During this year, we reported genome wide association for smoking cessation success in data from an additional clinical trial, with AUROC for a predictive smoking quit success score of 0.64. Smoking quit success genes identified in this fashion include genes that we have identified in studies of addiction vulnerability. A sizable number of these genes have products that are involved in cell adhesion molecule actions. Several are likely to be involved in learning and memory mechanisms. Several are implicated in indivdual differences in regional brain volumes. During this year, we published a novel synthesis of animal models for smoking cessatin focused on mouse models. We have applied many of these tests to an animal model for one of the genes implicated from human studies, CDH13. Extinction/reinstatement of cocaine conditioned place preferences display trends toward difference in CDH13 KO mice;we are currently working with nicotine CPP in these animals. During this year, we reported work that links, for the first time, individual differences in abilities to quit smoking with individual differences in uptake of use of addictive substances, including cigarettes. During this year, we have also followed up on data that identified nominally-significant associations between TRPA1 haplotypes and success in smoking cessation in European Americans. The modest numbers of African American individuals who prefer non mentholated cigarettes disproportionately display TRPA1 alleles that are likely to derive from individuals with European ancestries, at least in 5'aspects of the gene. Chromosomes with apparent recombination at this locus are also identified among African-American smokers who prefer nonmentholated cigarettes.

Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2013
Total Cost
$88,025
Indirect Cost
Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
Zip Code
Musci, Rashelle J; Masyn, Katherine E; Benke, Kelly et al. (2016) The effects of the interplay of genetics and early environmental risk on the course of internalizing symptoms from late childhood through adolescence. Dev Psychopathol 28:225-37
Stein, Renee; Shapatava, Ekaterine; Williams, Weston et al. (2015) Reduced Sexual Risk Behaviors Among Young Men of Color Who Have Sex with Men: Findings from the Community-Based Organization Behavioral Outcomes of Many Men, Many Voices (CBOP-3MV) Project. Prev Sci 16:1147-58
Musci, Rashelle J; Uhl, George; Maher, Brion et al. (2015) Testing gene × environment moderation of tobacco and marijuana use trajectories in adolescence and young adulthood. J Consult Clin Psychol 83:866-74
Musci, Rashelle J; Bradshaw, Catherine P; Maher, Brion et al. (2014) Erratum to: Reducing Aggression and Impulsivity Through School-Based Prevention Programs: A Gene by Intervention Interaction. Prev Sci :
Ishiguro, Hiroki; Hall, Frank S; Horiuchi, Yasue et al. (2014) NrCAM-regulating neural systems and addiction-related behaviors. Addict Biol 19:343-53
Uhl, George R; Drgonova, Jana (2014) Cell adhesion molecules: druggable targets for modulating the connectome and brain disorders? Neuropsychopharmacology 39:235
Uhl, George R; Drgonova, Jana; Hall, F Scott (2014) Curious cases: Altered dose-response relationships in addiction genetics. Pharmacol Ther 141:335-46
Musci, Rashelle J; Bradshaw, Catherine P; Maher, Brion et al. (2014) Reducing aggression and impulsivity through school-based prevention programs: a gene by intervention interaction. Prev Sci 15:831-40
Uhl, G R; Walther, D; Musci, R et al. (2014) Smoking quit success genotype score predicts quit success and distinct patterns of developmental involvement with common addictive substances. Mol Psychiatry 19:50-4
Bough, K J; Lerman, C; Rose, J E et al. (2013) Biomarkers for smoking cessation. Clin Pharmacol Ther 93:526-38

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