Building Research into the Mission at UNLV

University Of Nevada Las Vegas, Las Vegas NV

Investigators

Abstract

Attention-Deficit/Hyperactivity Disorder (AD/HD) is a complex genetic disorder whose clinical presentation varies along several dimensions. First, within the AD/HD diagnosis, children are subtyped according to the relative distribution of its primary features, resulting in one of three major classifications (i.e., Combined, Predominantly Inattentive, and Predominantly Hyperactive-Impulsive subtypes). Second, children with AD/HD can display further variability in terms of the presence or absence of comorbid conditions, encompassing various externalizing and internalizing conditions. Finally, the clinical presentation of AD/HD often changes over time. Candidate gene studies and genomic screen analyses have thus far failed to identify the specific genetic factors influencing AD/HD. Results across studies have been conflicting and difficult to interpret. However, none of these studies has evaluated the genetic influences on AD/HD etiology while considering potential developmental changes in subtyping and comorbidity. To the extent that developmental changes in AD/HD subtyping or comorbidity occur, clinical assessments at a single point in time are less likely to capture a child's "true" diagnostic status. Thus, we assert that phenotypic assessment of AD/HD that considers its heterogeneity with respect to subtype and comorbidity across development will be a powerful tool in the successful delineation of genetic risk factors in this disorder. Specifically, we will ascertain 200 AD/HD families of which 100 families will have 2 or more AD/HD affected siblings. Children will be clinically assessed at two time points through state-of-the art psychological assessment procedures to capture DSM-IV subtyping categories and comorbid conditions. These data will be used in both candidate gene association analysis and a genomic screen in order to identify molecular genetic differences related to the temporal persistence of AD/HD.