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Association between COMT (Val158Met) functional polymorphism and early onset in patients with major depressive disorder in a European multicenter genetic association study

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Abstract

The available data from preclinical and pharmacological studies on the role of the C-O-methyl transferase (COMT) support the hypothesis that abnormal catecholamine transmission has been implicated in the pathogenesis of mood disorders (MD). We examined the relationship of a common functional polymorphism (Val108/158Met) in the COMT gene, which accounts for four-fold variation in enzyme activity, with ‘early-onset’ (EO) forms (less than or equal to 25 years) of MD, including patients with major depressive disorder (EO-MDD) and bipolar patients (EO-BPD), in a European multicenter case–control sample. Our sample includes 378 MDD (120 EO-MDD), 506 BPD (222 EO-BPD) and 628 controls. An association was found between the high-activity COMT Val allele, particularly the COMT Val/Val genotype and EO-MDD. These findings suggest that the COMT Val/Val genotype may be involved in EO-MDD or may be in linkage disequilibrium with a different causative polymorphism in the vicinity. The COMT gene may have complex and pleiotropic effects on susceptibility and symptomatology of neuropsychiatric disorders.

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Acknowledgements

This work was supported by the Association for Mental Health Research (AESM), the European Community Biomed Grant (Grant No CT 92-1217), the National Fund for Scientific Research (NFSR), the Fund for Scientific Research Flanders (FWO) and a concerted action grant of the Special Research Fund of the University of Antwerp, Belgium.

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Authors and Affiliations

  1. Department of Psychiatry, University Clinics of Brussels, Erasme Hospital, Free University of Brussels, Belgium

    I Massat, D Souery & J Mendlewicz

  2. Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB8), University of Antwerp, Antwerpen, Belgium

    J Del-Favero & C Van Broekhoven

  3. Department of Medical Genetics, University of Antwerp, Antwerpen, Belgium

    M Nothen

  4. Department of Psychiatry, School of Molecular and Clinical Medicine, University of Edinburgh, UK

    D Blackwood & W Muir

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

    R Kaneva

  6. Department of Psychiatry, Vita-Salute University, San Raffaele Institute, Milan, Italy

    A Serretti & C Lorenzi

  7. Central Institute of Mental Health, Mannheim, Germany

    M Rietschel

  8. First Psychiatric Clinic, Department of Psychiatry, Alexander University Hospital, Sofia, Bulgaria

    V Milanova

  9. Athens University Medical School, Department of Psychiatry and University Mental Health Research Institute, Athens, Greece

    G N Papadimitriou & D Dikeos

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  1. I Massat
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Massat, I., Souery, D., Del-Favero, J. et al. Association between COMT (Val158Met) functional polymorphism and early onset in patients with major depressive disorder in a European multicenter genetic association study. Mol Psychiatry 10, 598–605 (2005). https://doi.org/10.1038/sj.mp.4001615

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