Multimodal markers of emerging and early-stage psychosis

Brunner, Gina (2024) Multimodal markers of emerging and early-stage psychosis. PhD thesis, University of Glasgow.

Abstract

Psychotic disorders such as schizophrenia are a family of severe psychiatric conditions which have been associated with substantial disease burden for patients, caregivers, and healthcare systems. Psychotic disorders are typically preceded by a prodromal phase, where psychotic symptoms are present but below the diagnostic threshold. The clinical at-risk state for psychosis can detect this state, but not all individuals who meet criteria for the at-risk state will ultimately develop psychosis. Being able to accurately predict clinical trajectories could help clinicians assign the most appropriate treatments to patients at the earliest signs of illness, thus reducing the risk of future distress and disability of patients. However, it is not yet known exactly which alterations characterise psychosis risk.

Identifying markers of emerging and early-stage psychosis is therefore an important step in the prediction of clinical outcomes. This work aims at identifying markers of psychosis from multiple data modalities, from behavioural to neuroanatomical and functional neurological features. It shows an association between cognitive function and global functioning, and implicates an important role for the hippocampus and the brain networks it is embedded in as markers of early-stage psychosis. Furthermore, another candidate marker thought to explain alterations to the ventricular system, the choroid plexus, is rejected.

Altogether, the results indicate that functional outcomes in individuals at clinical high-risk for psychosis are predicted by cognition, but are also relatively stable over time. Here, cognitive deficits are associated with psychosis risk, whereas individuals with other psychiatric problems who do not meet clinical high-risk for psychosis criteria do not show the same impairments. In the neuroanatomical domain, hippocampal volumes are decreased in early psychosis, but not in individuals with other psychiatric problems, thus indicating specificity to psychosis. While changes to the hippocampal surface are more regionally confined in clinical high-risk states for psychosis, the majority of the surface shows contraction in first-episode psychosis. The choroid plexus, however, is not associated with either psychosis risk, or early-stage psychosis and chronic schizophrenia. Again highlighting a key role for the hippocampus, functional neuroimaging shows that connectivity between the frontal cortex and hippocampus is lower in early-stage psychosis, while the overall role of the hippocampus in the network differs between illness stages. No such effects are seen for the clinical control group.

While the identified cognitive, neuroanatomical and functional neuroimaging markers appear to be specific to psychosis in the studied sample, they do not predict clinical outcomes particularly in clinical high-risk markers for psychosis. This suggests that the contributions of each data modality are unique, meaning that the results from this thesis could be used to plan future studies in which multimodal prediction models using these markers may be explored.

• Item Type: Thesis (PhD)
• Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Supervisor's Name: Fracasso, Dr. Alessio and Uhlhaas, Professor Peter
• Date of Award: 2024
• Depositing User: Theses Team
• Unique ID: glathesis:2024-84567
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 18 Sep 2024 08:50
• Last Modified: 18 Sep 2024 08:53
• Thesis DOI: 10.5525/gla.thesis.84567
• URI: https://theses.gla.ac.uk/id/eprint/84567

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