title: Functional polymorphism within the promotor of the serotonin transporter gene is associated with severe hyperkinetic disorders.
abstract: In children and adolescents, hyperkinetic disorder (HD) with conduct disorder (CD) and without CD and attention-deficit/hyperactivity disorder (ADHD) is known to be comorbid with psychiatric disorders (anxiety, depression, aggression), some of which are related to disturbed serotonergic neurotransmission. The efficiency of serotonergic signalling relates to the concentration of the neurotransmitter in the synaptic cleft and is controlled by the serotonin transporter (5-HTT), which selectively removes serotonin out of the synaptic cleft.(1)The activity of serotonin transport itself has been shown to be also controlled by a 5-HTT-linked polymorphism in its promotor region with a L/L genotype yielding higher levels of 5-HTT function than do L/S or S/S genotypes.(2) Considering an association between 5-HTT polymorphism, serotonergic neurotransmission and HD +/- CD, we genotyped for 5-HTT polymorphism and compared patients with controls. In contrast to the distribution of L/L: L/S: S/S in controls (0.245: 0.509: 0.245), we found an enhanced expression of the L/L genotype in HD patients with CD (0.393: 0.304: 0.304; chi(2) = 7.603; P = 0.0211) and a significant overexpression of L/L in HD without CD (0.542: 0.333: 0.125; chi(2) = 9.127; P = 0.0092). To our knowledge, this is the first finding providing evidence for an association between the 5-HTT polymorphism and hyperkinetic disorder, implying that serotonergic neurotransmission might be affected in this desease. As a consequence, for a successful treatment of these patients one should now also consider drugs which specifically modulate serotonergic signalling such as selective serotonin reuptake inhibitors.
authors.affiliation: Dept of Child and Adolescent Psychiatry, Central Institute of Mental Health Mannheim, Faculty of Clinical Medicine Mannheim of the University of Heidelberg, Germany. Seeger@as200.zi-mannhein.de
authors.forename: G
authors.initials: G
authors.lastname: Seeger
authors.forename: P
authors.initials: P
authors.lastname: Schloss
authors.forename: M H
authors.initials: MH
authors.lastname: Schmidt
mesh_terms: D000293:Adolescent; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D019955:Conduct Disorder / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D006948:Hyperkinesis / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins
chemical_list: D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins