Differentiating nicotine- versus schizophrenia-associated decreases of the α7 nicotinic acetylcholine receptor transcript, CHRFAM7A, in peripheral blood lymphocytes

Abstract

Nicotine addiction is prevalent in individuals with schizophrenia. Nicotine activation of nicotinic receptors (nAChRs) is time- and dose-dependent, but gene expression analyses often rely on qualitative self- or family-reported measures of smoking. We sought lymphocyte surrogates for cerebral alpha7-nAChR activity and tested if receptor transcription correlated with concurrently measured serum biomarkers for smoking [cotinine, C-reactive protein (CRP)]. PCR surveys to detect lymphocytic alpha7-related isoforms identified CHRFAM7A as the only consistently amplifiable transcript. In 20 smoking-matched people (n = 10 schizophrenia, n = 10 controls), we found significantly lower CHRFAM7A in cotinine and self-reported smokers versus nonsmokers (p <or= 0.001-0.03) and an inverse correlation of cotinine with CHRFAM7A (p <or= 0.04) in regression models. CHRFAM7A was not associated with diagnosis or CRP in any bi- or multi-variate analysis. Smoking-related CRP elevations only occurred in cotinine-based comparisons (p <or= 0.03), and not when smoking was self-reported. Including biochemical indicators of serum nicotine can help differentiate smoking- versus disease-associated changes in nAChR expression.