Genes, abuse trajectories, and prevention. The multistep nature of tobacco use progression��from initiation, to choose size episodic use, to dependence��provides several opportunities for risk factors to act. The TTURC��s research indicates that the efficacy of an intervention program depends on dispositional attributes such as hostility and depression. Within their social networks, adolescents make behavioral choices about tobacco use��choices that depend on individuals�� dispositional attributes as influenced by biological, cognitive, and emotional changes. Thus, genetic and environmental exposures that influence brain biology are potential risk factors that affect tobacco use and the efficacy of intervention programs.

To this end, researchers genotyped four variable number of tandem repeat polymorphisms (SLC6A4, SLC6A3, DRD4, and the MAO A promoter), as well as 1,295 single nucleotide polymorphisms (SNPs) in 58 genes within the neuronal nicotinic receptor and dopamine systems among the Wuhan (China) Prevention Trial cohort. Results were equivocal when examining main effects of each polymorphism. This finding was somewhat expected given the complex nature of smoking initiation. However, since previous association and functional data pointed to a major role for the MAO A promoter polymorphism, examination of effect modification for this functional polymorphism by all genotyped SNPs showed substantial effects. The most significant result was for a modification effect of MAO A by an SNP within the DRD1IP gene. This effect is seen in both males and females.

In females, the p value after adjustment for multiple correlated tests was .0001 for the interaction effect. Specifically, within females carrying the minor allele (AA or AG) for DRD1IP, the four repeat polymorphisms increased risk for initiating smoking substantially (OR = 8.7). In males carrying the DRD1IP minor allele, the effect of MAO A was 3.3. However, for both females and males, there was no observed effect for MAO A in individuals with the wild-type genotype (GG; D. Li, J. Liu, W. Lee, X. Jiang, D. Van Den Berg, A. Bergen, S. London, P. Gallaher, C.-P. Chou, J. Shih, J. Unger, C. A. Johnson, & D. V. Conti, in preparation). Ongoing analysis is examining smoking progression, interactions with prevention, and alcohol abuse. Emotional decision capacity and tobacco�Calcohol abuse trajectories.

The research indicates Batimastat that individual capacity for decisions under emotional arousal profoundly influences tobacco and alcohol abuse trajectories. Using a widely accepted behavioral assessment of emotional decision capacity developed by the Iowa Gambling Task, TTURC researchers found that adolescents who binge drink showed greater emotional decision dysfunction than did those who do not (Johnson et al., 2008).