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  Met carriers of the BDNF Val66Met polymorphism show reduced Glx/NAA in the pregenual ACC in two independent cohorts

Martens, L., Herrmann, L., Colic, L., Li, M., Richter, A., Behnisch, G., et al. (2021). Met carriers of the BDNF Val66Met polymorphism show reduced Glx/NAA in the pregenual ACC in two independent cohorts. Scientific Reports, 11(1): 6742, pp. 1-12. doi:10.1038/s41598-021-86220-3.

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Martens, L1, 2, Author           
Herrmann, L, Author
Colic, L, Author
Li, M, Author           
Richter, A, Author
Behnisch, G, Author
Stork, O, Author
Seidenbecher, C, Author
Schott, BH, Author
Walter, M, Author           
Affiliations:
1Department High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_1497796              
2Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_1497794              

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 Abstract: The Met allele of the Val66Met SNP of the BDNF gene (rs6265) is associated with impaired activity-dependent release of brain-derived neurotrophic factor (BDNF), resulting in reduced synaptic plasticity, impaired glutamatergic neurotransmission, and morphological changes. While previous work has demonstrated Val66Met effects on magnetic resonance spectroscopy (MRS) markers of either glutamatergic metabolism (Glx) or neuronal integrity (NAA), no study has investigated Val66Met effects on these related processes simultaneously. As these metabolites share a metabolic pathway, the Glx/NAA ratio may be a more sensitive marker of changes associated with the Val66Met SNP. This ratio is increased in psychiatric disorders linked to decreased functioning in the anterior cingulate cortex (ACC). In this study, we investigated the correlation of the Val66Met polymorphism of the BDNF gene with Glx/NAA in the pregenual anterior cingulate cortex (pgACC) using MRS at 3 Tesla (T) (n = 30, all males) and 7 T (n = 98, 40 females). In both cohorts, Met carriers had lower Glx/NAA compared to Val homozygotes. Follow-up analyses using absolute quantification revealed that the Met carriers do not show decreased pgACC glutamate or glutamine levels, but instead show increased NAA compared to the Val homozygotes. This finding may in part explain conflicting evidence for Val66Met as a risk factor for developing psychiatric illnesses.

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 Dates: 2021-03
 Publication Status: Published online
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 Identifiers: DOI: 10.1038/s41598-021-86220-3
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Title: Scientific Reports
  Abbreviation : Sci. Rep.
Source Genre: Journal
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Publ. Info: London, UK : Nature Publishing Group
Pages: - Volume / Issue: 11 (1) Sequence Number: 6742 Start / End Page: 1 - 12 Identifier: ISSN: 2045-2322
CoNE: https://pure.mpg.de/cone/journals/resource/2045-2322