Deficits in response inhibition are considered as candidate endophenotypes of altered prefrontal brain function in Attention Deficit Hyperactivity Disorder (ADHD). Electrophysiological methods like Event-Related Potentials (ERPs) are adequate to measure abnormalities in brain functions underlying those deficits and to assess functionally relevant polymorphisms directly affecting neurotransmission systems and brain function. This principle of imaging genomics with ERPs has been demonstrated as early as 1999 for the serotonin transporter promoter polymorphism affecting prefrontal brain function (Fallgatter et al., International Journal of Neuropsychopharmacology, 1999).

We employed a multi-channel EEG during performance of a Go-NoGo task to assess the electrophysiological basis of response inhibition. The ERP-measure derived from this protocol was termed NoGo-Anteriorisation (NGA) and is characterized by a high interindividual stability, high short- and long-term test-retest reliability and, moreover, is independent from age- and gender.

In patients with ADHD during childhood and adulthood the NGA was diminished as compared to age- and sexmatched healthy controls. Furthermore, a three-dimensional source location analysis with LORETA indicated an electrical dysfunction of the ACC in the patient groups. Moreover, the 158 val/val variants of the COMT gene were associated with an even worse prefrontal brain function.

These results exemplify the measurement of disease related disturbances in brain function in ADHD with ERPs. Future studies will show whether such electrophysiological endophenotypes may contribute to the diagnosis of subgroups of ADHD and whether they may serve as endophenotypes to further clarify genetic contributions to the disease.