Imaging genetics in ADHD

Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent neuropsychiatric disorder, with 5% of school age children affected. Up to 80% of the phenotypic variance can be explained by genetic factors. The intermediate or endophenotype approach allows for mapping of the effect of individual risk genes on neurobiological parameters, such as brain structure, chemistry and, ultimately, function. There are two obvious advantages of applying such an approach to complex disorders: first, these measures are causally closer to genes and gene expression than behavior, meaning that gene effects should be magnified. Second, neuroimaging provides a means to uncover the neurobiological mechanisms by which gene variants impact the brain. To date, only fourteen studies have applied an imaging genetics approach to ADHD. Eight of these used MRI, four SPECT and two EEG. These imaging modalities have afforded us a window on the brain, permitting a glimpse of how genetic changes can affect brain structure, chemistry and function. The studies to date have often focused on two prime candidate genes in the dopamine system, the DRD4 and DAT1 genes. However, the effects of neither are yet fully understood. Imaging genetics in ADHD is in its infancy. While attempts to integrate the findings to date are hinting at how genes may impact various aspects of neural functioning, studies testing clear model-based hypotheses, using multimodal approaches may provide a means to link various windows on the brain.