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Cognition, psychopathology and the role of genetic variation in Catechol-O-Methyltransferase in children at increased risk of schizophrenia

Niarchou, Maria 2013. Cognition, psychopathology and the role of genetic variation in Catechol-O-Methyltransferase in children at increased risk of schizophrenia. PhD Thesis, Cardiff University.
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In this thesis I explored cognition, psychopathology and the role of Catechol-O-Methyltransferase (COMT) in children at increased risk of schizophrenia with the aim of making a contribution to our understanding of the processes that take place early in the development of psychosis. Two samples were studied. The first sample came from the population-based Avon Longitudinal Study of Parents and Children (ALSPAC) where I examined the relationships between a priori selected cognitive domains and psychotic experiences (PEs). The results indicated that impaired processing speed and attention were related to greater risk of PEs in children, with processing speed being a key cognitive feature. Moreover, the relationships between cognition and later occurrence of PEs were similar to those that have previously been reported between cognition and schizophrenia. I also examined whether genetic variation in COMT was associated with PEs indirectly through cognition and anxiety disorders. The findings showed that COMT was indirectly associated with PEs through processing speed, IQ and attention. The second sample comprised children with 22q11.2 Deletion Syndrome (22q11.2DS). I examined the nature and prevalence of psychopathology and cognitive dysfunction in the sample and their siblings and to what extent the children’s intellectual impairment indirectly influences the risk of psychopathology associated with the deletion. There were high rates of psychopathology and cognitive impairments in children with 22q11.2DS. However, I found no evidence for an indirect association between the deletion and the risk of psychopathology through cognition. Finally, there was no evidence that COMT is related to the susceptibility of children with 22q11.2DS to cognitive and psychiatric problems. These findings have potentially important implications for our understanding of the development of psychosis during childhood and they also show that using different research designs to investigate specific aims in samples at increased risk enables the researcher to widen their scope of interpretation.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Date of First Compliant Deposit: 30 March 2016
Last Modified: 20 Feb 2018 14:21

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