Differentiating nicotine- versus schizophrenia-associated decreases of the alpha7 nicotinic acetylcholine receptor transcript, CHRFAM7A, in peripheral blood lymphocytes.

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.