""""""""Behavioral Genetics of Mood-Induced Smoking"""""""" Controlled laboratory studies reliably show that negative mood manipulations of various kinds acutely increase smoking reinforcement. However, very few studies have identified individual differences that moderate mood-induced smoking, and only one, a recent report by us, has examined genetic associations. The primary aim of this proposal is to validate our prior, preliminary data on genetic associations with increases in smoking due to negative mood, a potentially important novel phenotype for nicotine dependence. Dependent smokers (N=200) will participate in two virtually identical lab sessions, differing only in induction of negative vs. positive mood via a validated procedure to robustly induce mood (one mood per session, sessions in counter-balanced order). They will ad lib smoke their preferred brand of cigarettes (to maximize generalizability) during mood induction each session. Differences in smoking reinforcement (latency and amount of smoking) between the negative and positive mood conditions, i.e. mood-induced smoking, will be related to the dopamine and mu opioid receptor gene variants identified in our preliminary study. These include: dopamine D4 receptor (DRD4 VNTR), dopamine D2 receptor (DRD2 C957T SNP [rs6277] and DRD2/ANKK1 TaqIA SNP [rs1800497]), the dopamine transporter (SLC6A3 VNTR), and the mu opioid receptor exon 1 SNP (OPRM1 A118G [rs1799971]). In secondary aims, we will examine genetic associations with smoking reward, affect, and related measures, as well as other individual differences in mood-induced smoking, including subject sex, depression history, distress tolerance, and severity of nicotine dependence. Our prior study and past productive collaborations between the PI and co-I demonstrate the strong feasibility of this proposal. Results of this innovative project may identify smokers potentially at greater risk for relapse due to negative mood and may guide research on mechanisms behind mood-induced smoking. Our procedures could be used to test the efficacy of medications to attenuate mood-induced smoking, thereby reducing vulnerability of some smokers to mood-related relapse. This project also could be a prototype for future research that combines rigorous behavioral pharmacology methodology and genetics to identify individual variation in drug reinforcement due to situational influences.

Public Health Relevance

Negative mood increases smoking behavior and leads to relapse after a quit attempt. Controlled laboratory studies show that negative mood manipulations of various kinds (e.g. stressors) acutely increase smoking behavior. However, very few studies have identified individual differences in mood-induced smoking, and only one, a preliminary study by us, examined genetic associations with mood-induced smoking. This project will validate our preliminary observations, which may identify smokers particularly vulnerable (or resistant) to smoking relapse due to negative mood. Results may guide research on genetics of environmental influences on smoking behavior and other drug abuse, and perhaps guide research on the mechanisms behind mood-induced smoking.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Small Research Grants (R03)
Project #
1R03DA027449-01
Application #
7761384
Study Section
Special Emphasis Panel (ZDA1-SXC-E (03))
Program Officer
Gordon, Harold
Project Start
2009-09-15
Project End
2011-08-31
Budget Start
2009-09-15
Budget End
2010-08-31
Support Year
1
Fiscal Year
2009
Total Cost
$233,255
Indirect Cost
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Perkins, Kenneth A; Karelitz, Joshua L; Giedgowd, Grace E et al. (2013) Negative mood effects on craving to smoke in women versus men. Addict Behav 38:1527-31
Perkins, Kenneth A; Karelitz, Joshua L; Giedgowd, Grace E et al. (2012) The reliability of puff topography and subjective responses during ad lib smoking of a single cigarette. Nicotine Tob Res 14:490-4
Perkins, Kenneth A; Giedgowd, Grace E; Karelitz, Joshua L et al. (2012) Smoking in response to negative mood in men versus women as a function of distress tolerance. Nicotine Tob Res 14:1418-25
Perkins, Kenneth A; Giedgowd, Grace E; Karelitz, Joshua L et al. (2012) Expectancy for negative affect relief due to smoking may not be predictive under acute mood situations. Exp Clin Psychopharmacol 20:161-6
Perkins, Kenneth A; Karelitz, Joshua L; Conklin, Cynthia A et al. (2010) Acute negative affect relief from smoking depends on the affect situation and measure but not on nicotine. Biol Psychiatry 67:707-14
Perkins, Kenneth A; Karelitz, Joshua L; Giedgowd, Grace E et al. (2010) Differences in negative mood-induced smoking reinforcement due to distress tolerance, anxiety sensitivity, and depression history. Psychopharmacology (Berl) 210:25-34
Perkins, Kenneth A (2009) Discriminative stimulus effects of nicotine in humans. Handb Exp Pharmacol :369-400