In Vivo Evidence for β2 Nicotinic Acetylcholine Receptor Subunit Upregulation in Smokers as Compared With Nonsmokers With Schizophrenia

Biol Psychiatry. 2014 Sep 15;76(6):495-502. doi: 10.1016/j.biopsych.2013.11.001. Epub 2013 Nov 13.


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.

Keywords: Executive control; SPECT; negative symptoms; nicotinic acetylcholine receptors; psychosis; tobacco smoking.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Executive Function / physiology
  • Female
  • Humans
  • Iodine Radioisotopes
  • Male
  • Middle Aged
  • Protein Subunits
  • Receptors, Nicotinic / metabolism*
  • Schizophrenia / diagnostic imaging
  • Schizophrenia / metabolism*
  • Schizophrenic Psychology
  • Smoking / metabolism*
  • Tomography, Emission-Computed, Single-Photon
  • Up-Regulation


  • Iodine Radioisotopes
  • Protein Subunits
  • Receptors, Nicotinic
  • nicotinic receptor beta2