In vivo evidence for ß2 nicotinic acetylcholine receptor subunit upregulation in smokers as compared with nonsmokers with schizophrenia.

BACKGROUND: Schizophrenia is associated with very high rates of tobacco smoking. The latter may be related to an attempt to self-medicate symptoms and/or to alterations in function of high-affinity ß2-subunit-containing nicotinic acetylcholine receptors (ß2*-nAChRs). METHODS: Smoking and nonsmoking subjects with schizophrenia (n=31) and age-, smoking-, and sex-matched comparison subjects (n=31) participated in one [123I]5-IA-85380 single photon emission computed tomography scan to quantify ß2*-nAChR availability. Psychiatric, cognitive, nicotine craving, and mood assessments were obtained during active smoking, as well as smoking abstinence. RESULTS: There were no differences in smoking characteristics between smokers with and without schizophrenia. Subjects with schizophrenia had lower ß2*-nAChR availability relative to comparison group, and nonsmokers had lower ß2*-nAChR availability relative to smokers. However, there was no smoking by diagnosis interaction. Relative to nonsmokers with schizophrenia, smokers with schizophrenia had higher ß2*-nAChR availability in limited brain regions. In smokers with schizophrenia, higher ß2*-nAChR availability was associated with lower negative symptoms of schizophrenia and better performance on tests of executive control. Chronic exposure to antipsychotic drugs was not associated with changes in ß2*-nAChR availability in schizophrenia. CONCLUSIONS: Although subjects with schizophrenia have lower ß2*-nAChR availability relative to comparison group, smokers with schizophrenia appear to upregulate in the cortical regions. Lower receptor availability in smokers with schizophrenia in the cortical regions is associated with a greater number of negative symptoms and worse performance on tests of executive function, suggesting smoking subjects with schizophrenia who upregulate to a lesser degree may be at risk for poorer outcomes.