Plenary lecture by Jan Buitelaar, ESCAP 2009 Budapest


ESCAP 2009 Congress in Budapest, Hungary: abstract by professor Jan K. Buitelaar (Netherlands), UMC St. Radboud, Department of Psychiatry, Nijmegen –“Gene-environment interactions in ADHD”. Chaired by A. Warnke (Germany). Plenary Session I., 23 August 2009, 08:00 at the Budapest Congress & World Trade Center.

Jan BuitelaarTwin and adoption studies have indicated that ADHD has a strong genetic loading with estimated heritabilities around 80. Though the involvement of a number of candidate genes as DRD4, DRD5, DAT1, DBH, 5-HTT, HTR1B, SNAP25 had been replicated in meta-analyses based on the results of conventional family-based and case-control designs, none of these was replicated at the level of genome-wide significance (p<05x10-8) in recent GWAS studies. These GWAS studies did not reveal either other signals at the level of genome-wide significance. This supports the common variant common disease model of ADHD that describes polygenic influences (i.e. multiple interacting genes, each of small effect size with odds ratios 1.01-1.5) together with gene/environmental interactions (GxE) being responsible for individual phenotypes. The overall effect size of GxE is difficult to estimate since this is included in the compartment of additive genetic effects in twin models of heritability. The lack of genes with major pathogenic effects suggests however that gene-specific vulnerabilities may be balanced by adaptive advantages in certain circumstances, and implies aetiological heterogeneity. The aim of this presentation is to review the various theoretical models of GxE, include epigenetic effects of the environment of the expression and regulation of genes, variations in heritability according to the environment, and GxE sensu strictu. Next, to discuss findings from a series of recent studies on GxE in ADHD. Current findings include interaction effects of DAT with the early prenatal environment (exposure to alcohol and smoking) and psychosocial environment, DRD4 and the sensitivity to parenting behavior, and 5-HTT to environmental adversity and socio-economic status. We will also pay attention to GxE in explaining the comorbidity with conduct disorder in ADHD, such as the interaction between parental expressed emotion, and variation of DAT and 5-HTT. Further elaboration of GxE models of ADHD may lead to resolving the aetiological heterogeneity of ADHD, and on the basis thereof, may lead to implications for treatment.

Go to the Budapest 2009 Congress page.