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 α7-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 α7-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 ≤ 0.001–0.03) and an inverse correlation of cotinine with CHRFAM7A (p ≤ 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 ≤ 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.
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The authors thank Vada and Theodore Stanley and the Stanley Medical Research Institute for their support. The authors also thank Ann Cusic for administrative assistance.
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Severance, E.G., Dickerson, F.B., Stallings, C.R. et al. Differentiating nicotine- versus schizophrenia-associated decreases of the α7 nicotinic acetylcholine receptor transcript, CHRFAM7A, in peripheral blood lymphocytes. J Neural Transm 116, 213–220 (2009). https://doi.org/10.1007/s00702-008-0164-y
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DOI: https://doi.org/10.1007/s00702-008-0164-y