Lower β2*-Nicotinic Acetylcholine Receptor Availability in Smokers With Schizophrenia

Objective: There is a strong association between cigarette smoking and schizophrenia. Nicotine's actions in the brain are mediated through nicotinic acetylcholine receptors. Those containing alpha(4) and beta(2) subunits are the most abundant ones in the brain, have the highest affinity for nicotine, and are critical in mediating nicotine's reinforcing properties. Healthy tobacco smokers have significantly higher levels of beta(2)*-nicotinic acetylcholine receptors than do nonsmokers. However, in postmortem studies, smokers with schizophrenia do not show these higher levels. The purpose of this study was to measure beta(2)*-nicotinic acetylcholine receptors in vivo and to relate levels to concurrent behavioral measures of smoking and schizophrenia. Method: By using single-photon emission computed tomography with the beta(2)*-nicotinic acetylcholine receptor agonist radiotracer [I-123]5-IA-85380, the availability of receptors was measured in smokers with schizophrenia (11 men) and matched comparison smokers after 1 week of confirmed smoking abstinence. Results: Smokers with schizophrenia showed significantly lower (21%-26%) beta(2)*-nicotinic acetylcholine receptor availability relative to comparison smokers in the frontal cortex, parietal cortex, and thalamus (in descending order). There was a specific and robust negative correlation between regional beta(2)*-nicotinic acetylcholine receptor availability and negative symptoms. Conclusions: These are the first in vivo findings of lower beta(2)*-nicotinic acetylcholine receptor availability in smokers with schizophrenia. The relationship between beta(2)*-nicotinic acetylcholine receptor availability and negative symptoms may explain the high rates of smoking in schizophrenia and the relationship between smoking and negative symptoms. Findings support the development of medications targeting the beta(2)*-nicotinic acetylcholine receptor system for the treatment of negative symptoms.