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Forschungsdatenbank der Universität Zürich
Medizinische Fakultät > Psychiatrische Universitätsklinik > Kinder- und Jugendpsychiatrie und
Psychotherapie, Klinik für > Prof. Dr. Susanne Walitza
Genetic studies in early onset obsessive-compulsive disorders
Original title / Originaltitel
Genetische Untersuchungen bei Zwangsstörungen im Kindes- und Jugendalter
Summary / Zusammenfassung
Obsessive compulsive disorder (OCD) is a genetically complex disorder with high heritability.
Several genetic components are supposed to contribute to its pathophysiology. In particular
serotonergic and dopaminergic genes are the focus of investigation, endorsed by clinical efficacy
of SSRI and atypical neuroleptics. In our studies serotonergic and dopaminergic genes were
investigated for association with OCD in a case-control-study and in a family based sample. A
multicenter study we are also part of the first genome-wide association study in OCD. In our own
sample association between the serotonergic genes TPH2, 5HT2A as well as between DRD4 by
early onset OCD was found by applying the Transmission Disequilibrium Test (TDT). In the
investigated family based sample consisting of children with early-onset OCD several genes
influencing monoaminergic neurotransmission were found to be associated with OCD. By this
finding further evidence for the crucial role of serotonergic effectors for the pathophysiology of
OCD is provided. Positive association was also detected between DRD4 and OCD, endorsing the
discussion about the special role of the dopaminergic for early onset OCD. Further investigation
on early onset OCD will further investigate for occurrence of copy number variations (CNVs) and
their functional effects.
Publications / Publikationen
Original-Arbeiten
Walitza S, Wewetzer C, Warnke A, Gerlach M, Geller F, Goerg T, Gerber G, Herpertz-Dahlmann
B, Schulz E, Remschmidt H, Hebebrand J, Hinney A (2002) 5-HT2A promoter polymorphism
-1438G/A in children and adolescents with obsessive-compulsive disorders. Mol Psychiatry, 7:
1054-1057
Walitza S, Wewetzer C, Gerlach M, Klampfl K, Geller F, Barth N, Hahn F, Herpertz-Dahlmann
B, Gössler M, Fleischhaker C, Schulz E, Hebebrand J , Warnke A, Hinney A (2004)
Transmission disequilibrium studies in children and adolescents with obsessive-compulsive
disorders pertaining to polymorphisms of genes of the serotonergic pathway. J Neural Transm,
111: 817-825
Mössner R, Walitza S, Lesch K-P, Geller F, Barth N, Remschmidt H, Hahn F, Herpertz-Dahlmann
B, Fleischhaker Ch, Schulz E, Warnke A, Hinney A, Wewetzer C (2004). Brain-derived
neurotrophic factor V66M polymorphism in childhood-onset obsessive-compulsive disorder. Int J
Neuropsychopharmacol, 8: 1-4
Mössner R, Walitza S, Geller F, Scherag A, Bogusch L, Remschmidt H, Simons M, HerpertzDahlmann B, Fleischhaker C, Schulz E, Warnke A, Hinney A , Wewetzer C, Lesch, K-P (2005)
Linkage disequilibrium of polymorphisms in the brain-specific tryptophan hydroxylase-2 gene in
children and adolescents with obsessive-compulsive disorder. Int J Neuropsychopharmacol 7:1-6
Renner T, Walitza S (2006) Schwere frühkindliche Zwangsstörung: Kasuistik eines 4-jährigen
Mädchens. Z Kinder Jugendpsychiatr, 34:287-93
Mössner R, Döring N, Scherag A, Schäfer H, Herpertz-Dahlmann B, Remschmidt H, Schulz E,
Renner T, Wewetzer C, Warnke A, Lesch KP, Walitza S (2007). Transmission disequilibrium
analysis of the functional 5-HT3A receptor variant C178T in early-onset obsessive-compulsive
Project 11963
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disorder. J Psychopharmacol Jan 26, 2007 Epub ahead of print
Lazar A, Walitza S , Jetter A Gerlach M, Warnke A, Herpertz-Dahlmann B, Gründemann D,
Taubert D, Schulz E, Remschmidt H, Wewetzer Ch, Schömig E (2007): Novel mutations of the
extraneuronal monoamine transporter gene in children and adolescents with obsessive-compulsive
disorder. Int J Neuropsychopharmacol, 4: 1-14
Walitza S, Zellmann H, Irblich B, Lange KW, Tucha O, Hemminger U, Wucherer K, Rost V,
Reinecker H, Wewetzer C, Warnke A. Children and adolescents with obsessive-compulsive
disorder and comorbid attention-deficit/hyperactivity disorder: preliminary results of a prospective
follow-up study. J Neural Transm. 2008;115(2):187-90. Epub 2008 Jan 16.
Walitza S, Renner, T. J., Wewetzer, C., Warnke A (2008) Genetische Befunde bei
Zwangsstörungen im Kindes- und Jugendalter und bei Erwachsenen. Zeitschrift für Kinder- und
Jugendpsychiatrie und Psychotherapie, 36, 45-52.
Walitza S, Scherag A, Renner TJ, Hinney A, Remschmidt H, Herpertz-Dahlmann B, Schulz E,
Schafer H, Lange KW, Wewetzer C, Gerlach M. Transmission disequilibrium studies in early
onset of obsessive-compulsive disorder for polymorphisms in genes of the dopaminergic system. J
Neural Transm. 2008 Apr 30. Epub ahead of print.
Zellmann H, Jans T., Irblich B, Hemminger U, Reinecker H, Sauer C, Warnke A, Walitza S. Der
mittelfristige Verlauf von Zwangsstörungen mit Beginn im Kindes- und Jugendalter: Aspekte der
Psychosozialen Anpassung. Verhaltenstherapie & Verhaltensmedizin, 29, 336-351.
Zellmann H, Jans T, Irblich B, Hemminger U, Reinecker H, Sauer C, Lange K, Wewetzer Ch,
Warnke A, Walitza S. Kinder und Jugendliche mit Zwangsstörungen: Eine prospektive
Verlaufsstudie. Zeitschrift für KJPP in press 3/2009.
Walitza S, Sabanés Bové D, Romanos M, Renner T, Held L, Simons M, Wewetzer C, Fleischhaker
C, Remschmidt H, Warnke A, Grünblatt E (2012) Pilot study on HTR2A promoter polymorphism,
–1438G/A (rs6311) and a nearby copy number variation showed association with onset and
severity in early-onset obsessive-compulsive disorder. J Neural Transm. 119(4): 507-515.
Übersichtsarbeiten
Wewetzer Ch, Walitza S (2005) Kombinierte Therapie bei Zwangsstörungen im Kindes- und
Jugendalter. MMW-Fortschritte der Medizin, 36: 989-993.
Walitza S, Renner T (2006): Genetik bei Zwangsstörungen im Kindes- und Jugendalter. Med Gen,
18: 47-50.
Walitza S, Renner TJ, Wewetzer Ch (2008) Warnke A. Genetische Befunde bei Zwangsstörungen
im Kindes- und Jugendalter und bei Erwachsenen. Z Kinder Jugendpsychiatr 36(1):45-52
Keywords / Suchbegriffe
early onset OCD, child and adolescent psychiatry, genetics
Project Leadership and Contacts / Projektleitung und Kontakte
Prof. Susanne Walitza, M.Sc., M.D. (Project Leader)
[email protected]
Dr. Juliane Ball (Project Leader)[email protected]
Dr. Edna Grünblatt (Project Leader)
[email protected]
Funding Source(s) / Unterstützt durch
Others
In Collaboration with / In Zusammenarbeit mit
Prof. Marcel Romanos
Project 11963
Germany
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Prof. Klaus-Peter Lesch
Universitätsklinik Würzburg
Kliniken für Kinder- ud Jugendpsychiatrie und Psychiatrie
Universität Würzburg
Dr. Jens Wendland
Laboratory of Clinical Science
NIMH Intramural Research Program, NIH
Prof. Anita Rauch
Universität Zürich
Schweiz
United States
Switzerland
Duration of Project / Projektdauer
Jan 2002 to Dec 2015
Project 11963
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