title: Deficits in GABAA receptor function and working memory in non-smokers with schizophrenia.
abstract: BACKGROUND
  Although altered gamma-aminobutyric acid (GABA) neurotransmission has been implicated in the pathophysiology of schizophrenia, it is unclear whether the influence of GABA on working memory processes is confounded by nicotine use in this population. It is therefore crucial to evaluate working memory and its underlying mechanisms in non-smokers with schizophrenia to eliminate the confounding effects of nicotine on behavior and neurophysiology.
  
  
  METHODS
  In this cross-sectional study, working memory was assessed using the verbal N-back task, while GABAergic function was assessed through motor cortical inhibition using single and paired-pulse transcranial magnetic stimulation (TMS) to the left primary motor cortex in 11 non-smokers with schizophrenia and 13 non-smoker healthy subjects.
  
  
  RESULTS
  Similar to previously published studies, working memory performance was significantly impaired in the 3-back condition in patients with schizophrenia compared to healthy subjects (p=0.036). In addition, GABAA receptor function was significantly reduced in schizophrenia as assessed by short interval cortical inhibition (SICI) (p=0.005). A positive correlation was found between GABAA inhibition and working memory performance on the 3-back task (r(23)=0.55, p=0.006), suggesting that greater GABAA inhibition is associated with better performance on tasks of working memory.
  
  
  CONCLUSIONS
  Our findings highlight the role of GABAA receptor dysfunction in working memory and the pathophysiology of schizophrenia, and may represent a selective characteristic of schizophrenia. Moreover, these findings suggest a potential therapeutic role for targeting GABA receptor activity to improve cognition and quality of life in patients with schizophrenia.
authors.affiliation: Schizophrenia Division, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada; Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, 1001 Queen Street West, Toronto, ON M6J 1H4, Canada.
authors.forename: Alanna C
authors.initials: AC
authors.lastname: Bridgman
authors.affiliation: Schizophrenia Division, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada; Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, 250 College Street, Toronto, ON M5T 1R8, Canada; Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, 1001 Queen Street West, Toronto, ON M6J 1H4, Canada. Electronic address: mera.barr@camh.ca.
authors.forename: Mera S
authors.initials: MS
authors.lastname: Barr
authors.affiliation: Schizophrenia Division, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada; Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, 1001 Queen Street West, Toronto, ON M6J 1H4, Canada.
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Goodman
authors.affiliation: Division of Neurology, Department of Medicine, University of Toronto, 399 Bathurst Street, Toronto, ON M5T 2S8, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Chen
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, 1001 Queen Street West, Toronto, ON M6J 1H4, Canada; Division of Geriatric Psychiatry, Department of Psychiatry, University of Toronto, 250 College Street, Toronto, ON M5T 1R8, Canada.
authors.forename: Tarek K
authors.initials: TK
authors.lastname: Rajji
authors.affiliation: Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, 250 College Street, Toronto, ON M5T 1R8, Canada; Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, 1001 Queen Street West, Toronto, ON M6J 1H4, Canada.
authors.forename: Zafiris J
authors.initials: ZJ
authors.lastname: Daskalakis
authors.affiliation: Schizophrenia Division, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada; Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, 250 College Street, Toronto, ON M5T 1R8, Canada.
authors.forename: Tony P
authors.initials: TP
authors.lastname: George
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D003430:Cross-Sectional Studies; D004576:Electromyography; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000209:etiology*; D008570:Memory, Short-Term / Q000502:physiology*; D008875:Middle Aged; D009433:Neural Inhibition / Q000502:physiology*; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D011930:Reaction Time / Q000502:physiology; D018079:Receptors, GABA / Q000172:deficiency*; D012559:Schizophrenia / Q000150:complications*; D050781:Transcranial Magnetic Stimulation; D055815:Young Adult
chemical_list: D018079:Receptors, GABA
keywords: Cortical inhibition; Gamma-aminobutyric acid; N-back task; Transcranial magnetic stimulation