title: Nicotinic acetylcholine receptor expression on B-lymphoblasts of healthy versus schizophrenic subjects stratified for smoking: [3H]-nicotine binding is decreased in schizophrenia and correlates with negative symptoms.
abstract: Heavy smoking and schizophrenia are diversely associated with nicotinic acetylcholine receptor expression, as was shown for brain and lymphocytes. Most studies so far have not systematically differentiated between schizophrenia smokers and non-smokers and were confined either to in vivo or post-mortem study approaches. In order to avoid variable in vivo influences or post-mortem bias, we used stably transformed B-lymphoblast cultures derived from healthy and schizophrenia subjects stratified for smoking versus non-smoking in order to differentiate these clinical conditions with regard to nicotinic acetylcholine receptor expression and regulation. Receptor quantities were measured using [(3)H]-nicotine and [(3)H]-epibatidine binding. At baseline, [(3)H]-nicotine binding was not statistically different between healthy smokers and never-smokers (1.59 ± 0.73 vs. 1.26 ± 0.91 fmol/10(6) cells), while it was reduced in schizophrenia smokers compared to healthy smokers (1.05 ± 0.69 fmol vs. 1.44 ± 0.84/10(6) cells, P = 0.01). In schizophrenia, baseline [(3)H]-nicotine correlated inversely with higher PANSS negative subscale scores. After long-term nicotine incubation (1 μM), [3H]-nicotine binding increased in the group of schizophrenia smokers only (from 1.05 ± 0.69 to 1.54 ± 0.77 fmol/106 cells, P = 0.013), while [(3)H]-epibatidine binding decreased in this group (4.52 ± 1.52 to 3.82 ± 1.38 fmol/10(6) cells, P = 0.038). Our data are in further support of a decrease of nicotinic acetylcholine receptor expression in schizophrenia linked to negative psychotic symptoms, which may be counter-regulated by nicotine exposure.
authors.affiliation: Department of Psychiatry and Psychotherapy, Heinrich-Heine-University Duesseldorf, 40620 Duesseldorf, Germany. christian.luckhaus@lvr.de
authors.forename: Christian
authors.initials: C
authors.lastname: Luckhaus
authors.forename: Uwe
authors.initials: U
authors.lastname: Henning
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrea
authors.forename: Francesco
authors.initials: F
authors.lastname: Musso
authors.forename: Arian
authors.initials: A
authors.lastname: Mobascher
authors.forename: Georg
authors.initials: G
authors.lastname: Winterer
mesh_terms: D000328:Adult; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D061251:Primary Cell Culture; D011978:Receptors, Nicotinic / Q000096:biosynthesis*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D012907:Smoking / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: D011978:Receptors, Nicotinic; D009538:Nicotine