The novel brain-specific tryptophan hydroxylase-2 gene in panic disorder
Rainald Mossner1*,
Christine M. Freitag2,
Lise Gutknecht1,
Andreas Reif1,
Ralf Tauber3,
Petra Franke4,
Jurgen Fritze5,
Gerd Wagner3,
Gregor Peikert3,
Berit Wenda3,
Philipp Sand1,
Marcella Rietschel4,
Henk Garritsen6,
Christian Jacob1,
K. Peter Lesch1,
Jurgen Deckert7
1 Department of Psychiatry and Psychotherapy, University of
Würzburg, Würzburg, Germany
2 Department of Child and Adolescent Psychiatry and Psychotherapy,
University of Homburg, Homburg, Germany
3 Department of Psychiatry, University of Jena, Jena, Germany
4 Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany
5 Department of Psychiatry and Psychotherapy, University of Frankfurt,
Frankfurt, Germany
6 Institute of Transfusion Medicine and Transplantation Immunology,
University of Münster, Münster, Germany
7 Department of Psychiatry and Psychotherapy, University of
Münster, Münster, Germany
* To whom correspondence should be addressed.
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Abstract |
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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
