title: Schizophrenia copy number variants and associative learning.
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.
authors.affiliation: Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK.
authors.forename: N E
authors.initials: NE
authors.lastname: Clifton
authors.affiliation: Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK.|MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Pocklington
authors.affiliation: Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK.
authors.forename: B
authors.initials: B
authors.lastname: Scholz
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
authors.forename: E
authors.initials: E
authors.lastname: Rees
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
authors.forename: J T R
authors.initials: JT
authors.lastname: Walters
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
authors.forename: G
authors.initials: G
authors.lastname: Kirov
authors.affiliation: Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK.|MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
authors.forename: M C
authors.initials: MC
authors.lastname: O'Donovan
authors.affiliation: Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK.|MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Owen
authors.affiliation: Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK.|MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.|School of Psychology, Cardiff University, Cardiff, UK.
authors.forename: L S
authors.initials: LS
authors.lastname: Wilkinson
authors.affiliation: Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK.|School of Biosciences, Cardiff University, Cardiff, UK.
authors.forename: K L
authors.initials: KL
authors.lastname: Thomas
authors.affiliation: Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK.|MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
authors.forename: J
authors.initials: J
authors.lastname: Hall
mesh_terms: D000818:Animals; D001245:Association Learning / Q000502:physiology*; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000502:physiology; D016022:Case-Control Studies; D003214:Conditioning, Classical; D056915:DNA Copy Number Variations / Q000235:genetics*; D016208:Databases, Factual; D005239:Fear / Q000502:physiology / Q000523:psychology; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D051381:Rats; D012559:Schizophrenia / Q000235:genetics*