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 journalArticle

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

Fingerprint

Major Depressive Disorder
Genetic Association Studies
Transferases
Mood Disorders
Genotype
Linkage Disequilibrium
Genes
Catecholamines
Alleles
Pharmacology
Enzymes

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

Cite this

Association between COMT (Val158Met) functional polymorphism and early onset in patients with major depressive disorder in a European multicenter genetic association study. / Massat, I.; Souery, D.; Del-Favero, J.; Nothen, M.; Blackwood, D.; Muir, W.; Kaneva, R.; Serretti, A.; Lorenzi, C.; Rietschel, M.; Milanova, V.; Papadimitriou, G. N.; Dikeos, D.; Van Broekhoven, C.; Mendlewicz, J.

In: Molecular Psychiatry, Vol. 10, No. 6, 06.2005, p. 598-605.

Research output: Contribution to journalArticle

Massat, I, Souery, D, Del-Favero, J, Nothen, M, Blackwood, D, Muir, W, Kaneva, R, Serretti, A, Lorenzi, C, Rietschel, M, Milanova, V, Papadimitriou, GN, Dikeos, D, Van Broekhoven, C & Mendlewicz, J 2005, 'Association between COMT (Val158Met) functional polymorphism and early onset in patients with major depressive disorder in a European multicenter genetic association study', Molecular Psychiatry, vol. 10, no. 6, pp. 598-605. https://doi.org/10.1038/sj.mp.4001615
Massat, I. ; Souery, D. ; Del-Favero, J. ; Nothen, M. ; Blackwood, D. ; Muir, W. ; Kaneva, R. ; Serretti, A. ; Lorenzi, C. ; Rietschel, M. ; Milanova, V. ; Papadimitriou, G. N. ; Dikeos, D. ; Van Broekhoven, C. ; Mendlewicz, J. / Association between COMT (Val158Met) functional polymorphism and early onset in patients with major depressive disorder in a European multicenter genetic association study. In: Molecular Psychiatry. 2005 ; Vol. 10, No. 6. pp. 598-605.
@article{d2b53c09922d46419cd5e3db5701524e,
title = "Association between COMT (Val158Met) functional polymorphism and early onset in patients with major depressive disorder in a European multicenter genetic association study",
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.",
keywords = "Age at onset, Association study, Bipolar disorder, Candidate genes, Catecholamine neurotransmission, COMT gene, Major depressive disorder",
author = "I. Massat and D. Souery and J. Del-Favero and M. Nothen and D. Blackwood and W. Muir and R. Kaneva and A. Serretti and C. Lorenzi and M. Rietschel and V. Milanova and Papadimitriou, {G. N.} and D. Dikeos and {Van Broekhoven}, C. and J. Mendlewicz",
year = "2005",
month = "6",
doi = "10.1038/sj.mp.4001615",
language = "English",
volume = "10",
pages = "598--605",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Association between COMT (Val158Met) functional polymorphism and early onset in patients with major depressive disorder in a European multicenter genetic association study

AU - Massat, I.

AU - Souery, D.

AU - Del-Favero, J.

AU - Nothen, M.

AU - Blackwood, D.

AU - Muir, W.

AU - Kaneva, R.

AU - Serretti, A.

AU - Lorenzi, C.

AU - Rietschel, M.

AU - Milanova, V.

AU - Papadimitriou, G. N.

AU - Dikeos, D.

AU - Van Broekhoven, C.

AU - Mendlewicz, J.

PY - 2005/6

Y1 - 2005/6

N2 - 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.

AB - 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.

KW - Age at onset

KW - Association study

KW - Bipolar disorder

KW - Candidate genes

KW - Catecholamine neurotransmission

KW - COMT gene

KW - Major depressive disorder

UR - http://www.scopus.com/inward/record.url?scp=21244485041&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=21244485041&partnerID=8YFLogxK

U2 - 10.1038/sj.mp.4001615

DO - 10.1038/sj.mp.4001615

M3 - Article

C2 - 15583702

AN - SCOPUS:21244485041

VL - 10

SP - 598

EP - 605

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 6

ER -