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. 2012 Feb;262(1):23-31.
doi: 10.1007/s00406-011-0214-6. Epub 2011 Apr 21.

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

Oliver Gruber  1 , Alkomiet Hasan, Harald Scherk, Thomas Wobrock, Thomas Schneider-Axmann, Savira Ekawardhani, Andrea Schmitt, Martin Backens, Wolfgang Reith, Jobst Meyer, Peter Falkai
Affiliations

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

Oliver Gruber et al. Eur Arch Psychiatry Clin Neurosci. 2012 Feb.

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.

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Figures

Fig. 1
Fig. 1
Magnetic resonance imaging (MRI) demonstrating the localization and well-adapted shape of the volume of interest (voxel size 10 × 35 × 10 mm3) placed in the left hippocampus (MR images in radiological convention) in a transversal, b coronal, and c sagittal orientation
Fig. 2
Fig. 2
Typical proton magnetic resonance spectroscopy spectrum (1H-MRS) from the left hippocampus
Fig. 3
Fig. 3
Significant effects of the functional BDNF val66met polymorphism rs6265 on magnetic resonance spectroscopic markers (a NAA/Cre; b (Glu + Gln)/Cre) in the left hippocampus. *P < 0.05. The y-axis represents the ratios between NAA/Cre and (Glu + Gln)/Cre
See this image and copyright information in PMC

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