.628, p < 0.001), whereas the ICF remained lower than that of HC and showed no difference from pretreatment non-TRD.

Conclusions

TRD was characterized by relatively reduced CI, including both GABAA- and GABAB-receptor-mediated neurons while non-TRD preserved partial CI. In non-TRD, SSRIs may mainly modulate GABAB-receptor-related LICI. Our findings revealed distinguishable features of CI in antidepressant-resistant and responsive major depression.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2019

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