Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta-analysis of case-control studies confirm association to substance-related disorders, eating disorders, and schizophrenia.
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.
Gratacòs
Mònica
M
Genes and Disease Program, Center for Genomic Regulation (CRG), Psychiatry Department, Hospital Universitari de Bellvitge, Barcelona, Spain.
González
Juan R
JR
Mercader
Josep M
JM
de Cid
Rafael
R
Urretavizcaya
Mikel
M
Estivill
Xavier
X
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D016022:Case-Control Studies; D001068:Feeding and Eating Disorders / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000235:genetics*; D008715:Methionine / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012559:Schizophrenia / Q000235:genetics; D019966:Substance-Related Disorders / Q000235:genetics; D014633:Valine / Q000235:genetics*
D019208:Brain-Derived Neurotrophic Factor; D008715:Methionine; D014633:Valine