Effects of cigarette smoking on spatial working memory and attentional deficits in schizophrenia: involvement of nicotinic receptor mechanisms.
BACKGROUND
Cigarette smoking rates in schizophrenia are higher than in the general population.


OBJECTIVE
To determine whether cigarette smoking modifies cognitive deficits in schizophrenia and to establish the role of nicotinic acetylcholine receptors (nAChRs) in mediating cigarette smoking-related cognitive enhancement.


METHODS
Neuropsychological assessments were performed at smoking baseline, after overnight abstinence, and after smoking reinstatement across 3 separate test weeks during which subjects were pretreated in a counterbalanced manner with the nonselective nAChR antagonist mecamylamine hydrochloride (0, 5, or 10 mg/d).


METHODS
Twenty-five smokers with schizophrenia and 25 control smokers.


METHODS
Outpatient mental health center.


METHODS
Visuospatial working memory (VSWM) and Continuous Performance Test (CPT) scores.


RESULTS
In smokers with schizophrenia and control smokers, overnight abstinence led to undetectable plasma nicotine levels and an increase in tobacco craving. While abstinence reduced CPT hit rate in both groups, VSWM was only impaired in smokers with schizophrenia. Smoking reinstatement reversed abstinence-induced cognitive impairment. Enhancement of VSWM and CPT performance by smoking reinstatement in smokers with schizophrenia, but not the subjective effects of smoking, was blocked by mecamylamine treatment.


CONCLUSIONS
Cigarette smoking may selectively enhance VSWM and attentional deficits in smokers with schizophrenia, which may depend on nAChR stimulation. These findings may have implications for understanding the high rates of smoking in schizophrenia and for developing pharmacotherapies for cognitive deficits and nicotine dependence in schizophrenia.
Sacco
Kristi A
KA
Program for Research in Smokers with Mental Illness, Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06519, USA.
Termine
Angelo
A
Seyal
Aisha
A
Dudas
Melissa M
MM
Vessicchio
Jennifer C
JC
Krishnan-Sarin
Suchitra
S
Jatlow
Peter I
PI
Wexler
Bruce E
BE
George
Tony P
TP
D000328:Adult; D001288:Attention / Q000187:drug effects*; D016739:Behavior, Addictive / Q000097:blood; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D003072:Cognition Disorders / Q000175:diagnosis* / Q000503:physiopathology / Q000517:prevention & control*; D015897:Comorbidity; D005260:Female; D006801:Humans; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology / Q000627:therapeutic use; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000175:diagnosis / Q000517:prevention & control*; D009483:Neuropsychological Tests; D009538:Nicotine / Q000009:adverse effects / Q000097:blood; D018733:Nicotinic Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*; D012559:Schizophrenia / Q000175:diagnosis* / Q000453:epidemiology* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology* / Q000523:psychology; D000074606:Smoking Prevention; D014029:Tobacco Use Disorder / Q000175:diagnosis / Q000503:physiopathology / Q000517:prevention & control
D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D008464:Mecamylamine; D009538:Nicotine