title: Association of the brain-derived neurotrophic factor val66met polymorphism with magnetic resonance spectroscopic markers in the human hippocampus: in vivo evidence for effects on the glutamate system.
abstract: The brain-derived neurotrophic factor (BDNF) is a key regulator of synaptic plasticity and has been suggested to be involved in the pathophysiology and pathogenesis of psychotic disorders, with particular emphasis on dysfunctions of the hippocampus. The aim of the present study was to replicate and to extend prior findings of BDNF val66met genotype effects on hippocampal volume and N-acetyl aspartate (NAA) levels. Hundred and fifty-eight caucasians (66 schizophrenic, 45 bipolar, and 47 healthy subjects; 105 subjects underwent MRI and 103 MRS scanning) participated in the study and were genotyped with regard to the val66met polymorphism (rs6265) of the BDNF gene. Hippocampal volumes were determined using structural magnetic resonance imaging (MRI), and measures of biochemical markers were taken using proton magnetic resonance spectroscopy ((1)H-MRS) in the hippocampus and other brain regions. Verbal memory was assessed as a behavioral index of hippocampal function. BDNF genotype did not impact hippocampal volumes. Significant genotype effects were found on metabolic markers specifically in the left hippocampus. In particular, homozygous carriers of the met-allele exhibited significantly lower NAA/Cre and (Glu + Gln)/Cre metabolic ratios compared with val/val homozygotes, independently of psychiatric diagnoses. BDNF genotype had a numerical, but nonsignificant effect on verbal memory performance. These findings provide first in vivo evidence for an effect of the functional BDNF val66met polymorphism on the glutamate system in human hippocampus.
authors.affiliation: Department of Psychiatry and Psychotherapy, Georg August University Göttingen, Von-Siebold-Strasse 5, 37075, Göttingen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Gruber
authors.forename: Alkomiet
authors.initials: A
authors.lastname: Hasan
authors.forename: Harald
authors.initials: H
authors.lastname: Scherk
authors.forename: Thomas
authors.initials: T
authors.lastname: Wobrock
authors.forename: Thomas
authors.initials: T
authors.lastname: Schneider-Axmann
authors.forename: Savira
authors.initials: S
authors.lastname: Ekawardhani
authors.forename: Andrea
authors.initials: A
authors.lastname: Schmitt
authors.forename: Martin
authors.initials: M
authors.lastname: Backens
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Reith
authors.forename: Jobst
authors.initials: J
authors.lastname: Meyer
authors.forename: Peter
authors.initials: P
authors.lastname: Falkai
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001714:Bipolar Disorder / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003401:Creatine / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008568:Memory / Q000502:physiology; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011522:Protons; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014633:Valine / Q000235:genetics; D014706:Verbal Learning / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D011522:Protons; D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate; D008715:Methionine; D014633:Valine; D003401:Creatine