The NOS1 variant rs6490121 is associated with variation in prefrontal function and grey matter density in healthy individuals.

Hdl Handle:
http://hdl.handle.net/10147/238791
Title:
The NOS1 variant rs6490121 is associated with variation in prefrontal function and grey matter density in healthy individuals.
Authors:
Rose, Emma J; Greene, Ciara; Kelly, Sinead; Morris, Derek W; Robertson, Ian H; Fahey, Ciara; Jacobson, Sarah; O'Doherty, John; Newell, Fiona N; McGrath, Jane; Bokde, Arun; Garavan, Hugh; Frodl, Thomas; Gill, Michael; Corvin, Aiden P; Donohoe, Gary
Affiliation:
Neuropsychiatric Genetics Research Group & Institute of Molecular Medicine, Department of Psychiatry, Trinity College Dublin, Ireland. rosee@tcd.ie
Citation:
The NOS1 variant rs6490121 is associated with variation in prefrontal function and grey matter density in healthy individuals. 2012, 60 (1):614-22 Neuroimage
Journal:
NeuroImage
Issue Date:
Mar-2012
URI:
http://hdl.handle.net/10147/238791
DOI:
10.1016/j.neuroimage.2011.12.054
PubMed ID:
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.
Item Type:
Article
Language:
en
MeSH:
Adult; Brain; Female; Humans; Magnetic Resonance Imaging; Male; Memory, Short-Term; Nitric Oxide Synthase Type I; Organ Size; Prefrontal Cortex; Young Adult
ISSN:
1095-9572

Full metadata record

DC FieldValue Language
dc.contributor.authorRose, Emma Jen_GB
dc.contributor.authorGreene, Ciaraen_GB
dc.contributor.authorKelly, Sineaden_GB
dc.contributor.authorMorris, Derek Wen_GB
dc.contributor.authorRobertson, Ian Hen_GB
dc.contributor.authorFahey, Ciaraen_GB
dc.contributor.authorJacobson, Sarahen_GB
dc.contributor.authorO'Doherty, Johnen_GB
dc.contributor.authorNewell, Fiona Nen_GB
dc.contributor.authorMcGrath, Janeen_GB
dc.contributor.authorBokde, Arunen_GB
dc.contributor.authorGaravan, Hughen_GB
dc.contributor.authorFrodl, Thomasen_GB
dc.contributor.authorGill, Michaelen_GB
dc.contributor.authorCorvin, Aiden Pen_GB
dc.contributor.authorDonohoe, Garyen_GB
dc.date.accessioned2012-08-15T14:01:50Z-
dc.date.available2012-08-15T14:01:50Z-
dc.date.issued2012-03-
dc.identifier.citationThe NOS1 variant rs6490121 is associated with variation in prefrontal function and grey matter density in healthy individuals. 2012, 60 (1):614-22 Neuroimageen_GB
dc.identifier.issn1095-9572-
dc.identifier.pmid22227051-
dc.identifier.doi10.1016/j.neuroimage.2011.12.054-
dc.identifier.urihttp://hdl.handle.net/10147/238791-
dc.description.abstractA 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.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to NeuroImageen_GB
dc.subject.meshAdult-
dc.subject.meshBrain-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshMagnetic Resonance Imaging-
dc.subject.meshMale-
dc.subject.meshMemory, Short-Term-
dc.subject.meshNitric Oxide Synthase Type I-
dc.subject.meshOrgan Size-
dc.subject.meshPrefrontal Cortex-
dc.subject.meshYoung Adult-
dc.titleThe NOS1 variant rs6490121 is associated with variation in prefrontal function and grey matter density in healthy individuals.en_GB
dc.typeArticleen
dc.contributor.departmentNeuropsychiatric Genetics Research Group & Institute of Molecular Medicine, Department of Psychiatry, Trinity College Dublin, Ireland. rosee@tcd.ieen_GB
dc.identifier.journalNeuroImageen_GB
dc.description.provinceLeinsteren

Related articles on PubMed

All Items in Lenus, The Irish Health Repository are protected by copyright, with all rights reserved, unless otherwise indicated.