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.
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.
Authors: Gudmar Thorleifsson; G Bragi Walters; Daniel F Gudbjartsson; Valgerdur Steinthorsdottir; Patrick Sulem; Anna Helgadottir; Unnur Styrkarsdottir; Solveig Gretarsdottir; Steinunn Thorlacius; Ingileif Jonsdottir; Thorbjorg Jonsdottir; Elinborg J Olafsdottir; Gudridur H Olafsdottir; Thorvaldur Jonsson; Frosti Jonsson; Knut Borch-Johnsen; Torben Hansen; Gitte Andersen; Torben Jorgensen; Torsten Lauritzen; Katja K Aben; André L M Verbeek; Nel Roeleveld; Ellen Kampman; Lisa R Yanek; Lewis C Becker; Laufey Tryggvadottir; Thorunn Rafnar; Diane M Becker; Jeffrey Gulcher; Lambertus A Kiemeney; Oluf Pedersen; Augustine Kong; Unnur Thorsteinsdottir; Kari Stefansson Journal: Nat Genet Date: 2008-12-14 Impact factor: 38.330
Authors: Danielle L Graham; Vaishnav Krishnan; Erin B Larson; Ami Graham; Scott Edwards; Ryan K Bachtell; Diana Simmons; Lana M Gent; Olivier Berton; Carlos A Bolanos; Ralph J DiLeone; Luis F Parada; Eric J Nestler; David W Self Journal: Biol Psychiatry Date: 2008-11-06 Impact factor: 13.382
Authors: Cherubino Di Lorenzo; Giorgio Di Lorenzo; Grazia Sances; Natascia Ghiotto; Elena Guaschino; Gaetano S Grieco; Filippo M Santorelli; Carlo Casali; Alfonso Troisi; Alberto Siracusano; Francesco Pierelli Journal: J Headache Pain Date: 2009-06-11 Impact factor: 7.277