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Title: Neuropsychological assessment and functional magnetic resonance imaging of verbal declarative memory performance in relatives of schizophrenia patients and controls
Author: Whyte, Marie-Claire
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2005
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The Edinburgh High Risk Study recruited 162 young adults with at least one first or second degree relative with schizophrenia and 43 closely matched controls. A broad neuropsychological (NP) and clinical assessment battery was administered every 18-24 months over 10 years, while participants underwent between 1 and 3 functional magnetic resonance imaging (fMRI) scans during a verbal memory and executive function task over 5 years. Methods: Baseline predictors of schizophrenia, performance changes over 2 NP assessments, and the influence of genetic liability were examined in high risk participants with (HR+) and without psychotic symptoms (HR-), those who are now ill (Scz) and controls (C ), using one-way ANOVAs and repeated measures ANCOVAs. Aspects of verbal and non-verbal memory were also compared between the HR and C in the first 100 participants to undergo an fMRI scan using one-way ANOVAs. In the same participants, differences between groups in blood oxygen level dependent (BOLD) fMRI brain responses during an event related verbal encoding (word classification) and retrieval task were investigated using fixed and random effects general linear models. Results: On a test of verbal learning at baseline, Scz performed significantly less well than HR. However, there were no significant interactions of time by group, and HR showed stable impairments relative to C on immediate and delayed prose recall, delayed list recall and response suppression across both assessments before and after controlling for IQ. Measures of genetic liability were inversely correlated with delayed prose recall over time. HR showed poorer cued delayed recall, and less word retention between short and long delay recall trials on a verbal learning test. A visual recognition test also significantly discriminated between HR and C. Behavioural analysis of the fMRI verbal memory task revealed no differences between groups in reaction time or accuracy. However, during encoding there was a greater BOLD response in the right inferior frontal lobe (BA45/44) in HR relative to C, and in the right inferior parietal lobule (BA7/40) in HR+ relative to C and HR-. During correct recognition compared to correct rejection responses there was a greater bilateral cerebellar and left inferior frontal response in HR relative to C, and an increased thalamus response in HR-relative to HR+. Conclusions: Stable differences in NP performance over time suggest a trait deficit, which is relatively unaffected by the presence of psychotic symptoms and schizophrenia onset, although small numbers might be have been precluded detection significant time by group interactions. Poorer verbal memory performance overall in Scz suggests that this deficit is more pronounced in those who go on to develop schizophrenia. Non-verbal learning impairments reflect encoding deficits, while verbal learning impairments reflect encoding and retention difficulties in the HR group.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available