Impact of the Brain-Derived Neurotrophic Factor Val66Met Polymorphism on Levels of Hippocampal N -Acetyl-Aspartate Assessed by Magnetic Resonance Spectroscopic Imaging at 3 Tesla

Impact of the Brain-Derived Neurotrophic Factor Val66Met Polymorphism on Levels of Hippocampal N -Acetyl-Aspartate Assessed by Magnetic Resonance Spectroscopic Imaging at 3 Tesla

Background This study was conducted to corroborate prior evidence of an effect of the brain-derived neurotrophic factor (BDNF) valine (val) to methionine (met) amino acid substitution at codon 66 (val66met) polymorphism on measures of N -acetyl-aspartate (NAA) containing compounds in healthy subject...

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Bibliographic Details
Published in:Biological psychiatry (1969) Vol. 64; no. 10; pp. 856 - 862
Main Authors: Stern, Alexa J, Savostyanova, Antonina A, Goldman, Aaron, Barnett, Alan S, van der Veen, Jan Willem C, Callicott, Joseph H, Mattay, Venkata S, Weinberger, Daniel R, Marenco, Stefano
Format: Journal Article
Language:English
Published: New York, NY Elsevier Inc 15-11-2008
Elsevier Science
Subjects:
Adult
Aging
Analysis of Variance
Aspartic Acid - analogs & derivatives
Aspartic Acid - metabolism
Biological and medical sciences
Brain-Derived Neurotrophic Factor - genetics
Brain-Derived Neurotrophic Factor - metabolism
Chi-Square Distribution
Choline
Creatine
Female
Functional Laterality
gray matter
healthy
hippocampal volume
Hippocampus - metabolism
Humans
Magnetic Resonance Spectroscopy
Male
Medical sciences
Methionine - genetics
Polymorphism, Genetic
Psychiatry
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Valine - genetics
Young Adult
Aging
IQ
choline
hippocampal volume
healthy
gray matter
Choleretic
Volumetric analysis
Senescence
Central nervous system
Cognition
Genetic determinism
Encephalon
Genetics
Intellectual ability
Brain derived neurotrophic factor
Grey matter
Aspartate
Nuclear magnetic resonance imaging
Choline
Excitatory aminoacid
Neurotransmitter
Medical imagery
Hippocampus
Polymorphism
Intelligence quotient
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Summary:Background This study was conducted to corroborate prior evidence of an effect of the brain-derived neurotrophic factor (BDNF) valine (val) to methionine (met) amino acid substitution at codon 66 (val66met) polymorphism on measures of N -acetyl-aspartate (NAA) containing compounds in healthy subjects. Methods The NAA to creatine (Cre) ratio (NAA/Cre), NAA to choline (Cho) ratio (NAA/Cho), and Cho to Cre ratio (Cho/Cre) were measured in the left and right hippocampi, left and right dorsolateral prefrontal cortices, occipital lobe, anterior cingulate, and white matter of the centrum semiovale of 69 carefully screened healthy volunteers utilizing proton magnetic resonance spectroscopic imaging (MRSI) at 3 Tesla (T). Results Val/met subjects exhibited significantly reduced levels of left hippocampal NAA/Cre and NAA/Cho compared with val/val subjects. This effect was independent of age, IQ, number of voxels, hippocampal volume, or gray matter content in the voxels of interest. Analysis of other brain regions showed no effect of BDNF genotype on NAA measures. Conclusions We confirmed the association between the met-BDNF variant and reduced levels of hippocampal NAA found with a similar technique at 1.5T. The consonance of our results with prior findings adds to the evidence that the BDNF val/met genotype affects hippocampal biology with implications for a variety of neuropsychiatric disorders.
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ISSN:0006-3223
1873-2402
DOI:10.1016/j.biopsych.2008.07.009