To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
A single nucleotide polymorphism (rs7914558) within the cyclin M2
(CNNM2) gene was recently identified as a common risk
variant for schizophrenia. The mechanism by which CNNM2
confers risk is unknown.
To determine the impact of the rs7914558 risk ‘A’ allele
on measures of neurocognition, social cognition and brain structure.
Patients with schizophrenia (n = 400) and healthy
controls (n = 160) completed measures of
neuropsychological function and social cognition. Structural magnetic
resonance imaging data were also acquired from an overlapping sample of
Irish healthy controls (n = 159) and an independent
sample of Italian patients (n = 82) and healthy controls
(n = 39).
No effects of genotype on neuropsychological test performance were
observed. However, a dosage effect of the risk allele was found for an
index of social cognition (i.e. attributional style), such that risk
status was associated with reduced self-serving bias across groups
(GG>AG>AA, P<0.05). Using voxel-based
morphometry to investigate neuroanatomical regions putatively supporting
social cognition, risk carriers had relatively increased grey matter
volume in the right temporal pole and right anterior cingulate cortex
(Pcorrected<0.05) in the Irish healthy controls sample;
neuroanatomical associations between CNNM2 and grey
matter volume in anterior cingulate cortex were also observed in the
Italian schizophrenia and healthy controls samples.
Although the biological role of CNNM2 in schizophrenia
remains unknown, these data suggest that this CNNM2 risk
variant rs7914558 may have an impact on neural systems relevant to social
cognition. How such effects may mediate the relationship between genotype
and disease risk remains to be established.
A single nucleotide polymorphism rs12807809 located upstream of the neurogranin (NRGN) gene has been identified as a risk variant for schizophrenia in recent genome-wide association studies. To date, there has been little investigation of the endophenotypic consequences of this variant, and our own investigations have suggested that the effects of this gene are not apparent at the level of cognitive function in patients or controls. Because the impact of risk variants may be more apparent at the level of brain, the aim of this investigation was to delineate whether NRGN genotype predicted variability in brain structure and/or function. Healthy individuals participated in structural (N = 140) and/or functional (N = 36) magnetic resonance imaging (s/fMRI). Voxel-based morphometry was used to compare gray and white matter volumes between carriers of the non-risk C allele (i.e., CC/CT) and those who were homozygous for the risk T allele. Functional imaging data were acquired during the performance of a spatial working memory task, and were also analyzed with respect to the difference between C carriers and T homozygotes. There was no effect of the NRGN variant rs12807809 on behavioral performance or brain structure. However, there was a main effect of genotype on brain activity during performance of the working memory task, such that while C carriers exhibited a load-independent decrease in left superior frontal gyrus/BA10, TT individuals failed to show a similar decrease in activity. The failure to disengage this ventromedial prefrontal region, despite preserved performance, may be indicative of a reduction in processing efficiency in healthy TT carriers. Although it remains to be established whether this holds true in larger samples and in patient cohorts, if valid, this suggests a potential mechanism by which NRGN variability might contribute to schizophrenia risk.
Email your librarian or administrator to recommend adding this to your organisation's collection.