☆ 4.7 Article

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

BIOLOGICAL PSYCHIATRY (2014)

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Journal

BIOLOGICAL PSYCHIATRY
Volume 76, Issue 6, Pages 495-502

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2013.11.001

Keywords

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

Categories

Neurosciences Psychiatry

Funding

  1. National Alliance for Research on Schizophrenia and Depression
  2. Department of Veterans Affairs
  3. Astra Zeneca
  4. Abbott Laboratories
  5. Forest Laboratories
  6. Organon
  7. Pfizer, Inc.
  8. Targacept
  9. Eli Lilly, Inc.
  10. [MH077681]
  11. [DA14241]
  12. [K01MH092681]
  13. [K02DA031750]
  14. [R01 DA - 022495]
  15. [R01DA015577]

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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 beta(2)-subunit-containing nicotinic acetylcholine receptors (beta(2)*-nAChRs). Methods: Smoking and nonsmoking subjects with schizophrenia (n = 31) and age-, smoking-, and sex-matched comparison subjects (n = 31) participated in one [I-123]5-IA-85380 single photon emission computed tomography scan to quantify beta(2)*-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 beta(2)*-nAChR availability relative to comparison group, and nonsmokers had lower beta(2)*-nAChR availability relative to smokers. However, there was no smoking by diagnosis interaction. Relative to nonsmokers with schizophrenia, smokers with schizophrenia had higher beta(2)*-nAChR availability in limited brain regions. In smokers with schizophrenia, higher beta(2)*-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 beta(2)*-nAChR availability in schizophrenia. Conclusions: Although subjects with schizophrenia have lower beta(2)*-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.

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