A greater understanding of phenotypic characteristics of, and of genetic influences on, nicotine withdrawal may help decrease morbidity and mortality in heavily dependent and relapsing smokers. The Candidate is applying for a Mentored Clinical Scientist Development Award (K08) in order to develop an independent line of research to address this serious problem. The PI has extensive experience in smoking cessation research and seeks to augment her training in statistical genetics and related quantitative methods, and assessment of tobacco use behaviors, and to increase her familiarity with molecular genetics procedures, and the neurobiology of nicotine. The goal of this research is to develop an improved assessment of nicotine withdrawal for genetic research, guided by findings from animal and previous human research, using interview and laboratory measures of negative affect, positive affect, and physical symptoms of withdrawal; and to apply this in a case-control study of genetic association. The first stage will be analysis of existing data, to determine the genetic structure of DSM-IV nicotine withdrawal symptoms, and the degree of overlap of genetic influences on nicotine withdrawal versus regular smoking, after control for other psychiatric and sociodemographic risk factors. Concurrently a small laboratory study (N=60) will address the validity and short-term reliability of factors derived from a more extensive battery of withdrawal symptoms. Guided by these results, an extensive follow-up assessment of nicotine withdrawal will be conducted in Australia of a target sample of 400 cases reporting withdrawal, and 400 controls (selection guided by first stage analyses), from whom DMAs and baseline DSM-IV interview data have already been obtained. The baseline assessment of nicotine withdrawal will be augmented by adding reliable and valid questions about decreases in positive as well as negative affect and physical symptoms. Three candidate genes (CHRNB2, OPRM1, CHRNA3) will be typed and tested for hypothesized differential associations with negative affect versus positive affect versus physical symptoms. The long-term goal of this research and training program is to prepare the applicant to establish an independent research career combining retrospective and contemporaneous assessments, both laboratory-based and interview, in pharmacogenetic research on smoking cessation failure and nicotine withdrawal.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DA019951-03
Application #
7271285
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Wanke, Kay
Project Start
2005-08-01
Project End
2010-07-31
Budget Start
2007-08-01
Budget End
2008-07-31
Support Year
3
Fiscal Year
2007
Total Cost
$124,710
Indirect Cost
Name
Washington University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Whitfield, John B; Heath, Andrew C; Madden, Pamela A F et al. (2018) Effects of high alcohol intake, alcohol-related symptoms and smoking on mortality. Addiction 113:158-166
Pardiñas, Antonio F; Holmans, Peter; Pocklington, Andrew J et al. (2018) Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection. Nat Genet 50:381-389
Agrawal, A; Chou, Y-L; Carey, C E et al. (2018) Genome-wide association study identifies a novel locus for cannabis dependence. Mol Psychiatry 23:1293-1302
Bigdeli, T B; Ripke, S; Peterson, R E et al. (2017) Genetic effects influencing risk for major depressive disorder in China and Europe. Transl Psychiatry 7:e1074
Maciejewski, Dominique F; Renteria, Miguel E; Abdellaoui, Abdel et al. (2017) The Association of Genetic Predisposition to Depressive Symptoms with Non-suicidal and Suicidal Self-Injuries. Behav Genet 47:3-10
Power, Robert A; Tansey, Katherine E; Buttenschøn, Henriette Nørmølle et al. (2017) Genome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. Biol Psychiatry 81:325-335
Gormley, Padhraig; Anttila, Verneri; Winsvold, Bendik S et al. (2016) Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine. Nat Genet 48:856-66
Otowa, T; Hek, K; Lee, M et al. (2016) Meta-analysis of genome-wide association studies of anxiety disorders. Mol Psychiatry 21:1391-9
Yang, Yuanhao; Zhao, Huiying; Heath, Andrew C et al. (2016) Familial Aggregation of Migraine and Depression: Insights From a Large Australian Twin Sample. Twin Res Hum Genet 19:312-21
Schwantes-An, Tae-Hwi; Zhang, Juan; Chen, Li-Shiun et al. (2016) Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts. Behav Genet 46:151-69

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