1. ¹Department of Psychiatry, University Clinics of Brussels, Erasme Hospital, Free University of Brussels, Belgium
2. ²Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB8), University of Antwerp, Antwerpen, Belgium
3. ³Department of Medical Genetics, University of Antwerp, Antwerpen, Belgium
4. ⁴Department of Psychiatry, School of Molecular and Clinical Medicine, University of Edinburgh, UK
5. ⁵Laboratory of Molecular Pathology, University Hospital of Obstetrics, Medical University, Sofia, Bulgaria
6. ⁶Department of Psychiatry, Vita-Salute University, San Raffaele Institute, Milan Italy
7. ⁷Central Institute of Mental Health, Mannheim, Germany
8. ⁸First Psychiatric Clinic, Department of Psychiatry, Alexander University Hospital, Sofia, Bulgaria
9. ⁹Athens University Medical School, Department of Psychiatry and University Mental Health Research Institute, Athens, Greece

Correspondence: Dr I Massat, Department of Psychiatry, Unit of Adolescents, University Clinics of Brussels, Erasme Hospital, Free University of Brussels, Route de Lennik 808, B-1070, Brussels, Belgium. E-mail: imassat@ulb.ac.be

Received 30 December 2003; Revised 14 September 2004; Accepted 23 September 2004; Published online 7 December 2004.

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.