title: Evidence for inhibitory deficits in the prefrontal cortex in schizophrenia.
abstract: Abnormal gamma-aminobutyric acid inhibitory neurotransmission is a key pathophysiological mechanism underlying schizophrenia. Transcranial magnetic stimulation can be combined with electroencephalography to index long-interval cortical inhibition, a measure of GABAergic receptor-mediated inhibitory neurotransmission from the frontal and motor cortex. In previous studies we have reported that schizophrenia is associated with inhibitory deficits in the dorsolateral prefrontal cortex compared to healthy subjects and patients with bipolar disorder. The main objective of the current study was to replicate and extend these initial findings by evaluating long-interval cortical inhibition from the dorsolateral prefrontal cortex in patients with schizophrenia compared to patients with obsessive-compulsive disorder. A total of 111 participants were assessed: 38 patients with schizophrenia (average age: 35.71 years, 25 males, 13 females), 27 patients with obsessive-compulsive disorder (average age: 36.15 years, 11 males, 16 females) and 46 healthy subjects (average age: 33.63 years, 23 females, 23 males). Long-interval cortical inhibition was measured from the dorsolateral prefrontal cortex and motor cortex through combined transcranial magnetic stimulation and electroencephalography. In the dorsolateral prefrontal cortex, long-interval cortical inhibition was significantly reduced in patients with schizophrenia compared to healthy subjects (P = 0.004) and not significantly different between patients with obsessive-compulsive disorder and healthy subjects (P = 0.5445). Long-interval cortical inhibition deficits in the dorsolateral prefrontal cortex were also significantly greater in patients with schizophrenia compared to patients with obsessive-compulsive disorder (P = 0.0465). There were no significant differences in long-interval cortical inhibition across all three groups in the motor cortex. These results demonstrate that long-interval cortical inhibition deficits in the dorsolateral prefrontal cortex are specific to patients with schizophrenia and are not a generalized deficit that is shared by disorders of severe psychopathology.
authors.affiliation: 1 Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Natasha
authors.initials: N
authors.lastname: Radhu
authors.affiliation: 1 Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Luis
authors.initials: L
authors.lastname: Garcia Dominguez
authors.affiliation: 1 Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Faranak
authors.initials: F
authors.lastname: Farzan
authors.affiliation: 2 Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Richter
authors.affiliation: 1 Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Mawahib O
authors.initials: MO
authors.lastname: Semeralul
authors.affiliation: 3 Division of Neurology, Toronto Western Research Institute, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Chen
authors.affiliation: 4 Monash Alfred Psychiatry Research Centre, The Alfred and Monash University Central Clinical School, Victoria, Australia.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Fitzgerald
authors.affiliation: 1 Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada Jeff.Daskalakis@camh.ca.
authors.forename: Zafiris J
authors.initials: ZJ
authors.lastname: Daskalakis
mesh_terms: D000328:Adult; D019412:Anatomy, Cross-Sectional; D014150:Antipsychotic Agents / Q000627:therapeutic use; D004569:Electroencephalography; D004576:Electromyography; D005260:Female; D006801:Humans; D007266:Inhibition, Psychological; D008297:Male; D009044:Motor Cortex / Q000473:pathology; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D017397:Prefrontal Cortex / Q000503:physiopathology*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy / Q000473:pathology*; D012565:Schizophrenic Psychology; D050781:Transcranial Magnetic Stimulation
chemical_list: D014150:Antipsychotic Agents
keywords: coritcal inhibition; dorsolateral prefrontal cortex; electroencephalography; gamma oscillations; obsessive-compulsive disorder; schizophrenia; transcranial magnetic stimulation