title: A review of molecular genetic studies of neurocognitive deficits in schizophrenia.
abstract: Schizophrenia is a complex and debilitating illness with strong genetic loading. In line with its heterogeneous symptomatology, evidence suggests genetic etiologies for the phenotypes in schizophrenia. A search across endophenotypes has pointed towards consistent findings in its neurocognitive deficits. Extensive literature has demonstrated impaired cognition including executive function, attention, and memory in schizophrenia patients when compared to healthy subjects. This review (1) provides an overview of recent studies and (2) develops an up-to-date conceptualization of genetic variations influencing neurocognitive functions in schizophrenia patients. Several neurotransmitter system genes have been examined given knowledge of their role in brain functions and their reported genetic associations with schizophrenia and cognition. Several genetic variations have emerged as having preliminary effects on neurocognitive deficits in schizophrenia. These include genes in the neurotrophic, serotonin, cell adhesion, and sodium channel systems. Limited evidence also suggests the dopaminergic system genes, with the most studied catechol-o-methytransferase (COMT) gene showing inconsistent findings. Further investigations with larger samples and replications are required to elucidate genetic risk for cognitive deficits in schizophrenia.
authors.affiliation: Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, Canada; Department of Psychiatry and Institute of Medical Science, University of Toronto, Toronto, Canada; MRC/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK; Department of Psychiatry, University of Cambridge, Cambridge, UK. Electronic address: gwyneth.zai@camh.ca.
authors.forename: Gwyneth
authors.initials: G
authors.lastname: Zai
authors.affiliation: MRC/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK; Department of Psychology, University of Cambridge, Cambridge, UK.
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Robbins
authors.affiliation: MRC/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK; Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Sahakian
authors.affiliation: Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, Canada; Department of Psychiatry and Institute of Medical Science, University of Toronto, Toronto, Canada.
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
mesh_terms: D003071:Cognition; D003072:Cognition Disorders; D058068:Endophenotypes; D056344:Executive Function; D006801:Humans; D012559:Schizophrenia / Q000235:genetics*
keywords: Candidate gene studies; Cognitive deficits; Genetics; Genome-wide association studies (GWASs); Neurocognition; Schizophrenia