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

I. Massat, D. Souery, J. Del-Favero, M. Nothen, D. Blackwood, W. Muir, R. Kaneva, A. Serretti, C. Lorenzi, M. Rietschel, V. Milanova, G. N. Papadimitriou, D. Dikeos, C. Van Broekhoven, J. Mendlewicz

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)598-605
Number of pages8
JournalMolecular Psychiatry
Volume10
Issue number6
DOIs
Publication statusPublished - Jun 2005

Keywords

  • Age at onset
  • Association study
  • Bipolar disorder
  • Candidate genes
  • Catecholamine neurotransmission
  • COMT gene
  • Major depressive disorder

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health

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