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

Jia Shyun Jeng*, Cheng Ta Li, Cheng Ta Li, Cheng Ta Li, Cheng Ta Li, Hui Ching Lin, Shih Jen Tsai, Shih Jen Tsai, Ya Mei Bai, Ya Mei Bai, Ya Mei Bai, Tung Ping Su, Tung Ping Su, Tung Ping Su, Tung Ping Su, Yu Wen Chang, Chih Ming Cheng, Chih Ming Cheng, Chih Ming Cheng

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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.

Original languageEnglish
Pages (from-to)1285-1291
Number of pages7
JournalPsychological Medicine
Issue number8
StatePublished - 1 Jun 2020


  • Antidepressant
  • LICI
  • paired-pulse transcranial magnetic stimulation (ppTMS)
  • SICI
  • SSRI
  • treatment-resistant depression (TRD)


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