title: In vivo evidence for β2 nicotinic acetylcholine receptor subunit upregulation in smokers as compared with nonsmokers with schizophrenia.
abstract: BACKGROUND
  Schizophrenia is associated with very high rates of tobacco smoking. The latter may be related to an attempt to self-medicate symptoms and/or to alterations in function of high-affinity β2-subunit-containing nicotinic acetylcholine receptors (β2*-nAChRs).
  
  
  METHODS
  Smoking and nonsmoking subjects with schizophrenia (n=31) and age-, smoking-, and sex-matched comparison subjects (n=31) participated in one [123I]5-IA-85380 single photon emission computed tomography scan to quantify β2*-nAChR availability. Psychiatric, cognitive, nicotine craving, and mood assessments were obtained during active smoking, as well as smoking abstinence.
  
  
  RESULTS
  There were no differences in smoking characteristics between smokers with and without schizophrenia. Subjects with schizophrenia had lower β2*-nAChR availability relative to comparison group, and nonsmokers had lower β2*-nAChR availability relative to smokers. However, there was no smoking by diagnosis interaction. Relative to nonsmokers with schizophrenia, smokers with schizophrenia had higher β2*-nAChR availability in limited brain regions. In smokers with schizophrenia, higher β2*-nAChR availability was associated with lower negative symptoms of schizophrenia and better performance on tests of executive control. Chronic exposure to antipsychotic drugs was not associated with changes in β2*-nAChR availability in schizophrenia.
  
  
  CONCLUSIONS
  Although subjects with schizophrenia have lower β2*-nAChR availability relative to comparison group, smokers with schizophrenia appear to upregulate in the cortical regions. Lower receptor availability in smokers with schizophrenia in the cortical regions is associated with a greater number of negative symptoms and worse performance on tests of executive function, suggesting smoking subjects with schizophrenia who upregulate to a lesser degree may be at risk for poorer outcomes.
authors.affiliation: Department of Psychiatry, School of Medicine, Yale University; Department of Psychiatry, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut. Electronic address: irina.esterlis@yale.edu.
authors.forename: Irina
authors.initials: I
authors.lastname: Esterlis
authors.affiliation: Department of Psychiatry, School of Medicine, Yale University; Department of Psychiatry, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: Mohini
authors.initials: M
authors.lastname: Ranganathan
authors.affiliation: Department of Psychiatry, School of Medicine, Yale University; Department of Psychiatry, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: Frederic
authors.initials: F
authors.lastname: Bois
authors.affiliation: Department of Psychiatry, School of Medicine, Yale University.
authors.forename: Brian
authors.initials: B
authors.lastname: Pittman
authors.affiliation: Department of Psychiatry, School of Medicine, Yale University.
authors.forename: Marina R
authors.initials: MR
authors.lastname: Picciotto
authors.affiliation: Department of Psychiatry, School of Medicine, Yale University.
authors.forename: Lara
authors.initials: L
authors.lastname: Shearer
authors.affiliation: Department of Psychiatry, School of Medicine, Yale University.
authors.forename: Alan
authors.initials: A
authors.lastname: Anticevic
authors.affiliation: Department of Psychiatry, School of Medicine, Yale University; Department of Psychiatry, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: Jon
authors.initials: J
authors.lastname: Carlson
authors.affiliation: Department of Psychiatry, School of Medicine, Yale University.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Niciu
authors.affiliation: Department of Psychiatry, School of Medicine, Yale University; Department of Psychiatry, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: Kelly P
authors.initials: KP
authors.lastname: Cosgrove
authors.affiliation: Department of Psychiatry, School of Medicine, Yale University; Department of Psychiatry, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: D Cyril
authors.initials: DC
authors.lastname: D'Souza
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D056344:Executive Function / Q000502:physiology; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D021122:Protein Subunits; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000378:metabolism*; D012565:Schizophrenic Psychology; D012907:Smoking / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon; D015854:Up-Regulation
chemical_list: D007457:Iodine Radioisotopes; D021122:Protein Subunits; D011978:Receptors, Nicotinic
keywords: Executive control; SPECT; negative symptoms; nicotinic acetylcholine receptors; psychosis; tobacco smoking