+publisher:"Stellenbosch University" +contributor:("Emsley, Robin")

Stellenbosch University

1. Chiliza, Bonginkosi. A prospective study of clinical, biological and functional aspects of outcome in first episode psychosis.

Degree: PhD, Psychiatry, 2015, Stellenbosch University

URL: http://hdl.handle.net/10019.1/97904

► ENGLISH ABSTRACT: Prospective, longitudinal clinical studies in first-episode schizophrenia have become relatively commonplace over the past two decades or more and have provided a wealth… (more)

▼ ENGLISH ABSTRACT: Prospective, longitudinal clinical studies in first-episode schizophrenia have become relatively commonplace over the past two decades or more and have provided a wealth of useful information regarding the clinical presentation, treatment, course and outcome of the illness. However, there remain several unanswered questions. The majority of the studies have been conducted in upper income countries using often costly medication with heterogeneous samples. While the overall outcome of patients showed some progress, there is room for improvement yet. The overall aim of the dissertation was to study the clinical, biological and functional aspects of outcome in first episode schizophrenia in a resource constrained setting. We conducted a prospective, non-comparative, longitudinal study over 12 months assessing the efficacy and tolerability of a cost effective, long-acting injectable antipsychotic (LAI; flupenthixol decanoate) combined with an assertive monitoring program (AMP) among first-episode schizophrenia patients. Efficacy was measured by examining rates of response, remission and relapse, as well as quality of life and social and occupational functioning. Tolerability of our intervention was assessed by measuring extrapyramidal symptoms, and weight and metabolic changes. We also examined the evolution of treatment refractoriness by studying the rates of non-response, and other associated predictor and outcome features. We found high rates of acceptance and adherence to the LAI and AMP. Seventy percent of our patients completed the 12 months of treatment. Treatment response was achieved by 82% of the participants and 60% achieved remission. Although 19% of our patients relapsed, the majority of the relapses were mild and did not require hospitalisation. Patients experienced significant quality of life and social and occupational functioning improvements. We found mild rates of extrapyramidal effects, present in only a third of our cohort. The majority of the extrapyramidal effects were treated with anticholinergics or propranolol. Only 3% of our patients developed transient dyskinesia over the duration of the study. However, our cohort gained considerable weight, with statistically significant increases in BMI (p< .0001) and waist circumference (p=0.0006). Our cohort also experienced significant deleterious changes to their lipid profiles. Of particular concern was the increase in triglycerides (p=0.03) and a significant decrease in high density lipoprotein (p=0.005) leading to a 91% increase in the triglyceride/high density lipoprotein ratio. With regards to emerging treatment refractoriness, 12% of our patients met our pre-defined criteria for non-response. Non-responders were younger and at baseline showed more prominent disorganised symptoms, poorer social and occupational functioning, poorer quality of life for psychological, social and environmental domains, more prominent neurological soft signs (NSS), and lower BMI. At endpoint the non-responders were… Advisors/Committee Members: Emsley, Robin, Stellenbosch University. Faculty of Health Sciences. Dept. of Psychiatry..

Subjects/Keywords: clinical studies, schizophrenia, injectable antipsychotic, first-episode schizophrenia patients; UCTD; Schizophrenia – Treatment

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APA (6^th Edition):

Chiliza, B. (2015). A prospective study of clinical, biological and functional aspects of outcome in first episode psychosis. (Doctoral Dissertation). Stellenbosch University. Retrieved from http://hdl.handle.net/10019.1/97904

Chicago Manual of Style (16^th Edition):

Chiliza, Bonginkosi. “A prospective study of clinical, biological and functional aspects of outcome in first episode psychosis.” 2015. Doctoral Dissertation, Stellenbosch University. Accessed January 19, 2021. http://hdl.handle.net/10019.1/97904.

MLA Handbook (7^th Edition):

Chiliza, Bonginkosi. “A prospective study of clinical, biological and functional aspects of outcome in first episode psychosis.” 2015. Web. 19 Jan 2021.

Vancouver:

Chiliza B. A prospective study of clinical, biological and functional aspects of outcome in first episode psychosis. [Internet] [Doctoral dissertation]. Stellenbosch University; 2015. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10019.1/97904.

Council of Science Editors:

Chiliza B. A prospective study of clinical, biological and functional aspects of outcome in first episode psychosis. [Doctoral Dissertation]. Stellenbosch University; 2015. Available from: http://hdl.handle.net/10019.1/97904

Stellenbosch University

2. Asmal, Laila. Brain structural and white matter changes in first-episode schizophrenia and their demographic, clinical and cognitive correlates.

Degree: PhD, Psychiatry, 2018, Stellenbosch University

URL: http://hdl.handle.net/10019.1/103286

► ENGLISH SUMMARY : In schizophrenia, decreased brain volume and altered cortical thinning (especially in the frontal and temporal areas), as well as white matter deficits… (more)

▼ 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… Advisors/Committee Members: Emsley, Robin, Dazzan, Paola, Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Psychiatry..

Subjects/Keywords: Schizophrenia – Diagnostic imaging; Schizophrenia – Neuroimaging; Brain – Diagnostic imaging; Neurosciences; Diffusion tensor imaging; White matter; UCTD

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Asmal, L. (2018). Brain structural and white matter changes in first-episode schizophrenia and their demographic, clinical and cognitive correlates. (Doctoral Dissertation). Stellenbosch University. Retrieved from http://hdl.handle.net/10019.1/103286

Chicago Manual of Style (16^th Edition):

Asmal, Laila. “Brain structural and white matter changes in first-episode schizophrenia and their demographic, clinical and cognitive correlates.” 2018. Doctoral Dissertation, Stellenbosch University. Accessed January 19, 2021. http://hdl.handle.net/10019.1/103286.

MLA Handbook (7^th Edition):

Asmal, Laila. “Brain structural and white matter changes in first-episode schizophrenia and their demographic, clinical and cognitive correlates.” 2018. Web. 19 Jan 2021.

Vancouver:

Asmal L. Brain structural and white matter changes in first-episode schizophrenia and their demographic, clinical and cognitive correlates. [Internet] [Doctoral dissertation]. Stellenbosch University; 2018. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10019.1/103286.

Council of Science Editors:

Asmal L. Brain structural and white matter changes in first-episode schizophrenia and their demographic, clinical and cognitive correlates. [Doctoral Dissertation]. Stellenbosch University; 2018. Available from: http://hdl.handle.net/10019.1/103286

Stellenbosch University

3. Du Plessis, Stefan. Measuring the impact of HIV on the fronto-striatal system.

Degree: PhD, Psychiatry, 2016, Stellenbosch University

URL: http://hdl.handle.net/10019.1/100223

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ENGLISH SUMMARY : HIV infection remains a major contributor to the global health burden despite the introduction of effective prevention strategies and the effectiveness of… (more)

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ENGLISH SUMMARY : HIV infection remains a major contributor to the global health burden despite the introduction of effective prevention strategies and the effectiveness of combined antiretroviral therapy (cART). Of particular importance is the impact of HIV on the brain. While cART has been successful in treating the more severe forms HIV induced cognitive impairment, the minor forms of impairment are now more prevalent. There remains some controversy with regard to the latter. Being diagnosed in the absence of other symptoms, there is some doubt that this category of cognitive impairment is valid at all. As such, investigating HIV induced functional brain changes may be helpful in the study of these forms of impairment. Although functional magnetic resonance imaging (fMRI) studies have thus far shown various forms of functional impairment in the brain, how these impairments relate to one another is unclear. Many key aspects of HIV’s potential impact on the frontostriatal system remain unexplored. Our overall objective was therefore to investigate the early impact of HIV on the brain using fMRI as an objective measurement tool. First, we investigated the effects of HIV on the brain by performing a quantitative meta analysis of all suitable fMRI data. Next, we proceeded to investigate the fronto-striatal network based on the results of the meta-analysis by performing fMRI imaging in a sample of HIV+ participants and matched HIV negative controls. Participants performed a stop-signal anticipation and a monetary incentive delay task to investigate the impact of HIV on important sub-networks of the fronto-striatal system. Finally, we investigated the relationship between striatal dysfunction with structural brain changes. The results from the meta-analysis showed that HIV consistently affects the fronto-striatal system based on past fMRI studies. In subsequent studies, we demonstrated diminished functioning of the fronto-striatal networks involved in inhibition of voluntary movement as well as reward processing. Furthermore, this fronto-striatal dysfunction was also related to cortical atrophy often seen in HIV. Based on these findings, I therefore conclude that fronto-striatal dysfunction is a core component of HIV infection and needs to be considered in the assessment and management of all patients afflicted by this still very prevalent illness.

AFRIKAANSE OPSOMMING : MIV-infeksie dra by tot die globale gesondheid las, ten spyte van die bekendstelling van effektiewe voorkomende strategiee en die doeltreffendheid van gekombineerde antiretrovirale terapie (ART). Van besondere belang is die impak van MIV op die brein. Terwyl ART suksesvol was in die behandeling van die meer ernstige klassifikasie van MIV geassosieerde kognitiewe inkorting, is die subtiele klassifikasie van hierdie inkorting nou nog meer algemeen. Die diagnose van meer ernstige kognitiewe inkorting is tans nog kontroversieel. Sedert dit gediagnoseer word in die afwesigheid van funksionele inkorting, is daar tans twyfel of hierdie kategorie van…

Advisors/Committee Members: Emsley, Robin Alexander, Vink, Matthijs, Stellenbosch University. Faculty of Medicine and Health Science. Dept. of Psychiatry..

Subjects/Keywords: HIV infections; Brain – Localization of functions; Highly active antiretroviral therapy; UCTD

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Du Plessis, S. (2016). Measuring the impact of HIV on the fronto-striatal system. (Doctoral Dissertation). Stellenbosch University. Retrieved from http://hdl.handle.net/10019.1/100223

Chicago Manual of Style (16^th Edition):

Du Plessis, Stefan. “Measuring the impact of HIV on the fronto-striatal system.” 2016. Doctoral Dissertation, Stellenbosch University. Accessed January 19, 2021. http://hdl.handle.net/10019.1/100223.

MLA Handbook (7^th Edition):

Du Plessis, Stefan. “Measuring the impact of HIV on the fronto-striatal system.” 2016. Web. 19 Jan 2021.

Vancouver:

Du Plessis S. Measuring the impact of HIV on the fronto-striatal system. [Internet] [Doctoral dissertation]. Stellenbosch University; 2016. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10019.1/100223.

Council of Science Editors:

Du Plessis S. Measuring the impact of HIV on the fronto-striatal system. [Doctoral Dissertation]. Stellenbosch University; 2016. Available from: http://hdl.handle.net/10019.1/100223

Stellenbosch University

4. Ovenden, Ellen Susan. Investigating the functional significance of genome-wide variants associated with antipsychotic treatment response in schizophrenia.

Degree: MSc, Genetics, 2015, Stellenbosch University

URL: http://hdl.handle.net/10019.1/97704

► ENGLISH ABSTRACT: Schizophrenia is a debilitating disease affecting approximately 70 million people worldwide. Response to treatment, much like the disorder itself, is highly heritable, heterogeneous,… (more)

▼ ENGLISH ABSTRACT: Schizophrenia is a debilitating disease affecting approximately 70 million people worldwide. Response to treatment, much like the disorder itself, is highly heritable, heterogeneous, and poorly understood. Only 50% of patients respond well to medication, and extensive research has provided limited improvement on this figure. Advances in genetic technologies coupled with massive increases in study sample size have the potential to explain the “missing heritability” of both schizophrenia and treatment response. Genome-wide association studies (GWAS) are at the forefront of complex trait research, but have had minimal success in terms of explaining the biology of psychiatric drug response. Despite the majority of GWAS “hits” being located in noncoding regions, functional interpretation is usually restricted to the closest gene. The Encyclopedia of DNA Elements (ENCODE) project has recently shown that noncoding variation is not just a functional proxy of adjacent coding regions, but can have complex and pervasive regulatory effects. This study aimed to investigate the functionality of noncoding single nucleotide polymorphisms (SNPs) in schizophrenia treatment response. A novel bioinformatics pipeline incorporated coding and noncoding variants implicated in treatment response, regions of linkage disequilibrium (LD), regulatory data, and biological pathway predictions. Firstly, the literature was mined to identify all variants associated via GWAS with antipsychotic response, after which publically available data was employed to find markers in LD with these variants. This larger group of variants was analysed with bioinformatic tools such as RegulomeDB and rSNPBase to determine regulatory potential. Thereafter, affected gene targets and pathways were identified with DAVID and GeneMANIA. In order to investigate the findings further, the top predicted regulatory variants and their GWAS partners were genotyped with TaqMan® OpenArray® in a South African first episode schizophrenia (FES) cohort and analysed for associations with treatment outcomes. The bioinformatic portion of this study implicated a region on chromosome 4q24 associated with treatment-refractory schizophrenia through involvement of the nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NFKB1) gene. This gene is a master regulator involved in immunity and has over 200 gene targets. NFKB1 and immune dysregulation have both previously been implicated in schizophrenia, pointing to a genetic overlap between schizophrenia risk and antipsychotic treatment response. The most significant variants in the association analyses occurred at the 4q24 locus, with rs230493 and rs3774959 significantly associated with poor response in the negative symptom domain (P < 0.0001). These findings suggest a genetic link between persistent negative symptoms and treatment nonresponse. Additionally, a 14-variant haplotype containing these two polymorphisms was associated with 4.41% higher positive symptom severity. Not only do these results validate… Advisors/Committee Members: Warnich, Louise, Emsley, Robin, Stellenbosch University. Faculty of AgriSciences. Dept. of Genetics..

Subjects/Keywords: Schizophrenia – Genetic aspects; Pharmacogenetics; Antipsychotics treatment response; Human genetics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ovenden, E. S. (2015). Investigating the functional significance of genome-wide variants associated with antipsychotic treatment response in schizophrenia. (Masters Thesis). Stellenbosch University. Retrieved from http://hdl.handle.net/10019.1/97704

Chicago Manual of Style (16^th Edition):

Ovenden, Ellen Susan. “Investigating the functional significance of genome-wide variants associated with antipsychotic treatment response in schizophrenia.” 2015. Masters Thesis, Stellenbosch University. Accessed January 19, 2021. http://hdl.handle.net/10019.1/97704.

MLA Handbook (7^th Edition):

Ovenden, Ellen Susan. “Investigating the functional significance of genome-wide variants associated with antipsychotic treatment response in schizophrenia.” 2015. Web. 19 Jan 2021.

Vancouver:

Ovenden ES. Investigating the functional significance of genome-wide variants associated with antipsychotic treatment response in schizophrenia. [Internet] [Masters thesis]. Stellenbosch University; 2015. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10019.1/97704.

Council of Science Editors:

Ovenden ES. Investigating the functional significance of genome-wide variants associated with antipsychotic treatment response in schizophrenia. [Masters Thesis]. Stellenbosch University; 2015. Available from: http://hdl.handle.net/10019.1/97704

Stellenbosch University

5. Ojagbemi, Abel Akinsola. A prospective study of neurological abnormalities in a cohort of Nigerian patients with schizophrenia.

Degree: PhD, Psychiatry, 2014, Stellenbosch University

URL: http://hdl.handle.net/10019.1/86327

► ENGLISH ABSTRACT: Background The changes in cognition, brain structure, and neurological soft signs which are characteristic of schizophrenia appear to have been present before the… (more)

▼ ENGLISH ABSTRACT: Background The changes in cognition, brain structure, and neurological soft signs which are characteristic of schizophrenia appear to have been present before the onset of the phenotype. They therefore find relevance as potential vulnerability markers of the disease. Neurological soft signs are of particular interest because they can be elicited quickly, reliably and cheaply. They have also been touted as markers of certain characteristics of schizophrenia. The most convincing evidence for these assertions come from prospective longitudinal studies of first episode, medication naive patients with schizophrenia. Most of these studies have been based on wholly Caucasian or mixed samples of Caucasians and other races. The present study provides important reference data on the nature of neurological soft signs in indigenous African subjects and clarifies the trait or state marking signs in this population. Method A total of 84 patients with first episode, schizophrenia, schizo-affective disorder, or schizophreniform disorder meeting criteria in the fourth edition of the Diagnostic and Statistical Manual for Mental Disorders were consecutively recruited. Information on demographic characteristics, personal medical and psychiatric history, as well as family history was obtained at baseline. Neurological assessment was based on the 26 item Neurological Evaluation Scale. An exploratory factor analysis of the items in the scale was conducted using the baseline measurements. The derived sub-sets of neurological soft signs were then followed up longitudinally and in parallel with the ‘functional categories’ of the signs. The study describes the profile of neurological soft signs across the one year course of schizophrenia, as well as their relationship with a wide range of clinical and outcome variables. The severity of the baseline psychopathology was evaluated by administering the Positive and Negative Syndrome Scale. The overall clinical status was assessed using Clinical Global Impression. Additional assessments included the Calvary Depression Scale for Schizophrenia, Birchwood Insight Scale, Social and Occupational Functioning Assessment Scale, and the World Health Organisation Quality of Life Scale (WHO QoL-BREF). Pre-morbid adjustment was assessed using the Pre morbid Adjustment Scale, while extra-pyramidal effect of antipsychotics was assessed using the Extra-pyramidal Symptoms Rating Scale. Assessments were repeated at three monthly intervals for the full 12 months. Results Neurological soft signs were present in 96.4% of the sample at baseline. The signs loaded into a four factor structure: perceptual and motor sequencing (audio-visual integration, fist-edge palm, rhythm tapping, extinction, and right-left confusion), eye movements (synkinesis, convergence, and gaze impersistence), motor co-ordination and graphaesthesia (tandem walk, adventitious flow, and graphaesthesia), as well as stegreognosis. The scores for the perceptual and motor sequencing factor, as well… Advisors/Committee Members: Gureje, Oye, Emsley, Robin, Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Psychiatry..

Subjects/Keywords: Medicine; UCTD

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ojagbemi, A. A. (2014). A prospective study of neurological abnormalities in a cohort of Nigerian patients with schizophrenia. (Doctoral Dissertation). Stellenbosch University. Retrieved from http://hdl.handle.net/10019.1/86327

Chicago Manual of Style (16^th Edition):

Ojagbemi, Abel Akinsola. “A prospective study of neurological abnormalities in a cohort of Nigerian patients with schizophrenia.” 2014. Doctoral Dissertation, Stellenbosch University. Accessed January 19, 2021. http://hdl.handle.net/10019.1/86327.

MLA Handbook (7^th Edition):

Ojagbemi, Abel Akinsola. “A prospective study of neurological abnormalities in a cohort of Nigerian patients with schizophrenia.” 2014. Web. 19 Jan 2021.

Vancouver:

Ojagbemi AA. A prospective study of neurological abnormalities in a cohort of Nigerian patients with schizophrenia. [Internet] [Doctoral dissertation]. Stellenbosch University; 2014. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10019.1/86327.

Council of Science Editors:

Ojagbemi AA. A prospective study of neurological abnormalities in a cohort of Nigerian patients with schizophrenia. [Doctoral Dissertation]. Stellenbosch University; 2014. Available from: http://hdl.handle.net/10019.1/86327

Stellenbosch University

6. Rossouw, Liezel. The prevalence of burnout and depression among medical doctors working in the Cape Town Metropole community health care clinics and district hospitals of the Provincial Government of the Western Cape : a cross-sectional study.

Degree: MMed, Interdisciplinary Health Sciences, 2011, Stellenbosch University

URL: http://hdl.handle.net/10019.1/46747

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Aim: This study investigated burnout and depression among medical doctors in the context of work-related conditions and the role of resilience as a modifiable factor.… (more)

Subjects/Keywords: Physicians – Job stress – South Africa – Western Cape; Physicians – Health and hygiene – South Africa – Western Cape; Stress (Psychology); Burn out (Psychology)

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Rossouw, L. (2011). The prevalence of burnout and depression among medical doctors working in the Cape Town Metropole community health care clinics and district hospitals of the Provincial Government of the Western Cape : a cross-sectional study. (Thesis). Stellenbosch University. Retrieved from http://hdl.handle.net/10019.1/46747

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Rossouw, Liezel. “The prevalence of burnout and depression among medical doctors working in the Cape Town Metropole community health care clinics and district hospitals of the Provincial Government of the Western Cape : a cross-sectional study.” 2011. Thesis, Stellenbosch University. Accessed January 19, 2021. http://hdl.handle.net/10019.1/46747.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Rossouw, Liezel. “The prevalence of burnout and depression among medical doctors working in the Cape Town Metropole community health care clinics and district hospitals of the Provincial Government of the Western Cape : a cross-sectional study.” 2011. Web. 19 Jan 2021.

Vancouver:

Rossouw L. The prevalence of burnout and depression among medical doctors working in the Cape Town Metropole community health care clinics and district hospitals of the Provincial Government of the Western Cape : a cross-sectional study. [Internet] [Thesis]. Stellenbosch University; 2011. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10019.1/46747.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Rossouw L. The prevalence of burnout and depression among medical doctors working in the Cape Town Metropole community health care clinics and district hospitals of the Provincial Government of the Western Cape : a cross-sectional study. [Thesis]. Stellenbosch University; 2011. Available from: http://hdl.handle.net/10019.1/46747

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Stellenbosch University

7. Drogemoller, Britt Ingrid. Investigation of genetic variation contributing to antipsychotic treatment response in a South African first episode schizophrenia cohort.

Degree: PhD, Biology and Human Genetics, 2013, Stellenbosch University

URL: http://hdl.handle.net/10019.1/95473

► ENGLISH ABSTRACT: Schizophrenia is a debilitating disorder that occurs the world over. Although antipsychotics are largely effective in treating the positive symptoms of schizophrenia, the… (more)

▼ ENGLISH ABSTRACT: Schizophrenia is a debilitating disorder that occurs the world over. Although antipsychotics are largely effective in treating the positive symptoms of schizophrenia, the outcomes are non-optimal in many patients. As antipsychotic treatment response has been shown to be heritable, it is expected that the implementation of antipsychotic pharmacogenomics should aid in the optimization of antipsychotic treatments, however to date clinically applicable results are limited. Therefore this study utilized exome sequencing in a cohort of well characterized first episode schizophrenia patients to identify the genetic factors contributing to antipsychotic treatment response. The utility of exome sequencing for antipsychotic pharmacogenomic applications in the African context was assessed through examination of the literature and publically available data. Thereafter, a cohort of 104 well characterized South African first episode schizophrenia patients who were treated with flupenthixol decanoate for twelve months was collected. From this cohort, subsets of patients on extreme ends of the treatment response spectrum were identified for exome sequencing. Thereafter a bioinformatics pipeline was used to call and annotate variants. These variants and those that have previously been associated with antipsychotic response, along with a panel of ancestry informative markers, were prioritized for genotyping in the entire cohort of patients. After genotyping of the 393 variants, statistical analyses were performed to identify associations with treatment response outcomes. Examination of the literature revealed a need for exome sequencing in Africa. However, critical analyses of next generation sequencing data demonstrated that complex regions of the genome may not be well suited to these technologies. Thus, it may be necessary to combine exome sequencing with knowledge obtained from past research, as was done in this study to identify the genetic factors contributing to antipsychotic treatment response. Using this strategy, the current study highlighted the potential role that rare variants play in antipsychotic treatment response and additionally detected 11 variants that were significantly associated with antipsychotic treatment response outcomes (P=2.19x10-5). Nine of these variants were predicted to alter the function of the genes in which they occurred; of which eight were novel with regards to antipsychotic treatment response. The remaining two variants have been associated with antipsychotic treatment outcomes in previous GWAS. Examination of the function of the genes in which the variants occurred revealed that the variants associated with (i) positive symptom improvement were involved in the folate metabolism pathway and (ii) negative and general pathological symptoms improvement had potential links to neuronal development and migration. To our knowledge this study is the first to utilize exome sequencing for antipsychotic pharmacogenomic purposes. The ability of this study… Advisors/Committee Members: Warnich, Louise, Emsley, Robin, Niehaus, Dana, Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biology and Human Genetics. Molecular Biology and Human Genetics..

Subjects/Keywords: Antipsychotics; Schizophrenia; Pharmacogenetics; Exome sequencing; Department of Genetics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Drogemoller, B. I. (2013). Investigation of genetic variation contributing to antipsychotic treatment response in a South African first episode schizophrenia cohort. (Doctoral Dissertation). Stellenbosch University. Retrieved from http://hdl.handle.net/10019.1/95473

Chicago Manual of Style (16^th Edition):

Drogemoller, Britt Ingrid. “Investigation of genetic variation contributing to antipsychotic treatment response in a South African first episode schizophrenia cohort.” 2013. Doctoral Dissertation, Stellenbosch University. Accessed January 19, 2021. http://hdl.handle.net/10019.1/95473.

MLA Handbook (7^th Edition):

Drogemoller, Britt Ingrid. “Investigation of genetic variation contributing to antipsychotic treatment response in a South African first episode schizophrenia cohort.” 2013. Web. 19 Jan 2021.

Vancouver:

Drogemoller BI. Investigation of genetic variation contributing to antipsychotic treatment response in a South African first episode schizophrenia cohort. [Internet] [Doctoral dissertation]. Stellenbosch University; 2013. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10019.1/95473.

Council of Science Editors:

Drogemoller BI. Investigation of genetic variation contributing to antipsychotic treatment response in a South African first episode schizophrenia cohort. [Doctoral Dissertation]. Stellenbosch University; 2013. Available from: http://hdl.handle.net/10019.1/95473

Stellenbosch University

8. Kinnear, C. J. (Craig John). Molecular genetic strategies to identify Obsessive-compulsive disorder (OCD) and schizophrenia candidate genes in a South African sub-population group.

Degree: Biomedical Sciences, 2007, Stellenbosch University

URL: http://hdl.handle.net/10019.1/21666

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Dissertation (PhD) – University of Stellenbosch, 2007.

ENGLISH ABSTRACT: Obsessive-compulsive disorder is a severe, debilitating psychiatric disorder for which the underlying molecular aetiology still remains unclear.… (more)

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Dissertation (PhD) – University of Stellenbosch, 2007.

ENGLISH ABSTRACT: Obsessive-compulsive disorder is a severe, debilitating psychiatric disorder for which the underlying molecular aetiology still remains unclear. Evidence from family studies have suggested that OCD may be caused by a complex interplay of environmental and genetic factors. In order to identify the genetic factors that mediate OCD susceptibility, several genetic association studies have been undertaken, which have yielded inconsistent findings. Moreover, the majority of these studies have focused on a small number of candidate genes that encode components of the serotonin and dopamine neurotransmitter pathways. However, based on the complexity of clinical manifestations observed in OCD, it is likely that its pathogenesis is mediated by a broader complex of interrelated neurotransmitter systems and signal transduction pathways; consequently there is a need to identify and assess novel candidate genes. One method of identifying such novel OCD candidate genes is by utilising knowledge of diseases with phenomenological overlap with OCD, which lend themselves to better genetic dissection through linkage analysis and animal studies. Genetic loci for such disorders, identified though linkage analysis, could potentially harbour novel OCD candidate genes, while genes implicated through animal models may lead to the identification of additional susceptibility genes through delineation of pathways by, for instance, interactome analysis. One such disorder is schizophrenia, which manifests overlap in both symptoms and brain circuits with OCD. In schizophrenia, in addition to several case-control association studies having been performed, linkage data, studies of chromosomal aberrations and animal models have led to the identification of many chromosomal regions that may contain genes involved in its aetiology and thus may also contain OCD candidate genes. In the present investigation, this approach was employed using previously reported schizophrenia susceptibility loci to identify novel OCD candidate genes. All genes residing in each of these loci were catalogued and individually analysed using a battery of bioinformatic techniques in order to assess their potential candidature for OCD susceptibility. These analyses yielded 13 credible OCD candidate genes.Additional candidates were sought using information regarding a well-defined schizophrenia animal model, the heterozygous reeler mouse, that exhibits neurodevelopmental, neuroanatomical and behavioural abnormalities, similar to those displayed by patients with schizophrenia. The phenotype of these mice is caused by a mutation in Reln, which encodes reelin, a large extracellular matrix protein that plays a pivotal role in the ordered migration of neurons during the development of laminar brain structures. The fact that both reelin protein and mRNA levels have been shown to be reduced in post-mortem brain sections of schizophrenic patients, coupled with the observed behaviour…

Advisors/Committee Members: Moolman-Smook, Johanna C., Corfield, Valerie A., Emsley, Robin A., Stellenbosch University. Faculty of Health Sciences. Dept. of Biomedical Sciences..

Subjects/Keywords: Medicine; Dissertations – Medicine

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APA (6^th Edition):

Kinnear, C. J. (. J. (2007). Molecular genetic strategies to identify Obsessive-compulsive disorder (OCD) and schizophrenia candidate genes in a South African sub-population group. (Thesis). Stellenbosch University. Retrieved from http://hdl.handle.net/10019.1/21666

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Kinnear, C J (Craig John). “Molecular genetic strategies to identify Obsessive-compulsive disorder (OCD) and schizophrenia candidate genes in a South African sub-population group.” 2007. Thesis, Stellenbosch University. Accessed January 19, 2021. http://hdl.handle.net/10019.1/21666.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Kinnear, C J (Craig John). “Molecular genetic strategies to identify Obsessive-compulsive disorder (OCD) and schizophrenia candidate genes in a South African sub-population group.” 2007. Web. 19 Jan 2021.

Vancouver:

Kinnear CJ(J. Molecular genetic strategies to identify Obsessive-compulsive disorder (OCD) and schizophrenia candidate genes in a South African sub-population group. [Internet] [Thesis]. Stellenbosch University; 2007. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10019.1/21666.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kinnear CJ(J. Molecular genetic strategies to identify Obsessive-compulsive disorder (OCD) and schizophrenia candidate genes in a South African sub-population group. [Thesis]. Stellenbosch University; 2007. Available from: http://hdl.handle.net/10019.1/21666

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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