Recent advances in smoking cessation have focused on the use of antidepressants for the treatment of nicotine dependence (i.e., bupropion and nortriptyline). While the efficacy of these treatments has been established in previous studies, we know little about how they work, particularly on symptoms of negative affect, which are both a strong predictor of relapse and a primary target of these drugs. The impact of these and other pharmacological treatments may be enhanced by improving our understanding of the psychobiological and genetic mechanisms associated with the modulation of mood during cessation and the interaction between these mechanisms and treatment.
The specific aims of this project are to assess the effects of these drugs on changes in emotional reactivity during cessation, and to determine if these effects are moderated by genotype. We will also determine whether emotional reactivity predicts time to relapse. The startle reflex (eye blink) is an emerging technology for studying the impact of drugs, genetic factors and other psychobiological mechanisms on emotional processing. The startle reflex is an orienting response that follows an unexpected auditory stimulus (startle probe). Negative emotional cues (unpleasant pictures) activate defensive neuroregulatory pathways and increase blink response magnitude (eye muscle EMG), while positive cues (pleasant pictures) inhibit the response, activating appetitive or approach behavior, in defensive activation, while positive cues inhibit the response (appetitive activation). Our previous studies suggest that this response is modulated before and after quitting by the DRD2 genotype. In this study, up to 354 smokers will be randomly assigned to receive bupropion, nortriptyline or placebo. Participants will complete a startle assessment at baseline (pre-quit) and at 2, 5 and 28 days post-quit, consisting of the presentation of an acoustic stimulus (startle probe), immediately preceded by positive, negative or neutral emotional cues or smoking related stimuli. We hypothesize that the emotional reactivity of all smokers during cessation will be significantly less for those treated with either antidepressant in comparison to placebo. It is also hypothesized that emotional reactivity will be lower for those carrying the DRD2 A1 allele and using bupropion versus A1 smokers using either nortriptyline or placebo. Homozygous A2s are expected to respond similarly to both drugs with higher levels of emotional reactivity being observed for placebo. We will also characterize other potential markers for neurotransmitter function (DRD4, DAT, SERT, NET) in terms of differences in both baseline emotional reactivity, and response to pharmacotherapy vs: the control. We hope to understand more fully how pharmacotherapies for smoking cessation affect emotional reactivity during cessation (nicotine withdrawal) and what role genetics may play in conferring an advantage to one treatment versus another, through this mechanism. Ultimately this knowledge may be applied to the development of more effective smoking cessation treatments, especially in the area of pharmacogenetics.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA017073-03
Application #
7050178
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Gordon, Harold
Project Start
2004-07-15
Project End
2009-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
3
Fiscal Year
2006
Total Cost
$531,714
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Type
Schools of Medicine
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030
Zhu, Hongxiao; Versace, Francesco; Cinciripini, Paul M et al. (2018) Robust and Gaussian spatial functional regression models for analysis of event-related potentials. Neuroimage 181:501-512
Cui, Yong; Engelmann, Jeffrey M; Xian, Jonathan et al. (2018) Pharmacological intervention and abstinence in smokers undergoing cessation treatment: A psychophysiological study. Int J Psychophysiol 123:25-34
Zhu, Hongxiao; Caspers, Philip; Morris, Jeffrey S et al. (2018) A Unified Analysis of Structured Sonar-terrain Data using Bayesian Functional Mixed Models. Technometrics 60:112-123
Zhu, Hongxiao; Morris, Jeffrey S; Wei, Fengrong et al. (2017) Multivariate functional response regression, with application to fluorescence spectroscopy in a cervical pre-cancer study. Comput Stat Data Anal 111:88-101
Cinciripini, Paul M; Green, Charles E; Robinson, Jason D et al. (2017) Benefits of varenicline vs. bupropion for smoking cessation: a Bayesian analysis of the interaction of reward sensitivity and treatment. Psychopharmacology (Berl) 234:1769-1779
Cui, Yong; Robinson, Jason D; Engelmann, Jeffrey M et al. (2015) Reinforcement sensitivity underlying treatment-seeking smokers' affect, smoking reinforcement motives, and affective responses. Psychol Addict Behav 29:300-311
Versace, Francesco; Engelmann, Jeffrey M; Robinson, Jason D et al. (2014) Prequit fMRI responses to pleasant cues and cigarette-related cues predict smoking cessation outcome. Nicotine Tob Res 16:697-708
Minnix, Jennifer A; Versace, Francesco; Robinson, Jason D et al. (2013) The late positive potential (LPP) in response to varying types of emotional and cigarette stimuli in smokers: a content comparison. Int J Psychophysiol 89:18-25
Cui, Yong; Versace, Francesco; Engelmann, Jeffrey M et al. (2013) Alpha oscillations in response to affective and cigarette-related stimuli in smokers. Nicotine Tob Res 15:917-24
Cinciripini, Paul M; Robinson, Jason D; Karam-Hage, Maher et al. (2013) Effects of varenicline and bupropion sustained-release use plus intensive smoking cessation counseling on prolonged abstinence from smoking and on depression, negative affect, and other symptoms of nicotine withdrawal. JAMA Psychiatry 70:522-33

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