The long term goal of this application is to identify the heritable components of attention deficit/hyperactivity disorder (ADHD) and related disorders and to link these heritable components to abnormalities of brain structure and function. To accomplish this long term goal we propose to establish a network of investigators on three continents who are involved in large scale twin and family studies which include the assessment of ADHD. The proposed network of investigators has been involved in studies resulting in a series of different conceptualizations of ADHD ranging from clinic based categorical models as found in DSM-IV to population based continuum and cluster models. The first goal of this network is to combine data sets and analytic expertise to try to better define what the heritable components of ADHD are and to contrast different methodological conceptualizations of ADHD by their ability to explain family transmission. In order to link these phenotypic and genetic analyses to the larger literature of abnormalities of brain structure and function in ADHD we will complete a pilot study of structural brain imaging on a subgroup of sibling pairs which have been selected to be extremely discordant with respect to ADHD symptoms. Specifically, results of different analytic strategies will be compared across four data sets (twins from Missouri, Australia and the Netherlands and nontwin families from Vermont) including quantitative, latent class and comorbidity approaches. Each approach taps a different theoretical concept about the structure of ADHD and what is heritable. The ability of each phenotypic model to predict biological deficits will be compared by measuring the correspondence of each approach to brain imaging deficits in a subsample of sibling pairs. This pilot MRI study requires large sample sizes to identify rare, extremely discordant sibling pairs. All four Centers will contribute analytic expertise to the analysis of all the data sets and each Center will collect MRI information on a limited number of rare sibling pairs. The success of this application will result in an expanded set of studies which are cross-cultural and epidemiologic in nature, and which will provide new conceptualizations for the study of ADHD in terms of heritability, clinical symptomatology, brain structure and function, and clinical response to treatment.
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| van 't Ent, D; Lehn, H; Derks, E M et al. (2007) A structural MRI study in monozygotic twins concordant or discordant for attention/hyperactivity problems: evidence for genetic and environmental heterogeneity in the developing brain. Neuroimage 35:1004-20 |
| Todd, Richard D; Huang, Hongyan; Smalley, Susan L et al. (2005) Collaborative analysis of DRD4 and DAT genotypes in population-defined ADHD subtypes. J Child Psychol Psychiatry 46:1067-73 |
