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.
Seeger
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Department of Child and Adolescent Psychiatry, Central Institute of Mental Health Mannheim, D-68072 Mannheim, Germany. Seeger@as200.zi-mannheim.de
Schloss
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Schmidt
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D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D002648:Child; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics; D026901:Membrane Transport Proteins; D008774:Methylphenidate / Q000627:therapeutic use*; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011388:Prolactin / Q000097:blood; D017448:Receptors, Dopamine D2 / Q000235:genetics; D050638:Receptors, Dopamine D4; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins
D002352:Carrier Proteins; D000697:Central Nervous System Stimulants; C493599:DRD4 protein, human; D005819:Genetic Markers; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017448:Receptors, Dopamine D2; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D050638:Receptors, Dopamine D4; D008774:Methylphenidate; D011388:Prolactin