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Cognitive Characterization of Schizophrenia Risk Variants Involved in Synaptic Transmission: Evidence of CACNA1C's Role in Working Memory

Overview of attention for article published in Neuropsychopharmacology, June 2017
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  • Good Attention Score compared to outputs of the same age (69th percentile)

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Title
Cognitive Characterization of Schizophrenia Risk Variants Involved in Synaptic Transmission: Evidence of CACNA1C's Role in Working Memory
Published in
Neuropsychopharmacology, June 2017
DOI 10.1038/npp.2017.123
Pubmed ID
Authors

Donna Cosgrove, Omar Mothersill, Kimberley Kendall, Bettina Konte, Denise Harold, Ina Giegling, Annette Hartmann, Alex Richards, Kiran Mantripragada, Michael J Owen, Michael C O’Donovan, Michael Gill, Dan Rujescu, James Walters, Aiden Corvin, Derek W Morris, Gary Donohoe

Abstract

With >100 common variants associated with schizophrenia risk, establishing their biological significance is a priority. We sought to establish cognitive effects of risk variants at loci implicated in synaptic transmission by (1) identifying GWAS schizophrenia variants whose associated gene function is related to synaptic transmission, and (2) testing for association between these and measures of neurocognitive function. We selected variants, reported in the largest GWAS to date, associated with genes involved in synaptic transmission. Associations between genotype and cognitive test score were analyzed in a discovery sample (988 Irish participants, including 798 with psychosis), and replication samples (528 UK patients with schizophrenia/schizoaffective disorder; 921 German participants including 362 patients with schizophrenia). Three loci showed significant associations with neuropsychological performance in the discovery samples. This included an association between the rs2007044 (risk allele G) within CACNA1C and poorer working memory performance (increased errors-B [95% CI]=0.635-4.535, p=0.012), an effect driven mainly by the psychosis groups. In an fMRI analysis of working memory performance (n=84 healthy participants, a subset of the discovery sample), we further found evidence that the same CACNA1C allele was associated with decreased functional connectivity between the right dorsolateral prefrontal cortex and right superior occipital gyrus/cuneus and anterior cingulate cortex. In conclusion, these data provide evidence to suggest that the CACNA1C risk variant rs2007044 is associated with poorer memory function that may result from risk carriers' difficulty with top down initiated responses caused by dysconnectivity between the right DLPFC and several cortical regions.Neuropsychopharmacology accepted article preview online, 13 June 2017. doi:10.1038/npp.2017.123.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 64 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 64 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 16%
Researcher 8 13%
Student > Bachelor 7 11%
Student > Master 7 11%
Student > Doctoral Student 4 6%
Other 8 13%
Unknown 20 31%
Readers by discipline Count As %
Neuroscience 12 19%
Psychology 9 14%
Agricultural and Biological Sciences 8 13%
Biochemistry, Genetics and Molecular Biology 3 5%
Engineering 2 3%
Other 8 13%
Unknown 22 34%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 December 2018.
All research outputs
#6,099,722
of 22,981,247 outputs
Outputs from Neuropsychopharmacology
#2,339
of 4,121 outputs
Outputs of similar age
#97,261
of 317,529 outputs
Outputs of similar age from Neuropsychopharmacology
#51
of 71 outputs
Altmetric has tracked 22,981,247 research outputs across all sources so far. This one has received more attention than most of these and is in the 73rd percentile.
So far Altmetric has tracked 4,121 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 19.2. This one is in the 42nd percentile – i.e., 42% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 317,529 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 69% of its contemporaries.
We're also able to compare this research output to 71 others from the same source and published within six weeks on either side of this one. This one is in the 26th percentile – i.e., 26% of its contemporaries scored the same or lower than it.