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

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...

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Autores principales:	Louise Martens, Luisa Herrmann, Lejla Colic, Meng Li, Anni Richter, Gusalija Behnisch, Oliver Stork, Constanze Seidenbecher, Björn H. Schott, Martin Walter
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c991328982f64c80be18ec357d3b7d82
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spelling	oai:doaj.org-article:c991328982f64c80be18ec357d3b7d822021-12-02T11:45:01ZMet carriers of the BDNF Val66Met polymorphism show reduced Glx/NAA in the pregenual ACC in two independent cohorts10.1038/s41598-021-86220-32045-2322https://doaj.org/article/c991328982f64c80be18ec357d3b7d822021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86220-3https://doaj.org/toc/2045-2322Abstract 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.Louise MartensLuisa HerrmannLejla ColicMeng LiAnni RichterGusalija BehnischOliver StorkConstanze SeidenbecherBjörn H. SchottMartin WalterNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Louise Martens Luisa Herrmann Lejla Colic Meng Li Anni Richter Gusalija Behnisch Oliver Stork Constanze Seidenbecher Björn H. Schott Martin Walter Met carriers of the BDNF Val66Met polymorphism show reduced Glx/NAA in the pregenual ACC in two independent cohorts
description	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.
format	article
author	Louise Martens Luisa Herrmann Lejla Colic Meng Li Anni Richter Gusalija Behnisch Oliver Stork Constanze Seidenbecher Björn H. Schott Martin Walter
author_facet	Louise Martens Luisa Herrmann Lejla Colic Meng Li Anni Richter Gusalija Behnisch Oliver Stork Constanze Seidenbecher Björn H. Schott Martin Walter
author_sort	Louise Martens
title	Met carriers of the BDNF Val66Met polymorphism show reduced Glx/NAA in the pregenual ACC in two independent cohorts
title_short	Met carriers of the BDNF Val66Met polymorphism show reduced Glx/NAA in the pregenual ACC in two independent cohorts
title_full	Met carriers of the BDNF Val66Met polymorphism show reduced Glx/NAA in the pregenual ACC in two independent cohorts
title_fullStr	Met carriers of the BDNF Val66Met polymorphism show reduced Glx/NAA in the pregenual ACC in two independent cohorts
title_full_unstemmed	Met carriers of the BDNF Val66Met polymorphism show reduced Glx/NAA in the pregenual ACC in two independent cohorts
title_sort	met carriers of the bdnf val66met polymorphism show reduced glx/naa in the pregenual acc in two independent cohorts
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c991328982f64c80be18ec357d3b7d82
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Met carriers of the BDNF Val66Met polymorphism show reduced Glx/NAA in the pregenual ACC in two independent cohorts

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