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Schizophrenia copy number variants and associative learning

Clifton, Nicholas, Pocklington, Andrew, Scholz, B., Rees, Elliott, Walters, James, Kirov, George, O'Donovan, Michael, Owen, Michael, Wilkinson, Lawrence, Thomas, Kerrie and Hall, Jeremy 2017. Schizophrenia copy number variants and associative learning. Molecular Psychiatry 22 (2) , pp. 178-182. 10.1038/mp.2016.227

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Abstract

Large-scale genomic studies have made major progress in identifying genetic risk variants for schizophrenia. A key finding from these studies is that there is an increased burden of genomic copy number variants (CNVs) in schizophrenia cases compared with controls. The mechanism through which these CNVs confer risk for the symptoms of schizophrenia, however, remains unclear. One possibility is that schizophrenia risk CNVs impact basic associative learning processes, abnormalities of which have long been associated with the disorder. To investigate whether genes in schizophrenia CNVs impact on specific phases of associative learning we combined human genetics with experimental gene expression studies in animals. In a sample of 11 917 schizophrenia cases and 16 416 controls, we investigated whether CNVs from patients with schizophrenia are enriched for genes expressed during the consolidation, retrieval or extinction of associative memories. We show that CNVs from cases are enriched for genes expressed during fear extinction in the hippocampus, but not genes expressed following consolidation or retrieval. These results suggest that CNVs act to impair inhibitory learning in schizophrenia, potentially contributing to the development of core symptoms of the disorder.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
Psychology
Subjects: R Medicine > R Medicine (General)
Publisher: Nature Publishing Group
ISSN: 1359-4184
Funders: Wellcome Trust
Date of First Compliant Deposit: 13 January 2017
Date of Acceptance: 11 October 2016
Last Modified: 26 Dec 2018 21:51
URI: http://orca.cf.ac.uk/id/eprint/96413

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