NEUROCOGNITIVE IMPAIRMENT AND BRAIN VOLUME CHANGES IN THE CLINICAL HIGH-RISK STATE FOR PSYCHOSIS

Student thesis: Doctoral ThesisDoctor of Philosophy

Abstract

People at clinical high-risk for psychosis (CHR) are characterised by significant global and specific neurocognitive impairments. Moreover, these individuals present with poor social and occupational functioning and a 20% risk of developing psychosis within two years. The purpose of this thesis was first to explore the nature and longitudinal course of neurocognitive impairments in the CHR state, linking them to longer-term clinical and functional outcomes. Furthermore, while there is evidence for structural brain alterations in CHR individuals, the reliability of these alterations and their association with changes in neurocognitive functioning of CHR are currently unknown. Consequently, the second aim of this thesis was to conduct a reliability assessment of structural brain measurements and explore dynamic brain structure-neurocognition relationships in key brain regions implicated in psychosis.

Following a qualitative introductory review, the findings presented in Chapter 2 indicate that impairments in verbal memory and verbal fluency are not associated with later development of psychosis among CHR individuals but predict remission from the CHR state and improved functioning at 2-year follow-up. Using advanced meta-analytic techniques, Chapter 3 provides evidence that, although most deficits in neurocognition remain stable over time, longitudinal differences in some specific neurocognitive functioning can be observed between CHR and healthy individuals, as well as CHR individuals who later developed psychosis (CHR-T) compared to CHR who did not develop psychosis (CHR-NT). The results of Chapter 4 additionally demonstrate that the rate of change in verbal memory performance over a 2-year period differs between CHR-T and CHR-NT, and that these neurocognitive changes are associated with changes in anterior cingulate cortex and cerebellum volumes in the CHR sample. Chapter 5 provides robust evidence that structural brain measurements are highly reliable but identifies certain image processing and image acquisition factors that may adversely impact the reliability of measurements. Chapter 6 of this thesis extends the discussion of the results from Chapters 2 – 5, addressing the implications for research and the development of cognitive interventions for CHR individuals. Findings of this thesis demonstrate the importance of understanding neurocognitive impairments in the CHR state for early intervention among CHR-T individuals and for targeted cognitive intervention to improve functional outcomes of those at incipient risk for psychosis.
Date of Award1 Jul 2022
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorMatthew Kempton (Supervisor), Hannah Dickson (Supervisor) & Philip McGuire (Supervisor)

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