Age-modulated association between prefrontal NAA and the BDNF gene

Salehi, Basira; Preuss, Nora; van der Veen, Jan Willem; Shen, Jun; Neumeister, Alexander; Drevets, Wayne C; Hodgkinson, Colin; Goldman, David; Wendland, Jens R; Singleton, Andrew; Gibbs, Jesse R; Cookson, Mark R; Hasler, Gregor (2013). Age-modulated association between prefrontal NAA and the BDNF gene. International journal of neuropsychopharmacology, 16(6), pp. 1185-1193. Cambridge: Cambridge University Press 10.1017/S1461145712001204

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Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of psychiatric and neurological disorders and in the mechanisms of antidepressant pharmacotherapy. Psychiatric and neurological conditions have also been associated with reduced brain levels of N-acetyl-aspartate (NAA), which has been used as a putative marker of neural integrity. However, few studies have explored the relationship between BDNF polymorphisms and NAA levels directly. Here, we present data from a single-voxel proton magnetic resonance spectroscopy study of 64 individuals and explore the relationship between BDNF polymorphisms and prefrontal NAA level. Our results indicate an association between a single nucleotide polymorphism (SNP) within BDNF, known as rs1519480, and reduced NAA level (p = 0.023). NAA levels were further predicted by age and Asian ancestry. There was a significant rs1519480 × age interaction on NAA level (p = 0.031). Specifically, the effect of rs1519480 on NAA level became significant at age ⩾34.17 yr. NAA level decreased with advancing age for genotype TT (p = 0.001) but not for genotype CT (p = 0.82) or CC (p = 0.34). Additional in silico analysis of 142 post-mortem brain samples revealed an association between the same SNP and reduced BDNF mRNA expression in the prefrontal cortex. The rs1519480 SNP influences BDNF mRNA expression and has an impact on prefrontal NAA level over time. This genetic mechanism may contribute to inter-individual variation in cognitive performance seen during normal ageing, as well as contributing to the risk for developing psychiatric and neurological conditions.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > University Psychiatric Services > University Hospital of Psychiatry and Psychotherapy > Healthcare Research 07 Faculty of Human Sciences > Institute of Psychology > Cognitive Psychology, Perception and Methodology
UniBE Contributor:	Salehi, Basira, Preuss, Nora, Hasler, Gregor
Subjects:	100 Philosophy > 150 Psychology 600 Technology > 610 Medicine & health
ISSN:	1461-1457
Publisher:	Cambridge University Press
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:39
Last Modified:	05 Dec 2022 14:12
Publisher DOI:	10.1017/S1461145712001204
PubMed ID:	23253771
Web of Science ID:	000319973200001
URI:	https://boris.unibe.ch/id/eprint/15770 (FactScience: 223213)