Browsing Doctoral Degrees (Psychiatry) by browse.metadata.advisor "Du Plessis, Stefan S."
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- ItemMetabolic syndrome risk factor associations with clinical, functional and cognitive outcomes during the first year of treatment in schizophrenia spectrum disorders(Stellenbosch : Stellenbosch University, 2021-03) Luckhoff, Hilmar Klaus; Emsley, Robin; Du Plessis, Stefan S.; Kilian, Sanja; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Psychiatry.ENGLISH SUMMARY : Treatment-emergent metabolic syndrome is an established risk factor for cardiovascular disease known to be associated with cognitive impairment, poor functioning and decreased quality of life in schizophrenia spectrum disorders. However, weight gain and increased lipids have also been correlated with clinical improvement in chronic schizophrenia patients. While most studies investigating the relationships between body mass and treatment outcome were conducted in patients treated with clozapine and olanzapine, it remains unclear to what extent the role of weight gain as a predictor of favourable clinical outcomes extends to include illness-specific symptom domains in first-episode patients treated with other antipsychotics with a lower obesogenic potential. The effects of other clinical (e.g. sex, substance use, baseline body mass) and treatment-related (e.g. antipsychotic dose, medication adherence) confounders on the above relationships is also unclear. In response to these knowledge gaps, the overarching aim of our doctoral studies was to explore the temporal evolution of metabolic syndrome risk factors and their effects on clinical outcome over 12 months of treatment in first-episode schizophrenia spectrum disorder patients. We found that an increase in body mass correlates with global psychopathology improvement as well as the disorganized symptoms domain of schizophrenia in first-episode patients (n=106) over 12 months of treatment, independent of the degree of antipsychotic exposure (sub-study I). The association between weight gain and clinical improvement extended to include better overall end-point cognition after 12 months of treatment in our first-episode patient cohort (n=72) (sub-study II). A differential effect for lower baseline body mass index as a predictor of end-point working memory performance was evident in substance users (unfavourable) compared to their non-using counterparts (favourable). The adverse role of low body mass index as an unfavourable prognostic marker was further substantiated by its associations with an earlier age of psychosis onset and more severe negative symptoms in first-episode patients (n=69) (sub-study III). The inclusion of a diffusion tensor imaging component to our research also revealed a similar differential association of body mass index with fronto-limbic white matter fractional anisotropy (FA) in first-episode patients (low body mass index, low FA) versus healthy controls (high body mass index, low FA) adjusting for age and sex (sub-study III). Extension of our structural neuroimaging research to include brain structures involved in the physiological, hedonic and cognitive control as part of a “core eating network” further identified smaller anterior hippocampal volumes as a sex-specific predictor of weight gain in first-episode patients (n=90) (sub-study IV). Our research supports the role of weight gain as a predictor of favourable clinical outcomes in first-episode schizophrenia patients for whom treatment adherence is assured. In contrast, low body mass and by extension failure to gain weight could represent an unfavourable prognostic marker in first-episode patients, particularly those who use substance users. Future studies would do well to combine clinical, biological and neuroimaging data in order to characterize intrinsic metabolic profiles in relation to long-term treatment outcomes in firstepisode schizophrenia.