title: Biomarkers of Response to Smoking Cessation Pharmacotherapies: Progress to Date.
abstract: For the past 30 years, research examining predictors of successful smoking cessation treatment response has focused primarily on clinical variables, such as levels of tobacco dependence, craving, and self-efficacy. However, recent research has begun to determine biomarkers (such as genotype, nicotine and metabolite levels, and brain imaging findings) that may have utility in predicting smoking cessation. For genotype, genes associated with nicotinic acetylcholine receptors (nAChRs) and related proteins have been found to predict response to first-line medications (e.g. nicotine replacement therapy [NRT], bupropion, or varenicline) or quitting over time without a controlled treatment trial. For nicotine and metabolite levels, function of the cytochrome P450 2A6 liver enzyme, which can be assessed with the nicotine metabolite ratio or via genotype, has been found to predict response, with slow nicotine metabolizers having less severe nicotine dependence and a greater likelihood of quitting with NRT than normal metabolizers. For brain imaging, decreased activation of brain regions associated with emotion regulation and increased connectivity in emotion regulation networks, increased responsiveness to pleasant cues, and altered activation with the Stroop effect have been found in smokers who quit with the first-line medications listed above or counseling. In addition, our group recently demonstrated that lower pre-treatment brain nAChR density is associated with a greater chance of quitting smoking with NRT or placebo. Several of these studies found that specific biomarkers may provide additional information for predicting response beyond subjective symptom or rating scale measures, thereby giving an initial indication that biomarkers may, in the future, be useful for guiding smoking cessation treatment intensity, duration, and type.
authors.affiliation: Departments of Research and Psychiatry, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Mamoun
authors.affiliation: Center for Health Sciences, SRI International, Menlo Park, CA, USA.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Bergen
authors.affiliation: Department of Neurology, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Shieh
authors.affiliation: Department of Psychiatry, University of Southern California, Los Angeles, CA, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Wiggins
authors.affiliation: Departments of Research and Psychiatry, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA. abrody@ucla.edu.|Department of Psychiatry, University of California at Los Angeles, 300 UCLA Medical Plaza, Suite 2200, Los Angeles, CA, 90095, USA. abrody@ucla.edu.
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Brody
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000503:physiopathology; D006801:Humans; D012907:Smoking / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology*; D016540:Smoking Cessation / Q000379:methods; D061485:Tobacco Use Cessation Devices
chemical_list: D015415:Biomarkers