title: Differentiating nicotine- versus schizophrenia-associated decreases of the alpha7 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.
authors.affiliation: Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287-4933, USA. eseverance@jhmi.edu
authors.forename: Emily G
authors.initials: EG
authors.lastname: Severance
authors.forename: Faith B
authors.initials: FB
authors.lastname: Dickerson
authors.forename: Cassie R
authors.initials: CR
authors.lastname: Stallings
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Origoni
authors.forename: Anne
authors.initials: A
authors.lastname: Sullens
authors.forename: Eric T
authors.initials: ET
authors.lastname: Monson
authors.forename: Robert H
authors.initials: RH
authors.lastname: Yolken
mesh_terms: D002097:C-Reactive Protein / Q000032:analysis; D003367:Cotinine / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology; D020033:Protein Isoforms / Q000097:blood / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011978:Receptors, Nicotinic / Q000097:blood* / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000097:blood* / Q000235:genetics; D012907:Smoking / Q000097:blood* / Q000235:genetics; D014158:Transcription, Genetic; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579167:Chrna7 protein, human; D020033:Protein Isoforms; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine; D002097:C-Reactive Protein; D003367:Cotinine