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 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.
Stern
Alexa J
AJ
Clinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, National Institute of Mental Health Intramural Research Program, National Institutes of Health, Bethesda, Maryland 20892, USA.
Savostyanova
Antonina A
AA
Goldman
Aaron
A
Barnett
Alan S
AS
van der Veen
Jan Willem C
JW
Callicott
Joseph H
JH
Mattay
Venkata S
VS
Weinberger
Daniel R
DR
Marenco
Stefano
S
D000328:Adult; D000704:Analysis of Variance; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D016009:Chi-Square Distribution; D002794:Choline; D003401:Creatine; D005260:Female; D007839:Functional Laterality; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008715:Methionine / Q000235:genetics*; D011110:Polymorphism, Genetic; D014633:Valine / Q000235:genetics*; D055815:Young Adult
D019208:Brain-Derived Neurotrophic Factor; D001224:Aspartic Acid; C000179:N-acetylaspartate; D008715:Methionine; D014633:Valine; D003401:Creatine; D002794:Choline