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An exploration of functional connectivity and GABA in schizophrenia and related conditions

Williams, Gemma 2018. An exploration of functional connectivity and GABA in schizophrenia and related conditions. PhD Thesis, Cardiff University.
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Schizophrenia is a severe and enduring mental illness with psychopathology including positive symptoms, negative symptoms and cognitive impairment. It has been hypothesised that such symptoms represent a loss of integration within and between brain regions. This is known as the dysconnectivity hypothesis and integrates with other neurochemical hypotheses of the disorder. In this thesis, I sought to explore the dysconnectivity hypothesis using amplitude envelope correlation in MEG, firstly in two groups of individuals with schizophrenia. I then sought to address the continuum model of schizophrenia through exploring functional connectivity in two groups with high schizotypy. Next, I explored dysconnectivity in schizophrenia in more depth by looking separately at individuals with recent onset psychosis and those with established schizophrenia. I then went on to look at connectivity following ketamine administration thus seeking to link this model of schizophrenia with my findings in those with schizophrenia. Finally, I explored the GABA hypothesis of schizophrenia using MRS, again in two groups of individuals with schizophrenia, at different stages of illness and linked this with connectivity. Overall, this work supports the dysconnectivity hypothesis of schizophrenia, finding reduced connectivity in schizophrenia. Such changes are found predominantly in the later stages of the disorder suggesting the possibility of progressive changes in connectivity throughout its course. I found increased connectivity following ketamine administration in the same frequency band and region suggesting the drug does not model later stages of the disorder well (where I predominantly found hypo-connectivity). In addition, I found reduced GABA iv in later stages of schizophrenia but not in early stages, again suggesting progressive changes throughout the course of the disorder. Finally, I also found hypo-connectivity in healthy volunteers with high schizotypy scores suggesting biological continuity between subclinical symptoms and diagnosable schizophrenia. Overall, these results add support to the dysconnectivity hypothesis, the GABA/glutamate hypothesis and the continuum hypothesis of schizophrenia.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Medicine
Date of First Compliant Deposit: 22 May 2019
Last Modified: 24 May 2019 11:39

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