Marker gene polymorphisms in hyperkinetic disorder--predictors of clinical response to treatment with methylphenidate?

Gene polymorphisms of the dopamine D4 receptor (DRD4) and serotonin transporter (5-HTT) are under discussion as potential genetic risk factors for hyperkinetic disorder (HD). In this disorder, treatment with the psychostimulant methylphenidate (MPH; Ritalin) induces calming effects and amelioration in only 70% of the patients. MPH blocks the reuptake of dopamine, thus enhancing synaptic dopamine which in turn antagonizes the release of prolactin (PL). Genotyping HD patients for DRD4 and 5-HTT polymorphisms and measuring PL concentrations, we report on an association between the combination DRD4*7/5HTT LL genotype and a reduced improvement in general functioning accompanied by different PL levels upon MPH treatment. Thus, our study supports the hypothesis that marker gene polymorphism may be helpful in identifying MPH non-responders.