Evidence for impaired cortical inhibition in schizophrenia using transcranial magnetic stimulation.
BACKGROUND
Cortical inhibition (CI) deficits have been proposed as a pathophysiologic mechanism in schizophrenia. This study employed 3 transcranial magnetic stimulation (TMS) paradigms to assess CI in patients with schizophrenia. Paired-pulse TMS involves stimulating with a lower-intensity pulse a few milliseconds before a higher-intensity pulse, thereby inhibiting the size of the motor evoked potential produced by the higher-intensity pulse. In the cortical silent period paradigm, inhibition is reflected by the silent period duration (ie, the duration of electromyographic activity cessation following a TMS-induced motor evoked potential). Transcallosal inhibition involves stimulation of the contralateral motor cortex several milliseconds prior to stimulation of the ipsilateral motor cortex, inhibiting the size of the motor evoked potential produced by ipsilateral stimulation.


METHODS
We measured CI using these 3 paradigms in 15 unmedicated patients with schizophrenia (14 medication-naive and 1 medication-free for longer than 1 year) (13 were in the transcallosal inhibition paradigm), 15 medicated patients with schizophrenia (11 taking olanzapine, 1 risperidone, 1 quetiapine, 1 methotrimeprazine + perphenazine, 1 quetiapine + loxapine), and 15 healthy controls.


RESULTS
Unmedicated patients demonstrated significant CI deficits compared with healthy controls across all inhibitory paradigms whereas medicated patients did not (at all inhibitory intervals, paired-pulse TMS: controls = 59.9%, medicated = 44.3%, unmedicated = 28.7%; cortical silent period: controls = 55.0 milliseconds, medicated = 60.4 milliseconds, unmedicated = 39.7 milliseconds; transcallosal inhibition: controls = 33.6%, medicated = 23.7%, unmedicated = 10.4%; P<.05).


CONCLUSIONS
These results suggest that schizophrenia is associated with deficits in CI and that antipsychotic medications may increase CI.
Daskalakis
Zafiris J
ZJ
Schizophrenia and Continuing Care Program, Centre for Addiction and Mental Health, Department of Psychiatry, Toronto Western General Hospital, University of Toronto, Ontario, Canada. Jeff_Daskalakis@camh.net
Christensen
Bruce K
BK
Chen
Robert
R
Fitzgerald
Paul B
PB
Zipursky
Robert B
RB
Kapur
Shitij
S
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects; D002540:Cerebral Cortex / Q000503:physiopathology*; D055590:Electromagnetic Phenomena / Q000379:methods*; D004576:Electromyography; D005260:Female; D006801:Humans; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology*; D012720:Severity of Illness Index
D014150:Antipsychotic Agents