|Grant Number:||5P50CA084719-04 Interpret this number|
|Primary Investigator:||Abrams, David|
|Project Title:||Nicotine Dependence: Risk & Recovery Over Generations|
DESCRIPTION: (Applicant's Description) The overall aim of this TTURC is to identify familial, early childhood and lifetime psychiatric factors that determine: trajectories of progression from smoking initiation to dependence; lifetime smoking patterns; the natural course of cessation; and response to treatment. Our proposed program of research combines a treatment/prevention imperative, a genetic epidemiologic approach, and a lifespan developmental perspective, sharing common scientific resources, to advance research on human nicotine dependence from basic mechanisms to applied interventions. We will use a synergistic combination of a community-based sample, prospective design, and a multigenerational family study to examine the major pathways to nicotine dependence, and to develop and validate a lifespan taxonomy of tobacco use and nicotine dependence phenotypes. The major goal is to identify modifiable risk factors that can serve as targets for prevention and that may be harnessed to enhance smoking prevention and cessation treatment success. We recognize that many such modifiable risk factors may act in concert with or against a substrate of genetic risks, and reason that a combined environmental and genetic/familial strategy is required both to clearly identify salient environmental agents and to prepare for studies of susceptibility genes. To this end, we propose to: l) To integrate multiple disciplinary perspectives and research methods front basic science to applications including (a) longitudinal natural history research (developmental epidemiology); (b) familial aggregation methods (genetic epidemiology); (c) human laboratory studies; and (d) intervention trials; (2) To adopt this lifespan and transgenerational genetic epidemiological approach to help understand risk factors for and causal pathways of: (a) progression of nicotine dependence among youth; (b) patterns of adult smoking; (c) the natural course of smoking cessation; and (d) response to treatment; (3) To document the potential utility and cost-effectiveness of a sustained "care management" approach to treating smokers that addresses smokers' risk profiles (from relatively uncomplicated to multiple comorbidities) with a range of treatment options that vary along dimensions of intensity and modality of intervention; (4) To collect and preserve DNA with the anticipation that, after refining phenotypic definitions, characterizing candidate genes (in other samples), and identifying the most heritable forms of smoking behavior, we may inform and conduct an efficient and productive strategy to identify susceptibility genes for nicotine dependence.
Prenatal glucocorticoids and maternal smoking during pregnancy independently program adult nicotine dependence in daughters: a 40-year prospective study.
Authors: Stroud LR, Papandonatos GD, Shenassa E, Rodriguez D, Niaura R, LeWinn KZ, Lipsitt LP, Buka SL
Source: Biol Psychiatry, 2014 Jan 1;75(1), p. 47-55.
EPub date: 2013 Sep 10.
Direct and moderating links of salivary alpha-amylase and cortisol stress-reactivity to youth behavioral and emotional adjustment.
Authors: Allwood MA, Handwerger K, Kivlighan KT, Granger DA, Stroud LR
Source: Biol Psychol, 2011 Sep;88(1), p. 57-64.
EPub date: 2011 Jul 21.
Dopamine D4 receptor gene variation moderates the efficacy of bupropion for smoking cessation.
Authors: Leventhal AM, David SP, Brightman M, Strong D, McGeary JE, Brown RA, Lloyd-Richardson EE, Munaf˛ M, Uhl GR, Niaura R
Source: Pharmacogenomics J, 2012 Feb;12(1), p. 86-92.
EPub date: 2010 Jul 27.
Quitting smoking and change in alcohol consumption in the International Tobacco Control (ITC) Four Country Survey.
Authors: Kahler CW, Borland R, Hyland A, McKee SA, O'Connor RJ, Fong GT, Cummings KM
Source: Drug Alcohol Depend, 2010 Jul 1;110(1-2), p. 101-7.
EPub date: 2010 Mar 15.
Relationships of personality and psychiatric disorders to multiple domains of smoking motives and dependence in middle-aged adults.
Authors: Kahler CW, Leventhal AM, Daughters SB, Clark MA, Colby SM, Ramsey SE, Boergers J, Abrams DB, Niaura R, Buka SL
Source: Nicotine Tob Res, 2010 Apr;12(4), p. 381-9.
EPub date: 2010 Feb 18.
Sex differences in TTC12/ANKK1 haplotype associations with daily tobacco smoking in Black and White Americans.
Authors: David SP, Mezuk B, Zandi PP, Strong D, Anthony JC, Niaura R, Uhl GR, Eaton WW
Source: Nicotine Tob Res, 2010 Mar;12(3), p. 251-62.
EPub date: 2010 Feb 4.
Predictors of abstinence and changes in psychiatric symptoms in a pooled sample of smokers with schizophrenia receiving combination pharmacotherapy and behavioral therapy for smoking cessation.
Authors: Weinberger AH, Hitsman B, Papandonatos GD, Sacco KA, Vessicchio JC, George TP
Source: J Clin Psychopharmacol, 2009 Dec;29(6), p. 601-3.
Personality, psychiatric disorders, and smoking in middle-aged adults.
Authors: Kahler CW, Daughters SB, Leventhal AM, Rogers ML, Clark MA, Colby SM, Boergers J, Ramsey SE, Abrams DB, Niaura R, Buka SL
Source: Nicotine Tob Res, 2009 Jul;11(7), p. 833-41.
EPub date: 2009 May 26.
Elevated maternal cortisol levels during pregnancy are associated with reduced childhood IQ.
Authors: LeWinn KZ, Stroud LR, Molnar BE, Ware JH, Koenen KC, Buka SL
Source: Int J Epidemiol, 2009 Dec;38(6), p. 1700-10.
EPub date: 2009 May 7.
Maternal smoking during pregnancy and neonatal behavior: a large-scale community study.
Authors: Stroud LR, Paster RL, Goodwin MS, Shenassa E, Buka S, Niaura R, Rosenblith JF, Lipsitt LP
Source: Pediatrics, 2009 May;123(5), p. e842-8.
Stress response and the adolescent transition: performance versus peer rejection stressors.
Authors: Stroud LR, Foster E, Papandonatos GD, Handwerger K, Granger DA, Kivlighan KT, Niaura R
Source: Dev Psychopathol, 2009 Winter;21(1), p. 47-68.
Alcohol consumption and quitting smoking in the International Tobacco Control (ITC) Four Country Survey.
Authors: Kahler CW, Borland R, Hyland A, McKee SA, Thompson ME, Cummings KM
Source: Drug Alcohol Depend, 2009 Mar 1;100(3), p. 214-20.
EPub date: 2008 Dec 3.
Molecular genetics of addiction and related heritable phenotypes: genome-wide association approaches identify "connectivity constellation" and drug target genes with pleiotropic effects.
Authors: Uhl GR, Drgon T, Johnson C, Li CY, Contoreggi C, Hess J, Naiman D, Liu QR
Source: Ann N Y Acad Sci, 2008 Oct;1141, p. 318-81.
Linking measures of adolescent nicotine dependence to a common latent continuum.
Authors: Strong DR, Kahler CW, Colby SM, Griesler PC, Kandel D
Source: Drug Alcohol Depend, 2009 Jan 1;99(1-3), p. 296-308.
EPub date: 2008 Oct 19.
A twin study of smoking, nicotine dependence, and major depression in men.
Authors: Lyons M, Hitsman B, Xian H, Panizzon MS, Jerskey BA, Santangelo S, Grant MD, Rende R, Eisen S, Eaves L, Tsuang MT
Source: Nicotine Tob Res, 2008 Jan;10(1), p. 97-108.
Pharmacogenetic clinical trial of sustained-release bupropion for smoking cessation.
Authors: David SP, Brown RA, Papandonatos GD, Kahler CW, Lloyd-Richardson EE, Munaf˛ MR, Shields PG, Lerman C, Strong D, McCaffery J, Niaura R
Source: Nicotine Tob Res, 2007 Aug;9(8), p. 821-33.
Long-term stability of maternal prenatal steroid hormones from the National Collaborative Perinatal Project: still valid after all these years.
Authors: Stroud LR, Solomon C, Shenassa E, Papandonatos G, Niaura R, Lipsitt LP, Lewinn K, Buka SL
Source: Psychoneuroendocrinology, 2007 Feb;32(2), p. 140-50.
EPub date: 2007 Jan 31.