Growing evidence, from animal and human studies, suggests the involvement of the dopaminergic system in alcohol- and other drug-seeking behaviors. The main purpose of this proposal is to determine whether or not genetically- and/or environmentally (stress)-induced deficits in the brain dopaminergic system predict susceptibility to these behaviors in adolescent children of alcoholic parents. A sample of 100 boys and 100 girls (13-15 year old) will be rigorously screened and selected for study. Each child will be assessed at entry for dopaminergic-related markers. These include: 1) molecular genetic (alleles (forms) of the D2 dopamine receptor and D4 dopamine receptor genes), 2) neurocognitive (P3000 amplitude and latency of the event-related potential and visuospatial abilities), 3) personality (Novelty Seeking and Extraversion) and 4) environmental (stress and response to stress) markers. The neurocognitive, personality and environmental markers will be reassessed during the 3rd year of the childrens' involvement to determine the stability of these markers. Alcohol and other drug use behaviors will be ascertained as children enter the study and also during their 3rd and 4th years of participation in the study. Finally, from this data, differential susceptibility to alcohol and other drug use behaviors will be determined from the best molecular genetic, neurocognitive, personality and stress markers, using multiple regression and confirmatory statistical modeling analyses. Previous studies from the PI's laboratory and from laboratories elsewhere provide evidence for an interrelationship among the various elements indicated above. The unique feature of this proposal is that it presents a model system which integrates genetic and environmental factors (through the common-dopaminergic system) in predicting differential susceptibility to """"""""real-world"""""""" alcohol and other drug use behaviors. This model system will be tested in a prospective longitudinal design on children of alcoholics. It is now well-acknowledged that alcohol and other drug use behaviors are a major health an social problem among adolescents in this Nation. In deed, recent surveys indicate a worsening of the problem. It is hoped that by understanding the underlying factors contributing to this problem, a more rational basis emerges for identifying high risk individuals and improving the efficacy of focused prevention efforts.
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| Conner, Bradley T; Noble, Ernest P; Berman, Steven M et al. (2005) DRD2 genotypes and substance use in adolescent children of alcoholics. Drug Alcohol Depend 79:379-87 |
| Berman, Steven M; Ozkaragoz, Tulin; Noble, Ernest P et al. (2003) Differential associations of sex and D2 dopamine receptor (DRD2) genotype with negative affect and other substance abuse risk markers in children of alcoholics. Alcohol 30:201-10 |
| Ozkaragoz, T; Noble, E P (2000) Extraversion. Interaction between D2 dopamine receptor polymorphisms and parental alcoholism. Alcohol 22:139-46 |
| Pelham, W E; Gnagy, E M; Chronis, A M et al. (1999) A comparison of morning-only and morning/late afternoon Adderall to morning-only, twice-daily, and three times-daily methylphenidate in children with attention-deficit/hyperactivity disorder. Pediatrics 104:1300-11 |
