Karaçam Doğan Melike. Effects of clozapine on cortical inhibition. Hacettepe University Faculty of Medicine, Department of Psychiatry, Dissertation Thesis, Ankara, 2021. Preclinical and clinical studies reported cortical inhibition deficits in schizophrenia. Transcranial magnetic stimulation (TMS) is a commonly used noninvasive measurement method. There are few studies evaluating the effects of antipsychotics on cortical inhibition. The purpose of this study is to investigate the effects of 90-120 days of clozapine treatment on TMS parameters and and to compare them with healthy controls. Ten patients who were planned to initiate clozapine by their doctors were included in the study, and the follow-up of eight patients completed. Eight healthy controls matched with patients for age and sex were also included. Patients were assessed with Positive and Negative Syndrome Scale (PANSS), Thought and Language Disorder Scale (TALD), and World Health Organization Disability Assessment Scale-II (WHODAS-II) and cognitive tests; also resting motor threshold (RMT), cortical silent period (CSP), short interval intracortical inhibition (SICI), intracortical facilitation (ICF) and short latency afferent inhibition (SAI) were measured by TMS at the beginning and end of the treatment. TMS parameters were measured in the controls. At the beginning, there was a difference between the patients and controls in RMT, ICF and SAI, but at the end, only ICF was different. CSP was found to be prolonged compared to baseline. Stroop-2 and RAVLT-5 scores were lower, Stroop-4 scores were higher. No correlation was found between the change in CSP and the change in cognitive tests. Prolongation of CSP shows that clozapine is associated with an increase in cortical inhibition. This is the first study to investigate the effect of clozapine on SAI. It is also the first follow-up study to compare the effect of clozapine on cortical inhibition parameters with its effect on cognitive tests. We believe that our findings will contribute to the literature on the pathophysiology and treatment of schizophrenia, and further follow-up studies with larger sample sizes are required.
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