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Clozapine Prolongs Cortical Silent Period in Patients with Treatment-Resistant Schizophrenia

Atsuhiro Miyazawa1, Nobuhisa Kanahara1, Yusuke Nakata1

  • 1Miyazawa, MD, Nakata, MD, PhD, Atsushi Kimura, MD, PhD, Oda, MD, PhD, Iyo, MD, PhD, Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan. Kanahara, MD, PhD, Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan, Division of Medical Treatment and Rehabilitation, Center for Forensic Mental Health, Chiba University, Chiba, Japan. Kodama, MD, PhD, Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Hiroshi Kimura, MD, PhD, Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan, Department of Psychiatry, Gakuji-kai Kimura Hospital, Chiba, Japan, Department of Psychiatry, International University of Health and Welfare, Chiba, Japan. Watanabe, MD, PhD, Division of Medical Treatment and Rehabilitation, Center for Forensic Mental Health, Chiba University, Chiba, Japan, Department of Psychiatry, Gakuji-kai Kimura Hospital, Chiba, Japan.

Psychopharmacology Bulletin
|June 7, 2021
PubMed
Abstract

Insights

Clozapine treatment prolonged the cortical silent period (CSP) in patients with treatment-resistant schizophrenia, indicating enhanced gamma-aminobutyric acid (GABA)B receptor function. This suggests clozapine may improve patient function through GABAergic pathways.

Area of Science:

  • Neuroscience
  • Psychiatry
  • Pharmacology

Background:

  • Schizophrenia is associated with gamma-aminobutyric acid (GABA) system abnormalities.
  • Clozapine is effective for treatment-resistant schizophrenia (TRS), but its mechanisms are unclear.
  • GABA receptors are a potential target for clozapine's therapeutic effects.

Purpose of the Study:

  • To investigate the effect of clozapine on GABAergic function in patients with schizophrenia.
  • To compare GABAergic function in patients treated with clozapine versus other antipsychotics and healthy controls.

Main Methods:

  • Cortical silent period (CSP), a measure of GABAB receptor function, was assessed using transcranial magnetic stimulation.
  • CSP was measured in three groups: patients with TRS treated with clozapine (N=12), patients with TRS treated with other antipsychotics (N=25), and healthy controls (N=27).

Main Results:

  • Patients treated with clozapine exhibited a significantly longer CSP compared to the other two groups.
  • The CSP in patients treated with other antipsychotics was comparable to that of healthy subjects.
  • A positive correlation was observed between CSP duration and the Global Assessment of Function (GAF) in patients with TRS.

Conclusions:

  • Clozapine treatment prolongs the CSP, suggesting enhanced GABAB receptor-mediated neurotransmission.
  • These findings support the hypothesis that clozapine's efficacy in TRS may involve modulation of GABAergic pathways.
  • The positive correlation between CSP and GAF highlights the potential functional significance of clozapine's effects on GABA transmission.
Keywords:
GABAantipsychoticcortical inhibitiontranscranial magnetic stimulationtreatment-resistant

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