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HTR2C (cys23ser) polymorphism influences early onset in bipolar patients in a large European multicenter association study

Molecular Psychiatry volume 12, pages 797–798 (2007)Cite this article

Bipolar disorder (BP) is a multifactorial disease with complex inheritance. Inconsistencies of results of genetic studies are probably due in part to the heterogeneity of the disorder. We showed that a structural variant (cys23ser) of the serotonin 2C receptor gene (HTR2C) may be involved in ‘early onset’ phenotype of BP (EO-BP), supporting the notion that specific clinical indicators of BP, such as age at onset (AAO), may contribute to identify specific genetic vulnerability factors.

In a second step, to assess whether AAO variation reflected the underlying genetic heterogeneity in BP, we examined the relationship of the HTR2C (cys23ser) polymorphism (on chromosome Xq24) with EO-BP (cutoff of 16 years) in a subsample of BP patients previously reported by our group,5 including 625 BP (of whom 66 were EO-BP) and 829 controls, recruited in eight collaborative centers (Athens, Bonn, Brussels, Edinburgh, Jerusalem, Milan, Sofia, Zagreb). All subjects were assessed by using criteria identified at standard diagnostic interviews, according to the DSM-IV.4, 6 AAO was defined on the basis of self-report as the age at first episode of mania or depression that met diagnostic DSM-IV criteria.6 Local ethical committees approved the study, and written informed consent was obtained from all subjects.

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Authors and Affiliations

  1. Department of Psychiatry, University Clinics of Brussels, Erasme Hospital, Free University of Brussels (ULB), Research Associate of FNRS (Fund for Scientific Research), Brussels, Belgium

    I Massat, D Souery & J Mendlewicz

  2. Biological Psychiatry Laboratory, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

    B Lerer

  3. Division of Psychiatry, University of Edinburgh, Edinburgh, UK

    D Blackwood & W Muir

  4. Laboratory of Molecular Pathology, University Hospital of Obstetrics, Medical University, Sofia, Bulgaria

    R Kaneva

  5. Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany

    M M Nöthen

  6. Institute of Human Genetics, University of Bonn, Bonn, Germany

    M M Nöthen

  7. Psychiatric Clinic, Clinical Centre, University of Sarajevo, Sarajevo, Bosnia and Herzegovina

    L Oruc

  8. Department of Psychiatry, University Mental Health Research Institute,

    G N Papadimitriou & D Dikeos

  9. Athens University Medical School, Athens, Greece

    G N Papadimitriou & D Dikeos

  10. Department of Psychiatry, San Raffaele Scientific Institute,

    A Serretti

  11. Vita-Salute University, Milan, Italy

    A Serretti

  12. Institute of Psychiatry, University of Bologna, Bologna, Italy,

    A Serretti

  13. Unité Neurobiologie et Psychiatrie (INSERM U513), Faculté de médecine de Créteil, Créteil, France

    F Bellivier

  14. Service de Psychiatrie, Hôpital Henry Mondor et Albert Chenevier, Assistance Publique-Hôpitaux de Paris, Créteil, France

    F Bellivier

  15. Department of Biostatistics (EA3974), University Paris VI, Paris, France,

    J L Golmard

  16. Department of Psychiatry, Alexander University Hospital, Medical University, Sofia, Bulgaria

    V Milanova

  17. Department of Molecular Genetics, Applied Molecular Genomics Group, Flanders Interuniversity Institute for Biotechnology, Antwerpen, Belgium

    J Del-Favero

  18. University of Antwerp, Antwerpen, Belgium

    J Del-Favero & C Van Broeckhoven

  19. Department of Molecular Genetics, Neurodegenerative Brain Diseases Group, Flanders Interuniversity Institute for Biotechnology, Antwerpen, Belgium

    C Van Broeckhoven

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  1. I Massat
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  17. J Mendlewicz
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Correspondence to I Massat.

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Massat, I., Lerer, B., Souery, D. et al. HTR2C (cys23ser) polymorphism influences early onset in bipolar patients in a large European multicenter association study. Mol Psychiatry 12, 797–798 (2007). https://doi.org/10.1038/sj.mp.4002018

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