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Title: Neurobiological disease markers in drug naïve schizophrenia patients in Taiwan : a cross sectional study
Author: Chen, Kao Chin
ISNI:       0000 0004 5917 8997
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2016
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A major factor driving research into the pathophysiology of schizophrenia has been responsiveness to antipsychotic (dopamine antagonist) medication. Despite this it remains unclear whether there is a detectable disorder of dopamine function in patients who develop schizophrenia and if so, how it relates to other physiological markers of the condition. One reason why research in this area is such a challenge is the confounding effects of antipsychotic treatment. I carried out a case control study on drug-naïve patients with schizophrenia who presented to the university hospital clinic in Tainan, Taiwan. I obtained a number of clinical and neurobiological measures, thought to be possible disease biomarkers. I assessed patients before they received treatment using the following methods: (I) single photon emission computed tomography (SPECT) - [99mTc] TRODAT-1 for dopamine transporter (DAT) availability; and (II) Electro-encephalograms to test event-related potentials (ERPs). Such measures were also obtained on healthy controls and appropriate comparisons made. Clinical state was assessed using standard scales. (I): DAT availability through [99mTc]-TRODAT-1 SPECT was compared between 47 drug naïve patients with recent onset schizophrenia and 112 healthy controls. I also conducted a random effects meta-analysis of the available literature synthesizing the results of six comparable published papers as well as my current data. The mean specific striatal binding ratio showed a trend for a reduction among the patients compared with controls (estimated difference = 0.071; 95% CI 20.01, 0.15; P =.08). There was an effect of sex, whereby females had a higher ratio of specific striatal binding than males. Age was negatively correlated with the ratio of specific striatal binding, both in patients and controls. The meta-analysis provided a pooled standardized effect size (Cohen’s d) of -0.07 (95% CI: -0.31, 0.18; p= 0.60) for the patient versus control comparison in TRODAT binding, with no evidence of heterogeneity between studies or publication bias. The findings suggest that striatal dopamine transporter levels are not altered in the early stages of schizophrenia before medication is introduced. (II): ERP differences were explored between 36 drug naïve patients with schizophrenia and 138 healthy controls and P300 performance was examined in relation to dopamine transporter (DAT) availability. I also conducted a random-effects meta-analysis of the available literature synthesizing the results of 3 comparable published articles on drug naïve patients as well as my local study. The mean P300 ERP showed no overall significant difference between patients and controls in latency or in amplitude. However, there was an increase in P300 latency with age which was more pronounced in the patient group. No effects of DAT availability on P300 latency or amplitude were detected. The meta-analysis provided a latency pooled standardized effect size (Cohen’s d) of -0.13 (95% CI -0.37, 0.12; P = 0.31), and an amplitude pooled standardized effect size (Cohen’s d) of 0.48 (95% CI -0.002, 0.97; P=0.05) with patients showing a borderline significant reduction. My findings suggest the P300 ERP latency is not altered in the early stages of schizophrenia before medication is introduced, and the DAT availability does not influence the P300 ERP amplitude or latency. P300 ERP amplitude reduction could be an indicator of the progression of illness and chronicity. The importance of taking into account medication effects is emphasized by this research as is the value of converging methodologies such as research with families and other ‘at risk’ populations and longitudinal cohort studies.
Supervisor: Bramon-Bosch, Elvira ; David, Anthony Sion Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available