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Abstract
There is evidence to suggest that the distinct psychotic symptoms of schizophrenia emerge because of reduced connectivity between frontal and temporal brain regions. According to theory, this reduced connectivity leads to insufficient suppression of temporal lobe structures during self-generated mentation and actions, which causes the resulting sensations to be misperceived as externally generated. Psychotic-like experiences have been argued to exist on a continuum throughout the population such that non-clinical individuals can experience low to intermediate levels of psychotic-like experiences. According to this concept –commonly referred to as ‘schizotypy’ – people suffering from schizophrenia simply represent the extreme end of this continuum. This thesis has four primary aims: 1.) To use electroencephalography (EEG) to investigate whether non-clinical individuals who score highly on schizotypy show the same electrophysiological suppression abnormalities as have repeatedly been observed in schizophrenia patients, and thereby provide empirical support for the concept of a neurophysiological continuum of psychosis. 2.) To use Diffusion Tensor Imaging (DTI) to investigate whether sensory suppression deficits in patients with schizophrenia are due to loss of white matter coherence in fiber bundles connecting frontal and temporal brain regions. 3.) To identify the relationship between white matter abnormalities in schizophrenia and psychotic symptoms such as auditory verbal hallucinations and delusions in patients with schizophrenia. 4.) To use free-water imaging to differentiate actual white matter degeneration from extracellular processes (such as neuroinflammation) in patients with schizophrenia. This research is crucially important, as understanding and elucidating the underlying causes of the characteristic symptoms of schizophrenia is a necessary first step for the development of more effective treatments.
The results from the EEG studies (chapters 2 and 3) suggest that non-clinical, highly schizotypal individuals exhibit subnormal levels of N1-suppression to self-generated speech and undelayed, button-press-elicited sounds, which can be ameliorated by imposing a sub-second delay between the button-press and the sound. To the extent that these findings are similar to the N1-suppression abnormalities which have previously been reported in patients with schizophrenia they provide empirical support for the existence of a neurophysiological ‘continuum of psychosis’. Findings from the DTI studies (chapters 4 to 6) provide evidence for a relationship between structural integrity loss and psychotic symptoms in schizophrenia and indicate that active psychotic states may be associated with neuroinflammation. Additionally, the results of the DTI studies suggest that actual white matter degeneration, independent of extracellular processes, in chronic schizophrenia might be more localized than suggested in previous studies.
Taken together, the findings from this thesis indicate that N1-suppression may represent a potential biomarker for psychosis proneness while neuroinflammation may represent a biomarker for psychosis onset. The implications of these results with respect to developing prophylactic treatments for psychosis transition are discussed.