Brain-Derived Neurotrophic Factor Val66Met and Psychiatric Disorders: Meta-Analysis of Case-Control Studies Confirm Association to Substance-Related Disorders, Eating Disorders, and Schizophrenia

Mònica Gratacòs, Juan R. González, Josep M. Mercader, Rafael de Cid, Mikel Urretavizcaya, Xavier P. Estivill

Research output: Contribution to journalArticle

304 Citations (Scopus)

Abstract

Background: There is an increasing recognition that the pathophysiology of mental disorders could be the result of deregulation of synaptic plasticity with alterations of neurotrophins. The valine (Val)66-to-methionine (Met) variant, located in the pro brain-derived neurotrophic factor (BDNF) sequence, has been extensively studied through linkage and association approaches in several psychiatric disorders. Methods: We performed a meta-analysis restricted to individual case-control studies in different categories of mental disorders and BDNF Val66Met polymorphism. We included data from 39 case-control studies encompassing psychiatric phenotypes: eating disorders, substance-related disorders, mood disorders, and schizophrenia, among others. Results: The association of Val66Met was confined to three diagnoses: substance-related disorders, eating disorders, and schizophrenia. The Val/Met and the Met/Met genotypes increase the risk for eating disorders up to 33%, while these same genotypes confer a 21% protective effect in substance-related disorders. The homozygous carriers Met/Met showed a 19% increased risk of schizophrenia with respect to the heterozygous state. Conclusions: The study confirms the association of Val66Met to substance-related disorders, eating disorders, and schizophrenia. It remains to be determined if other variants in tight linkage disequilibrium with Val66Met could configure an extended functional haplotype that would explain observed discrepancies in risk estimations across studies.

Original languageEnglish
Pages (from-to)911-922
Number of pages12
JournalBiological Psychiatry
Volume61
Issue number7
DOIs
Publication statusPublished - 1 Apr 2007
Externally publishedYes

Fingerprint

Brain-Derived Neurotrophic Factor
Substance-Related Disorders
Psychiatry
Meta-Analysis
Case-Control Studies
Schizophrenia
Valine
Mental Disorders
Genotype
Neuronal Plasticity
Linkage Disequilibrium
Nerve Growth Factors
Mood Disorders
Methionine
Haplotypes
Phenotype
Feeding and Eating Disorders

Keywords

  • BDNF
  • eating disorders
  • meta-analysis
  • schizophrenia
  • substance-related disorders
  • Val66Met

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Brain-Derived Neurotrophic Factor Val66Met and Psychiatric Disorders : Meta-Analysis of Case-Control Studies Confirm Association to Substance-Related Disorders, Eating Disorders, and Schizophrenia. / Gratacòs, Mònica; González, Juan R.; Mercader, Josep M.; de Cid, Rafael; Urretavizcaya, Mikel; Estivill, Xavier P.

In: Biological Psychiatry, Vol. 61, No. 7, 01.04.2007, p. 911-922.

Research output: Contribution to journalArticle

@article{c76d1c5fab594fafa19fc213cdedcc8a,
title = "Brain-Derived Neurotrophic Factor Val66Met and Psychiatric Disorders: Meta-Analysis of Case-Control Studies Confirm Association to Substance-Related Disorders, Eating Disorders, and Schizophrenia",
abstract = "Background: There is an increasing recognition that the pathophysiology of mental disorders could be the result of deregulation of synaptic plasticity with alterations of neurotrophins. The valine (Val)66-to-methionine (Met) variant, located in the pro brain-derived neurotrophic factor (BDNF) sequence, has been extensively studied through linkage and association approaches in several psychiatric disorders. Methods: We performed a meta-analysis restricted to individual case-control studies in different categories of mental disorders and BDNF Val66Met polymorphism. We included data from 39 case-control studies encompassing psychiatric phenotypes: eating disorders, substance-related disorders, mood disorders, and schizophrenia, among others. Results: The association of Val66Met was confined to three diagnoses: substance-related disorders, eating disorders, and schizophrenia. The Val/Met and the Met/Met genotypes increase the risk for eating disorders up to 33{\%}, while these same genotypes confer a 21{\%} protective effect in substance-related disorders. The homozygous carriers Met/Met showed a 19{\%} increased risk of schizophrenia with respect to the heterozygous state. Conclusions: The study confirms the association of Val66Met to substance-related disorders, eating disorders, and schizophrenia. It remains to be determined if other variants in tight linkage disequilibrium with Val66Met could configure an extended functional haplotype that would explain observed discrepancies in risk estimations across studies.",
keywords = "BDNF, eating disorders, meta-analysis, schizophrenia, substance-related disorders, Val66Met",
author = "M{\`o}nica Gratac{\`o}s and Gonz{\'a}lez, {Juan R.} and Mercader, {Josep M.} and {de Cid}, Rafael and Mikel Urretavizcaya and Estivill, {Xavier P.}",
year = "2007",
month = "4",
day = "1",
doi = "10.1016/j.biopsych.2006.08.025",
language = "English",
volume = "61",
pages = "911--922",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier USA",
number = "7",

}

TY - JOUR

T1 - Brain-Derived Neurotrophic Factor Val66Met and Psychiatric Disorders

T2 - Meta-Analysis of Case-Control Studies Confirm Association to Substance-Related Disorders, Eating Disorders, and Schizophrenia

AU - Gratacòs, Mònica

AU - González, Juan R.

AU - Mercader, Josep M.

AU - de Cid, Rafael

AU - Urretavizcaya, Mikel

AU - Estivill, Xavier P.

PY - 2007/4/1

Y1 - 2007/4/1

N2 - Background: There is an increasing recognition that the pathophysiology of mental disorders could be the result of deregulation of synaptic plasticity with alterations of neurotrophins. The valine (Val)66-to-methionine (Met) variant, located in the pro brain-derived neurotrophic factor (BDNF) sequence, has been extensively studied through linkage and association approaches in several psychiatric disorders. Methods: We performed a meta-analysis restricted to individual case-control studies in different categories of mental disorders and BDNF Val66Met polymorphism. We included data from 39 case-control studies encompassing psychiatric phenotypes: eating disorders, substance-related disorders, mood disorders, and schizophrenia, among others. Results: The association of Val66Met was confined to three diagnoses: substance-related disorders, eating disorders, and schizophrenia. The Val/Met and the Met/Met genotypes increase the risk for eating disorders up to 33%, while these same genotypes confer a 21% protective effect in substance-related disorders. The homozygous carriers Met/Met showed a 19% increased risk of schizophrenia with respect to the heterozygous state. Conclusions: The study confirms the association of Val66Met to substance-related disorders, eating disorders, and schizophrenia. It remains to be determined if other variants in tight linkage disequilibrium with Val66Met could configure an extended functional haplotype that would explain observed discrepancies in risk estimations across studies.

AB - Background: There is an increasing recognition that the pathophysiology of mental disorders could be the result of deregulation of synaptic plasticity with alterations of neurotrophins. The valine (Val)66-to-methionine (Met) variant, located in the pro brain-derived neurotrophic factor (BDNF) sequence, has been extensively studied through linkage and association approaches in several psychiatric disorders. Methods: We performed a meta-analysis restricted to individual case-control studies in different categories of mental disorders and BDNF Val66Met polymorphism. We included data from 39 case-control studies encompassing psychiatric phenotypes: eating disorders, substance-related disorders, mood disorders, and schizophrenia, among others. Results: The association of Val66Met was confined to three diagnoses: substance-related disorders, eating disorders, and schizophrenia. The Val/Met and the Met/Met genotypes increase the risk for eating disorders up to 33%, while these same genotypes confer a 21% protective effect in substance-related disorders. The homozygous carriers Met/Met showed a 19% increased risk of schizophrenia with respect to the heterozygous state. Conclusions: The study confirms the association of Val66Met to substance-related disorders, eating disorders, and schizophrenia. It remains to be determined if other variants in tight linkage disequilibrium with Val66Met could configure an extended functional haplotype that would explain observed discrepancies in risk estimations across studies.

KW - BDNF

KW - eating disorders

KW - meta-analysis

KW - schizophrenia

KW - substance-related disorders

KW - Val66Met

UR - http://www.scopus.com/inward/record.url?scp=33947235663&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33947235663&partnerID=8YFLogxK

U2 - 10.1016/j.biopsych.2006.08.025

DO - 10.1016/j.biopsych.2006.08.025

M3 - Article

C2 - 17217930

AN - SCOPUS:33947235663

VL - 61

SP - 911

EP - 922

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 7

ER -