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The novel brain-specific tryptophan hydroxylase-2 gene in panic disorder

Department of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany

Christine M. Freitag

Department of Child and Adolescent Psychiatry and Psychotherapy, University of Homburg, Homburg, Germany

Lise Gutknecht

Andreas Reif

Department of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany

Ralf Tauber

Department of Psychiatry, University of Jena, Jena, Germany

Petra Franke

Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany

Jürgen Fritze

Department of Psychiatry and Psychotherapy, University of Frankfurt, Frankfurt, Germany

Gerd Wagner

Gregor Peikert

Berit Wenda

Department of Psychiatry, University of Jena, Jena, Germany

Philipp Sand

Department of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany

Marcella Rietschel

Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany

Henk Garritsen

Institute of Transfusion Medicine and Transplantation Immunology, University of Münster, Münster, Germany

Christian Jacob

K. Peter Lesch

Department of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany

Jürgen Deckert

Department of Psychiatry and Psychotherapy, University of Münster, Münster, Germany

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.

Key Words: panic disorder • agoraphobia • serotonin • tryptophan hydroxylase-2

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