Analysis of oligodendrocyte and myelination related genes in schizophrenia

Peirce, Timothy Rowan. 2006. Analysis of oligodendrocyte and myelination related genes in schizophrenia. PhD Thesis, Cardiff University.

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Abstract

Schizophrenia is a severe psychiatric disorder with a lifetime risk of about 1%. It affects almost all domains of mental function, including perception, emotion, cognition and social performance. Evidence from family, twin and adoption studies has shown the disorder to have a high genetic component. The aetiology of schizophrenia remains obscure but over the last decade there has been increasing evidence that abnormal oligodendrocyte function and/or myelination might play a part. The main strands of evidence that provide support for this hypothesis have been compiled from neuropathological studies, brain imaging, symptom overlap with demyelinating diseases, age related changes in myelin and evidence from micro-array studies. In this thesis, I investigated several genes of importance to oligodendrocyte function and/or myelination as candidate genes for influencing susceptibility to schizophrenia. Genes were primarily selected for study based upon their reports of altered expression in micro-array studies of post-mortem schizophrenic brain. In many cases, their potential involvement was supported by positional evidence from linkage studies and a putative functional role in the neurobiology of schizophrenia. In total thirteen genes were studied: CNP, NOGO, NgR, OMG, NGFR, GFAP, MOG, SOX 10 and APOL 1-5. During my studies I detected, modest evidence for association with three genes (CNP, NOGO and MOG). I also showed that the expression of these genes is under the influence of cis-acting polymorphisms. Whilst, the results for these genes are modest and require independent replication, they do provide some support for the general hypothesis that oligodendrocyte and/or myelination abnormalities play a role in schizophrenia aetiology.

Item Type:	Thesis (PhD)
Status:	Unpublished
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
ISBN:	9781303207785
Date of First Compliant Deposit:	30 March 2016
Last Modified:	19 Mar 2016 23:33
URI:	https://orca.cardiff.ac.uk/id/eprint/56139

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