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Neurocognitive and neuroanatomical endophenotypes for schizophrenia: A twin and family study.

Owens, SF; (2011) Neurocognitive and neuroanatomical endophenotypes for schizophrenia: A twin and family study. Doctoral thesis , Kings College London.

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Abstract

Much research has been directed at identifying endophenotypes for schizophrenia in order to understand the factors underlying the pathogenesis of the disorder and to identify susceptibility genes. This thesis describes my work which sought to systematically investigate whether neuropsychological deficits and prefrontal cortex grey matter volume reductions are valid endophenotypes for schizophrenia, specifically investigating their heritability and genetic overlap with the disorder. I used a twin and family design, and both traditional and advanced statistical methods to address the research questions. Participants from the Maudsley Family and Maudsley Twin Studies of Schizophrenia completed clinical and neuropsychological assessments and a structural MRI scan. Four prefrontal cortex grey matter volume regions of interest (ROIs) were manually measured. The twin sample (n=469) consisted of 75 monozygotic (MZ) pairs concordant and 39 MZ pairs discordant for schizophrenia or schizoaffective disorder, 40 dizygotic (DZ) discordant pairs, and also 178 MZ and 118 DZ unaffected control twins. The family sample (n=510) consisted of 117 families this included 125 persons diagnosed with schizophrenia or schizoaffective disorder, 233 of their first and second degree relatives and 125 unaffected singleton controls. Studies one and two investigated the cognitive endophenotypes of executive functioning and episodic memory respectively, examining their heritability and whether their covariance with schizophrenia is due to shared genes or shared environment. Study three investigated the genetic and environmental sources of covariation between each prefrontal cortex ROI. It also investigated whether prefrontal ROIs are valid endophenotypes, by investigating their heritability and the source (genetic and/or environmental) of any covariation with the disorder. My results indicate that neurocognitive endophenotypes are valid endophenotypes, as they are moderately heritable and importantly share a substantial genetic overlap with the disorder. Prefrontal cortex ROIs are less heritable and also not genetically associated with schizophrenia. The identification of these neurocognitive endophenotypes will assist in understanding pathophysiology of the disorder and support their use as quantitative phenotypes in molecular genetic studies to help identify susceptibility genes.

Type: Thesis (Doctoral)
Title: Neurocognitive and neuroanatomical endophenotypes for schizophrenia: A twin and family study.
Event: Kings College London
Keywords: schizophrenia, twin, family, psychosis, neuropsychology, neurocognition, frontal lobe, executive funtion, memory
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/1410107
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