Abstract:
:Attention-deficit/hyperactivity disorder (ADHD) is the most common behavioral disorder in childhood with substantial heritability. Pharmacological and molecular genetic studies as well as characterization of animal models have implicated serotonergic dysfunction in the pathophysiology of ADHD. Here, we investigated the effect of polymorphic variants in the gene of the tryptophan hydroxylase-2 (TPH2), the rate-limiting enzyme of serotonin (5-HT) synthesis in the brain, in children and adolescents with ADHD. We analyzed three single nucleotide polymorphisms (SNPs) in and downstream of the transcriptional control region of the TPH2 gene in 103 families with 225 affected children. Allelic association in families with more than one affected child was assessed using the pedigree disequilibrium test. Preferential transmissions were detected for the two SNPs in TPH2's regulatory region (rs4570625, P=0.049; rs11178997, P=0.034), but not for the third SNP in intron 2 (rs4565946, P=0.3517). Haplotype analysis revealed a strong trend of association between the regulatory region SNPs (rs4570625, rs11178997) and ADHD (P=0.064). Our results link potentially functional TPH2 variations to the pathophysiology of ADHD, and further support the relevance of 5-HT in disorders related to altered motor activity and cognitive processes.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Walitza S,Renner TJ,Dempfle A,Konrad K,Wewetzer Ch,Halbach A,Herpertz-Dahlmann B,Remschmidt H,Smidt J,Linder M,Flierl L,Knölker U,Friedel S,Schäfer H,Gross C,Hebebrand J,Warnke A,Lesch KPdoi
10.1038/sj.mp.4001734subject
Has Abstractpub_date
2005-12-01 00:00:00pages
1126-32issue
12eissn
1359-4184issn
1476-5578pii
4001734journal_volume
10pub_type
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