title: Lower ß2*-nicotinic acetylcholine receptor availability in smokers with schizophrenia.
abstract: OBJECTIVE
  There is a strong association between cigarette smoking and schizophrenia. Nicotine's actions in the brain are mediated through nicotinic acetylcholine receptors. Those containing α(4) and β(2) subunits are the most abundant ones in the brain, have the highest affinity for nicotine, and are critical in mediating nicotine's reinforcing properties. Healthy tobacco smokers have significantly higher levels of β(2)*-nicotinic acetylcholine receptors than do nonsmokers. However, in postmortem studies, smokers with schizophrenia do not show these higher levels. The purpose of this study was to measure β(2)*-nicotinic acetylcholine receptors in vivo and to relate levels to concurrent behavioral measures of smoking and schizophrenia.
  
  
  METHODS
  By using single-photon emission computed tomography with the β(2)*-nicotinic acetylcholine receptor agonist radiotracer [(123)I]5-IA-85380, the availability of receptors was measured in smokers with schizophrenia (11 men) and matched comparison smokers after 1 week of confirmed smoking abstinence.
  
  
  RESULTS
  Smokers with schizophrenia showed significantly lower (21%-26%) β(2)*-nicotinic acetylcholine receptor availability relative to comparison smokers in the frontal cortex, parietal cortex, and thalamus (in descending order). There was a specific and robust negative correlation between regional β(2)*-nicotinic acetylcholine receptor availability and negative symptoms.
  
  
  CONCLUSIONS
  These are the first in vivo findings of lower β(2)*-nicotinic acetylcholine receptor availability in smokers with schizophrenia. The relationship between β(2)*-nicotinic acetylcholine receptor availability and negative symptoms may explain the high rates of smoking in schizophrenia and the relationship between smoking and negative symptoms. Findings support the development of medications targeting the β(2)*-nicotinic acetylcholine receptor system for the treatment of negative symptoms.
authors.affiliation: Psychiatry Service, VA Connecticut Healthcare System, West Haven, USA. deepak.dsouza@yale.edu
authors.forename: Deepak Cyril
authors.initials: DC
authors.lastname: D'Souza
authors.forename: Irina
authors.initials: I
authors.lastname: Esterlis
authors.forename: Michelle
authors.initials: M
authors.lastname: Carbuto
authors.forename: Maegan
authors.initials: M
authors.lastname: Krasenics
authors.forename: John
authors.initials: J
authors.lastname: Seibyl
authors.forename: Frederic
authors.initials: F
authors.lastname: Bois
authors.forename: Brian
authors.initials: B
authors.lastname: Pittman
authors.forename: Mohini
authors.initials: M
authors.lastname: Ranganathan
authors.forename: Kelly
authors.initials: K
authors.lastname: Cosgrove
authors.forename: Julie
authors.initials: J
authors.lastname: Staley
mesh_terms: D000328:Adult; D001923:Brain Chemistry / Q000502:physiology; D005260:Female; D005625:Frontal Lobe / Q000737:chemistry / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010296:Parietal Lobe / Q000737:chemistry / Q000503:physiopathology; D011978:Receptors, Nicotinic / Q000032:analysis* / Q000502:physiology; D012559:Schizophrenia / Q000150:complications / Q000503:physiopathology*; D012907:Smoking / Q000503:physiopathology* / Q000523:psychology; D016540:Smoking Cessation; D013788:Thalamus / Q000737:chemistry / Q000503:physiopathology; D015899:Tomography, Emission-Computed, Single-Photon; D055815:Young Adult
chemical_list: D011978:Receptors, Nicotinic