The NOS1 variant rs6490121 is associated with variation in prefrontal function and grey matter density in healthy individuals.
Neuroimage
; 60(1): 614-22, 2012 Mar.
Article
em En
| MEDLINE
| ID: mdl-22227051
ABSTRACT
A common polymorphism within the nitric oxide sythanse-1 (NOS1) gene (rs6490121), initially identified as risk variant for schizophrenia, has been associated with variation in working memory and IQ. Here we investigated how this variation might be mediated at the level of brain structure and function. In healthy individuals (N=157), voxel based morphometry was used to compare grey matter (GM) volume between homozygous and heterozygous carriers of the 'G' allele (i.e. the allele associated with impaired cognition and schizophrenia risk) and homozygous carriers of the non-risk 'A' allele. Functional brain imaging data were also acquired from 48 participants during performance of a spatial working memory (SWM) task, and analysed to determine any effect of NOS1 risk status. An a priori region-of-interest analysis identified a significant reduction in ventromedial prefrontal GM volume in 'G' allele carriers. Risk carriers also exhibited altered patterns of activation in the prefrontal cortex, caudate, and superior parietal lobe, which were characteristic of abnormal increases in activation in frontoparietal working memory networks and a failure to disengage regions of the default mode network. These functional changes suggest a NOS1-mediated processing inefficiency, which may contribute to cognitive dysfunction in schizophrenia. While the mechanisms by which NOS1 may influence brain structure and/or function have not yet been well delineated, these data provide further evidence for a role of NOS1 in risk for schizophrenia via an impact upon cognitive function.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
/
Óxido Nítrico Sintase Tipo I
/
Memória de Curto Prazo
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Neuroimage
Assunto da revista:
DIAGNOSTICO POR IMAGEM
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Irlanda