Date of Award
Bruce F. Pennington, Ph.D.
ADHD, Environment, Gene, Interaction, Molecular
The overall goal of this project is to advance our understanding of the multifactorial etiology of Attention Deficit Hyperactivity Disorder (ADHD) by testing a diathesis-stress model of gene x environment (g x e) interactions. Although the literature increasingly supports g x e interactions in the manifestation of ADHD, few studies have investigated multiple genetic and environmental risk factors, included direct tests of gene - environment correlations (rG-Es), explored the specificity of interactions to symptom dimensions, or attempted to minimize comparisons. Therefore, utilizing both within-family (FBAT/PBAT) and case-control methodology, this study sought to (1) explore main effects of polymorphisms in the DRD2, DRD4, DRD5, DAT1, 5HTT, ADRA2C and DBH genes on ADHD symptoms in a community sample, (2) explore main effects of environmental risk factors on ADHD symptoms (including direct tests of gene - environment correlation), (3) test for g x e interaction effects between those environmental and genetic risk factors substantiated by main effects, and (4) investigate whether results were specific to particular symptom dimensions of ADHD. Analyses demonstrated a robust main effect of the DRD4 4-repeat allele (DRD4*4R) on ADHD symptoms rather than the DRD4 7-repeat allele (DRD4*7R), that had previously been implicated in ADHD. Analyses also revealed main effects of maternal smoking, prenatal alcohol exposure, season of birth, parental education, and television viewing habits on ADHD symptoms. After considering rG-Es, results demonstrated significant diathesis-stress g x e interactions between DRD4*4R and season of birth, maternal smoking, and parental education that selectively exacerbated hyperactive-impulsive (HI) symptoms. Exploratory analyses demonstrated a main effect of the DAT1 10-repeat allele (DAT1*10R) on ADHD-Combined Type and HI symptoms, and revealed significant interactions between DAT1*10R and parental education and season of birth on HI behaviors. Taken together, these data are consistent with a diathesis-stress model for g x e interactions in ADHD, suggest a possible alternate risk factor in linkage disequilibrium with DRD4*4R and DRD4*7R that may be the true "risk" allele, provide evidence that DAT1*10R may play into a subtype-specific etiology for ADHD-C, and support the idea that polymorphisms in dopaminergic genes interact with parental education and season of birth to selectively exacerbate HI symptoms.
Barnard, Holly Donovan, "Gene-Environment Interactions in Attention Deficit Hyperactivity Disorder" (2009). Electronic Theses and Dissertations. 54.
Received from ProQuest
Holly Donovan Barnard