title: The novel brain-specific tryptophan hydroxylase-2 gene in panic disorder.
abstract: Panic disorder is a common psychiatric disorder characterized by recurrent anxiety attacks and anticipatory anxiety. Due to the severity of the symptoms of the panic attacks and the frequent additional occurrence of agoraphobia, panic disorder is an often debilitating disease. Elevation of central serotonin levels by drugs such as clomipramine represents one of the most effective treatment options for panic disorder. This points to an important role of dysregulation of the serotonergic system in the genetic etiology of panic disorder. The novel brain-specific 5-HT synthesizing enzyme, tryptophan hydroxylase-2 (TPH2), which represents the rate-limiting enzyme of 5-HT production in the brain, may therefore be of particular importance in panic disorder. We focused on the putative transcriptional control region of TPH2 and identified two novel common single nucleotide polymorphisms (SNPs) of TPH2 in and close to this region. Moreover, a recently described loss-of-function mutation of TPH2 which results in an 80% reduction of serotonin production, was assessed. In an analysis of the putative transcriptional control region SNPs in a sample of panic disorder patients and controls no association of the disorder with the TPH2 SNPs or haplotypes was found. Moreover, the loss-of-function R441H mutation of TPH2 was not present in the panic disorder patients. The results of this first study of TPH2 in panic disorder argue against an importance of allelic variation of TPH2 in the pathogenesis of panic disorder with or without agoraphobia.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany. rainald.moessner@mail.uni-wuerzburg.de
authors.forename: Rainald
authors.initials: R
authors.lastname: Mössner
authors.forename: Christine M
authors.initials: CM
authors.lastname: Freitag
authors.forename: Lise
authors.initials: L
authors.lastname: Gutknecht
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
authors.forename: Ralf
authors.initials: R
authors.lastname: Tauber
authors.forename: Petra
authors.initials: P
authors.lastname: Franke
authors.forename: Jürgen
authors.initials: J
authors.lastname: Fritze
authors.forename: Gerd
authors.initials: G
authors.lastname: Wagner
authors.forename: Gregor
authors.initials: G
authors.lastname: Peikert
authors.forename: Berit
authors.initials: B
authors.lastname: Wenda
authors.forename: Philipp
authors.initials: P
authors.lastname: Sand
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Henk
authors.initials: H
authors.lastname: Garritsen
authors.forename: Christian
authors.initials: C
authors.lastname: Jacob
authors.forename: K Peter
authors.initials: KP
authors.lastname: Lesch
authors.forename: Jürgen
authors.initials: J
authors.lastname: Deckert
mesh_terms: D000328:Adult; D000379:Agoraphobia / Q000235:genetics / Q000523:psychology; D000483:Alleles; D019943:Amino Acid Substitution; D001923:Brain Chemistry / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D016584:Panic Disorder / Q000235:genetics* / Q000523:psychology; D011110:Polymorphism, Genetic / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014365:Tryptophan Hydroxylase / Q000235:genetics*
chemical_list: C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase