Dementia rating and nicotinic receptor expression in the prefrontal cortex in schizophrenia

Background: The etiology of dementia that occurs in patients with schizophrenia is not well understood. Nicotinic acetylcholine receptors have been implicated in cognitive function, and deficits in these receptors have been reported in schizophrenia. Methods: The present study investigates possible associations of nicotinic receptor subunit expression in the dorsal lateral prefrontal cortex, an area known to be affected in schizophrenia, and dementia rating. Results: alpha7 immunoreactivity was reduced by 20% to 28% and [H-3]epibatidine binding was increased twofold in groups of patients with schizophrenia compared to normal control subjects matched for age, postmortem delay, and low levels of brain nicotine and cotinine. In contrast, no significant differences in alpha4, alpha3, or beta2 immunoreactivity or alpha7 messenger RNA expression were observed in schizophrenia patients compared with control subject values. Clinical dementia ratings in patients with schizophrenia were correlated with neither [H-3]epibatidine binding nor nicotinic receptor subunit expression. Conclusions: These data indicate no relationship between the trend for reduced neocortical alpha7 subunit protein expression in schizophrenia and dementia. Further investigations are required to establish whether the reduction in alpha7 protein in the dorsal lateral prefrontal cortex is associated with clinical features other than dementia in schizophrenia.