| Much research has focused on the Attention Deficit Hyperactivity Disorder (ADHD). Results indicated that the disorder is highly influences by heritable factors (almost 80%). However, the exact genetic underpinnings have yet to be revealed. Molecular genetic research has been hampered by the heterogeneity of the disorder: many children with ADHD portray problems in inhibition, although not every child with ADHD does. This heterogeneity may indicate that (homogeneous) subtypes within the disorder may have (in part) a different genetic basis. Endophenotypes may come into play here and form useful tools for discovering risk genes. Endophenotypes form a link between the genetic make-up (genotype) of an individual and the observable behaviour (phenotype). Endophenotypes are theorized as forming underlying vulnerability traits that heighten the risk for developing the disorder. The aim of my PhD-thesis is to explore candidate neuropsychological endophenotypes of ADHD. I?m also interested to what extent endophenotypes translate to ADHD symptoms and if certain factors may come into play here. It will also be explored if candidate ADHD-endophenotypes also relate to comorbid disorders (such as behavioural problems, reading problems, motor coordination problems, anxious behaviour, and autistic traits) in order to gain insight into the unique and shared pathways leading up to disorders in childhood. Finally, a genetic basis for these endophenotypes will be explores through linkage and (whole genome) association. A characteristic of an endophenotype is that non-affected siblings of patients with ADHD also suffer from deficits in that endophenotype. This may relate to non-affected siblings carrying (some) susceptibility genes for ADHD, since non-affected siblings share about 50% of their genes with their affected siblings. Therefore, we investigated not only the neuropsychological functioning of children with ADHD, but also the neuropsychological functioning of their siblings. In cooperation with the International Multi-center ADHD Genes study (IMAGE) and the Radboud University Nijmegen, a total of 238 families participated in which at least one child suffered from ADHD. An additional 271 control families participated. The neuropsychological test battery consisted out of executive tasks (inhibition, visuo-spatial and verbal working memory), sense of timing, and motor functioning (control and timing of motor output). Results are presented in the list of publications. |
