title: Brain-derived neurotrophic factor val66met polymorphism and volume of the hippocampal formation.
abstract: Magnetic resonance (MR) imaging studies have identified hippocampal structural alterations in the pathogenesis of schizophrenia. Brain-derived neurotrophic factor (BDNF) is one of the neurotrophins that is widely expressed in the hippocampal formation and has been implicated in the neurobiology of schizophrenia. Polymorphisms in the BDNF gene may therefore confer risk for schizophrenia through hippocampal pathogenesis and/or making the hippocampus more susceptible to environmental insults. In this study, we investigated whether val66met, a functional and abundant missense polymorphism in the coding region of the BDNF gene, was associated with the volume of the hippocampal formation in 19 patients with first-episode schizophrenia and 25 healthy volunteers. A total of 124 contiguous T1-weighted coronal MR images (slice thickness=1.5 mm) were acquired through the whole head using a 3D Fast SPGR IR Prep sequence on a 1.5 T GE imaging system. Volumes of the right and left hippocampal formation were measured manually by an operator blind to group status and genotype. All participants were genotyped for the BDNF val66met locus. Mixed model analyses revealed a main effect of BDNF val66met genotype such that in the combined sample of patients and healthy volunteers, val/val homozygotes (N=27) had larger volumes of the hippocampal formation compared to val/met heterozygotes (N=17). In separate analyses by group, however, val66met genotype accounted for a greater proportion of the variance in the volume of the hippocampal formation in patients compared to healthy volunteers. These findings implicate genetic involvement of BDNF in variation of human hippocampal volume and suggest that this effect may be greater among patients compared to healthy volunteers.
authors.affiliation: Department of Psychiatry Research, The Zucker Hillside Hospital, North-Shore-Long Island Jewish Health System, Glen Oaks, NY, USA. szeszko@lij.edu
authors.forename: P R
authors.initials: PR
authors.lastname: Szeszko
authors.forename: R
authors.initials: R
authors.lastname: Lipsky
authors.forename: C
authors.initials: C
authors.lastname: Mentschel
authors.forename: D
authors.initials: D
authors.lastname: Robinson
authors.forename: H
authors.initials: H
authors.lastname: Gunduz-Bruce
authors.forename: S
authors.initials: S
authors.lastname: Sevy
authors.forename: M
authors.initials: M
authors.lastname: Ashtari
authors.forename: B
authors.initials: B
authors.lastname: Napolitano
authors.forename: R M
authors.initials: RM
authors.lastname: Bilder
authors.forename: J M
authors.initials: JM
authors.lastname: Kane
authors.forename: D
authors.initials: D
authors.lastname: Goldman
authors.forename: A K
authors.initials: AK
authors.lastname: Malhotra
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D005260:Female; D007839:Functional Laterality; D006624:Hippocampus / Q000473:pathology* / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012016:Reference Values; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology*; D016037:Single-Blind Method; D018709:Statistics, Nonparametric
chemical_list: D019208:Brain-Derived Neurotrophic Factor