Cigarette smoking increases cholinergic activity in the central nervous system and, as a result, may temporarily enhance certain cognitive functions, particularly those related to selective attention, attentional vigilance, the response components of rapid information processing, and effortful/controlled memory processes. The prevalence of cigarette smoking among patients with schizophrenia is high (74%-92%), raising the possibility that cigarette smoking is an adaptive response in these patients, rewarding for its ability to induce neurochemically-based, transient cognitive improvements. This project will test the relation between plasma cholinergic levels and the above cognitive functions. Cholinergic levels and cognitive performance will be observed under conditions of recent/acute cigarette smoking and recent smoking abstinence (12 hrs.) in a sample of moderate (n=15) and heavy (n=15) smokers who suffer from chronic schizophrenia. Non-smoking chronic schizophrenic patients (n=15) will serve as controls to estimate cognitive fluctuations independent of smoking Condition (acute/abstinent). A three group repeated measures design will be used (n=45). All patient/subjects will meet DSM-III-R criteria for chronic schizophrenia, be matched by age, gender and duration of illness, and be on a verified, stable haloperidol regimen. Data on the primary independent variable (plasma muscarinic receptor binding as an index of cholinergic activity) and dependent variable (cognitive performance) will be collected under each Smoking Condition. Heart rate monitoring will verify current smoking status (heart rate acceleration/deceleration associated with acute/abstinence conditions, respectively). Plasma haloperidol, nicotine, and cotinine levels will verify medication metabolism and recent smoking intensity. A smoking induced, cholinergically-driven enhancement of cognitive performance is hypothesized.
