title: The Val66Met polymorphism of the brain-derived neurotrophic factor gene is associated with risk for psychosis: evidence from a family-based association study.
abstract: Schizophrenia (SZ) is a prevalent and severe mental disorder. One of the most favored hypotheses for the etiology of SZ is the neurodevelopmental hypothesis. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin growth factor family, promotes the development, regeneration, and survival of neurons and has been linked to the neuropathology of SZ. The present study tested, in a sample of 94 nuclear families, the hypothesis that the BDNF gene Val66Met polymorphism is associated to SZ and its psychopathologic phenotype using a multidimensional symptom approach. Furthermore, considering a reported reduction of BDNF in the frontal cortex of patients with SZ, we studied the relationship between this polymorphism and prefrontal function. The transmission disequilibrium test (TDT) showed a preferential transmission of allele Val from heterozygous parents to the affected offspring (P = 0.002), suggesting a possible role of this gene in the vulnerability to SZ spectrum disorders. The findings remained essentially unchanged when the analysis was restricted to the subgroup of patients with SZ (P = 0.009) and when a multidimensional approach to the diagnosis was used. Quantitative transmission disequilibrium test (QTDT) analyses did not demonstrate a significant association between the prefrontal tests assessed (Wisconsin Card Sorting Test and Trail Making Test) and the transmission of the BDNF alleles. Our finding suggests that the investigated BDNF polymorphism plays an important role in the phenotype of psychosis, but not in the performance of tests of prefrontal cognitive functions analyzed in these patients.
authors.affiliation: Unitat d'Antropologia, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain. araceli.rosa@ub.edu
authors.forename: Araceli
authors.initials: A
authors.lastname: Rosa
authors.forename: Manuel J
authors.initials: MJ
authors.lastname: Cuesta
authors.forename: Mar
authors.initials: M
authors.lastname: Fatjó-Vilas
authors.forename: Víctor
authors.initials: V
authors.lastname: Peralta
authors.forename: Amalia
authors.initials: A
authors.lastname: Zarzuela
authors.forename: Lourdes
authors.initials: L
authors.lastname: Fañanás
mesh_terms: D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics*; D000704:Analysis of Variance; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics*; D012565:Schizophrenic Psychology
chemical_list: D019208:Brain-Derived Neurotrophic Factor