Thesis (PhD)--Stellenbosch University, 2015. / 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 characterised by higher levels of symptomatology in all domains; poorer functional outcome, poorer quality of life and greater cognitive impairments. They also had more prominent NSS and a lower BMI. The strongest predictors of non-response were prominent baseline NSS and poor early (7 weeks) treatment response. In conclusion, the combination of an LAI with an AMP may be an effective and safe intervention in firstepisode schizophrenia, and may be particularly suitable for resource-constrained settings. The risk of weight gain and metabolic syndrome associated with antipsychotic treatment in first-episode schizophrenia are not restricted to second generation antipsychotics and low-potency first-generation antipsychotics. Ensuring effective treatment for first episode schizophrenia patients is a global problem, and likely to be under-recognised in LMICs. / AFRIKAANSE OPSOMMING: Oor die afgelope twee dekades het toenemend meer longitudinale kliniese studies, wat eerste episode skisofrenie bestudeer, die lig gesien. Die studies het ‘n magdom van waardevolle inligtng oor die kliniese voorkoms, behandeling, verloop en uitkomste van die siekte opgelewer. Die meerderheid van die studies is egter in hoë inkomste ontwikkelde lande gedoen met pasiënte wat duur medikasie gebruik en hoofsaaklik in heterogene steekproewe. Alhoewel dit blyk uit hierdie studies dat daar oor die algemeen vordering gemaak word ten opsigte van die behandeling van pasiënte is daar steeds ‘n gebrek aan voldoende inligting oor die onderwerp veral in minder gegoede, ontwikkelende lande. Die oorhoofse doel van hierdie proefskrif is om binne ‘n hulpbron beperkte konteks die kliniese, biologiese en funksionele aspekte van pasiënt -uitkomste in eerste episode skisofrenie te ondersoek. Ons het ‘n longitudinale studie gedoen waarin ons die effektiwiteit en toleransie van ‘n enkele antipsigotiese medikasie vir 12 maande nagevors het. Die medikasie wat ons ondersoek het, is flupenthixol decanoate en word deur ‘n inspuiting gegee en die medikasie word dan geleidelik deur die liggaam geabsorbeer. As deel van die behandeling het ons pasiënte ook streng gemonitor. Ons het die effektiwiteit van die behandeling gemeet nagelang van hoe pasiënte reageer op die behandeling, hoeveel pasiënte in remissie gaan en terugval, en ook pasiënte se kwaliteit van lewe en hulle sosiale en beroepsfunksionering. Ons het toleransie gemeet nagelang van pasiënte se gewig en metaboliese verandering sowel as die voorkoms van medikasie geïnduseerde newe-effekte. Verder het ons pasiënte wat nie op medikasie gereageer het nie ondersoek sowel as die aspekte wat moontlik hiernee verband hou. Ons het bevind dat die meerderheid van pasiënte hulle medikasie getrou geneem het en ook die streng monitering aanvaar het. Sewentig persent van die pasiënte het hulle 12 maande behandeling voltooi, 82% het op die medikasie gereageer en 60% het in remissie ingegaan. Alhoewel 19% van die pasiënte teruggeval het, was dit nie so ernstig dat ons hulle moes hospitaliseer nie. Pasiënte het beduidende verbetering ten opsigte van hulle kwaliteit van lewe en sosiale en beroepsfunksionering getoon. Ons het slegs ‘n gematigde mate van medikasie geïnduseerde newe-effekte opgemerk en alleenlik by ‘n derde van die kohort. In die meerderheid van gevalle het ons die newe-effekte met anticholinergics of propranolol behandel. Slegs 3% van die pasiënte het gedurende die verloop van 12 maande die kondisie transient dyskinesia ontwikkel. Ongelukkig het ons kohort geweldig baie gewig opgetel en die toename in pasiënte se BMI (p< .0001) en middellyf omtrek (p=0.0006) was statisties beduidend. Ons het ook bevind dat veranderinge in ons kohort se lipied profiele kommerwekkend is veral as in ag geneem word dat die toename in trigliseriede (p = 0,03) en die beduidende afname in die hoë digtheid lipoproteïen (p = 0,005) gelei het tot ‘n 91% verhoging in trigliseriede: hoë digtheid lipoproteïen verhouding.

Thesis (PhD (Psychiatry))--Stellenbosch University, 2008. / BACKGROUND: Schizophrenia is a heterogeneous illness resulting from complex gene-environment interplay. The majority of molecular genetic work done has involved Caucasian populations, with studies in these and Asian populations showing 2-32% of sufferers to have chromosomal aberrations. So far the discovery of a specific susceptibility mechanism or gene still eludes us, but the use of endophenotypes is advocated as a useful tool in this search. No cytogenetic studies of this nature have been reported in any African schizophrenia population. AIM: The aim of the study was to combine genotypic and phenotypic data, collected in a homogenous population in a structured manner, with the hope of characterising an endophenotype that could be used for more accurate identification of individuals with possible chromosomal abnormalities. METHODOLOGY: A structured clinical interview was conducted on 112 Xhosa schizophrenia patients. (Diagnostic Interview for Genetic Studies, including Schedules for the Assessment of Negative and Positive Symptoms.) Blood samples (karyotyping and/or FISH analysis) as well as urine samples (drug screening) were obtained and nine head and facial measurements were performed. Descriptive statistics were compiled with reference to demographic, clinical and morphological variables. Comparisons between mean differences for these variables were made.