Browsing Doctoral Degrees (Psychiatry) by Author "Asmal, Laila"
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- ItemBrain structural and white matter changes in first-episode schizophrenia and their demographic, clinical and cognitive correlates(Stellenbosch : Stellenbosch University, 2018-03) Asmal, Laila; Emsley, Robin; Dazzan, Paola; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Psychiatry.ENGLISH SUMMARY : In schizophrenia, decreased brain volume and altered cortical thinning (especially in the frontal and temporal areas), as well as white matter deficits are described at the first-episode. The relationship between these brain measures and clinical symptoms, whether there is progression, and the extent to which antipsychotic medication contribute to or mitigate those changes remains unclear. The aim of this PhD was to examine cortical thickness, brain volume (cortical, subcortical, white matter) and diffusion tensor imaging data, looking at the relationship between these brain measures and clinical variables in the first year of schizophrenia treatment. This PhD focused on the MRI subcomponent of a larger prospective longitudinal study in first-episode schizophrenia (FES) patients treated with flupenthixol decanoate medication. The thesis integrates the findings of five journal manuscripts that each focused on a clinically relevant neuroimaging question that emerged as we assessed patients in the parent study, namely insight, childhood trauma, neuroimaging predictors of symptom expression, and antipsychotic related brain changes. In our first manuscript, baseline fractional anisotropy (FA) in a number of white matter tracts predicted poorer total insight in 89 FES patients, with a predilection for tracts associated with cortical midline structures. In our second manuscript, the ‘symptom misattribution’ domain of clinical insight was associated with significantly thinner left anterior cingulate and left rostral middle frontal cortices. Our studies address a need for research in larger samples in FES to better understand the neurobiology of insight in schizophrenia. In our third manuscript, baseline FA deficits in cortico-limbic circuitry was associated with childhood trauma in 53 FES patients compared to 51 controls, and there were differential effects of childhood emotional neglect (increased FA) and sexual abuse (decreased FA) on white matter in patients. To our knowledge, at the time of manuscript submission for publication, this was the first study examining the relationship between childhood trauma, FA and FES. For our fourth manuscript, baseline brain measures in 54 FES patients were differentially associated with state and trait symptom expression over 12 months, with global gray matter significantly associated with sensory integration and verbal learning trait scores, cortical volume with verbal learning trait scores, cortical thickness with social and occupational functioning trait scores, and white matter volume with motor coordination state scores. Of potential relevance to patient care is that these neuroimaging deficits at initial presentation in FES may predict enduring trait deficits in cognition, functioning and neurological soft signs. For our final manuscript, total antipsychotic dose was a predictor of substantial cortical brain volume reductions over twelve months of treatment in 23 antipsychotic naïve patients compared to 53 matched controls. Our finding of a significant relationship between antipsychotic dose and cortical volume reduction in this study strongly suggests causality. Future research directions stemming from this PhD include further exploration of our longitudinal data, strengthening our clinical assessments of insight and childhood trauma, connectomic analyses, a multi-modality neuroimaging approach, hippocampal subfield segmentation, and broadening our international collaborations.