Effects of varenicline on motor cortical plasticity in non-smokers with schizophrenia.
Nicotinic acetylcholine receptors (nAChR) have been implicated in the pathophysiology of schizophrenia, and deficits in this system may contribute to high rates of cigarette smoking in this population. nAChR stimulation may modulate neuroplasticity, or long-term potentiation (LTP), which is a key mediator of cognitive performance. Varenicline is a nAChR partial agonist that may improve cognitive deficits in both smokers and non-smokers with schizophrenia; however, the mechanism by which varenicline alters cognition in schizophrenia remains unclear. Thus, the aim of this randomized, double-blind, placebo-controlled, crossover study was to determine the effects of varenicline on LTP-like plasticity indexed through transcranial magnetic stimulation (TMS) in non-smokers with schizophrenia.



Varenicline (0.5mg BID × 5 doses) or placebo was administered to 9 non-smokers with schizophrenia and 10 non-smoker healthy subjects. LTP-like plasticity was induced by TMS and paired associative stimulation (PAS) at 0.1Hz to the left motor cortex and measured every 15min for two hours post-PAS.



There was a significant diagnosis × medication interaction on peak potentiation (F (3, 34)=6.04, p<0.02) and post-hoc analyses indicated that varenicline significantly increased LTP in schizophrenia and decreased LTP in healthy subjects.



These preliminary findings suggest that varenicline may produce differential effects in non-smoking schizophrenia compared to control subjects. Given the role of LTP in learning and memory, these observations may suggest the potential for varenicline in the treatment of cognitive deficits in patients with schizophrenia.
Schizophrenia Division, Centre for Addiction and Mental Health, Canada; Institute of Medical Science, Faculty of Medicine, University of Toronto, Canada.
Alanna C
AC
Bridgman
Schizophrenia Division, Centre for Addiction and Mental Health, Canada; Institute of Medical Science, Faculty of Medicine, University of Toronto, Canada; Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, Canada.
Mera S
MS
Barr
Institute of Medical Science, Faculty of Medicine, University of Toronto, Canada; Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, Canada.
Michelle S
MS
Goodman
Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, Canada.
Reza
R
Zomorrodi
Institute of Medical Science, Faculty of Medicine, University of Toronto, Canada; Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, Canada; Division of Geriatric Psychiatry, Centre for Addiction and Mental Health, Canada.
Tarek
T
Rajji
Institute of Medical Science, Faculty of Medicine, University of Toronto, Canada; Department of Family and Community Medicine, Faculty of Medicine, University of Toronto, Canada; Department of Pharmacology and Toxicology, University of Toronto, Canada.
Bernard
B
Le Foll
Institute of Medical Science, Faculty of Medicine, University of Toronto, Canada; Division of Neurology, Faculty of Medicine, University of Toronto, Canada.
Robert
R
Chen
Institute of Medical Science, Faculty of Medicine, University of Toronto, Canada; Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, Canada; Mood and Anxiety Division, Centre for Addiction and Mental Health, Canada.
Zafiris J
ZJ
Daskalakis
Schizophrenia Division, Centre for Addiction and Mental Health, Canada; Institute of Medical Science, Faculty of Medicine, University of Toronto, Canada; Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, Canada. Electronic address: tony.george@camh.ca.
Tony P
TP
George
D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004576:Electromyography; D019054:Evoked Potentials, Motor / Q000187:drug effects; D005260:Female; D006225:Hand / Q000503:physiopathology; D006801:Humans; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D009044:Motor Cortex / Q000187:drug effects* / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000503:physiopathology; D018722:Nicotinic Agonists / Q000009:adverse effects / Q000494:pharmacology*; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000503:physiopathology; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D050781:Transcranial Magnetic Stimulation; D000068580:Varenicline / Q000009:adverse effects / Q000494:pharmacology*
D018722:Nicotinic Agonists; D000068580:Varenicline
Long-term potentiation; Neuroplasticity; Nicotinic acetylcholine receptors; Transcranial magnetic stimulation