Neuropsychological deficits in nonsmokers with schizophrenia: effects of a nicotinic antagonist.
BACKGROUND
Biochemical, physiological and genetic evidence suggests dysregulation of central nicotinic acetylcholine receptor (nAChR) systems in schizophrenia, which may contribute to neuropsychological dysfunction and the high rates of smoking in this disorder. To evaluate the effects of nAChR blockade on neuropsychological performance in schizophrenia without the confounding effects of cigarette smoking, we compared neuropsychological performance in schizophrenia and healthy control nonsmokers after pre-treatment with the centrally-acting nAChR antagonist mecamylamine (MEC).


METHODS
Using a within-subjects, counterbalanced design, schizophrenia (n = 14) and control (n = 15) nonsmokers were pre-treated for 3 days with MEC (0.0, 5.0, and 10.0 mg/day). Subjects performed repeated neuropsychological assessments including visuospatial working memory (VSWM), Continuous Performance Test (CPT), Wisconsin Card Sorting Test (WCST), Word Serial Position Test (WSPT) and Stroop Color Word Test (SCWT) during three sequential test sessions per week over three test weeks.


RESULTS
We found significant main effects of schizophrenia diagnosis on: VSWM 30 and 60 delays (p's < 0.01), CPT (% Hit Rate, Reaction Time, Variability Index; p < 0.01 for all outcomes), WCST (p < 0.01 for all outcomes) and Word Serial Position Test (p < 0.01). However, there were no main effects of repeated test administration (Session) or MEC dose on any of these outcomes, and no significant 3-way (DiagnosisxSessionxMEC dose) interactions.


CONCLUSIONS
Our results suggest that there are a broad range of neuropsychological deficits in nonsmokers with schizophrenia. Furthermore, pretreatment with a centrally-acting nAChR antagonist did not alter neuropsychological performance in either nonsmoking patients with schizophrenia or controls.
Sacco
Kristi A
KA
Program for Research in Smokers with Mental Illness (PRISM), Yale University School of Medicine, New Haven, CT 06519, USA. kristi.sacco@yale.edu
Termine
Angelo
A
Dudas
Melissa M
MM
Seyal
Aisha A
AA
Allen
Taryn M
TM
Vessicchio
Jennifer C
JC
Wexler
Bruce E
BE
George
Tony P
TP