Thesis (PhD)-- Stellenbosch University, 2014. / ENGLISH ABSTRACT: Schizophrenia is a phenotypically heterogeneous disorder believed to have a strong genetic component. Limiting its clinical heterogeneity by means of subtyping may help to shed light on some of the genetic underpinnings of the disease. This study describes the application of factor analysis (FA), latent class analysis (LCA) and factor mixture modeling in a sample of 734 Xhosa-speaking schizophrenic subjects using factor analytically derived variables previously identified in an independent sample of this population. LCA was performed on the following 8 SANS and SAPS items identified by preliminary exploration of the data: eye contact, auditory hallucinations, global hallucinations score, global delusions score, grooming, affective non-responsiveness, spontaneous movement, and commenting voices. A four class model provided the best fit. Classes 1 and 2 were characterized by predominantly positive and predominantly negative symptoms, respectively, class 3 by both positive and negative symptoms and class 4 by few or absent symptoms. A history of cannabis use or abuse increased the probability of a subject being allocated to class 1, while being male made a person more likely to be included in class 2. Factor mixture modelling was performed by first using latent class analysis, then factor analysis and then the factor mixture analysis were done. The fit among these three types were then investigated. The results show that factor mixture modelling uncovered a heterogeneous latent variable structure that fits the data well with the latent classes capturing distinct positive symptom/behaviours and factors capturing severity variations. This study, the first to report on the latent class structure of schizophrenia in a sample of patients from a sub-Saharan African population, supports the universality of specific latent classes across ethnic boundaries. The results further support reports that gender, sibpair status and cannabis use may influence the phenomenology of schizophrenia. The identification of subgroups may represent an intermediate step in the search for endophenotypes of schizophrenia. / AFRIKAANSE OPSOMMING: Skisofrenie is „n psigiatriese steuring met „n heterogene fenotipe en „n vermoedelik sterk genetiese vatbaarheid. Ten einde die lig te werp op die genetiese onderbou van skisofrenie word gepoog om die kliniese heterogenisiteit te beperk deur middel van subgroepering. Hierdie studie beskryf die gebruik van latente klas analise (LKA) in „n groep van 734 Xhosa-sprekendes met skisofrenie. Die LKA word baseer op die gebruik van veranderlikes wat deur middel van faktor analise op simptome in „n onafhanklike studiegroep van Xhosa-sprekendes met skisofrenie verkry is. Die LKA is gedoen op die volgende 8 “SAPS” en “SANS” veranderlikes wat deur voorlopige ondersoek van die data ge-indentifiseer is: oogkontak, gehoorshallusinasies, globale hallusinasie telling, globale waantelling, selfversorging, affektiewe nie-responsiwiteit, spontane beweging en stemme wat kommentaar lewer. „n Vierklas oplossing het die beste passing getoon. Klas 1 en 2 is gekenmerk deur oorwegend positiewe en negatiewe simptome onderskeidelik, klas 3 het beide positiewe en negatiewe simptome gehad en klas 4 het baie min of geen simptome getoon nie. „n Geskiedenis van kannabis gebruik of misbruik het die kans verhoog dat die individue in klas 1 gevind sou word, terwyl manlike geslag as veranderlike die kanse verhoog het vir allokasie in klas 2. Faktor mengsel modelering is gedoen deur eers „n latent klas analise te voltooi, gevolg deur „n faktor analise, en laastens „n factor mengsel analise. Die passing tussen die drie analises is daarna evalueer. Faktor mengsel modelering toon „n heterogene latente klas struktuur wat voldoen aan die passingsvereistes. Die latente klasse blyk spesifieke positiewe simptome/gedrag te verteenwoordig, terwyl die factor grad van erns variasie aandui. Hierdie studie is die eerste om die latente klas struktuur van skisofrenie in „n subsahara-Afrika populasie, die Xhosa, te beskryf. Die resultate onderstreep die universialiteit van die latente struktuur van skisofrenie se simptome oor etniese grense heen. Verder ondersteun die resultate die moontlike rol van geslag, aangetaste sibstatus en kannabis gebruik in skisofrenie se fenomenologie. Die identifisering van die subgroepe mag „n intermediêre stap in die soektog vir endofenotipes van skisofrenie verteenwoordig.

Schizophrenia cuts across all racial, gender, and socioeconomic lines. Schizophrenia affects 1 percent of the population in Ireland: 35000 people (Schultz & Andreason, 1999); and affects 1.4 - 4.6 percent per 1000 people in the USA: 2.8 million - 9.8 million people (Jabelensky, 2004). In South Africa the figure is approximately 1 percent of the population or 500 000 people (Nicholas, Malcolm, Krosigk & Pillay, 2003). The median age of onset is 21.4 years for men and 26.8 years for women (Daubenton & van Rensburg, 2001), with only 10-20 percent recovering fully after the first psychotic episode (Saddock & Saddock, 2003). The schizophrenic patient is often unable to continue life as before diagnosis, and may progressively need more care as the years pass. Deinstitutionalization over the course of a number of decades has resulted in responsibility for care of mentally-ill individuals shifting to the individual’s family. The struggles faced by such a family can be overwhelming as they struggle with this responsibilty due to lack of training, lack of knowledge and insufficient professional support (Winefield & Harvey, 1994). The stress on the caregivers is often magnified as their support structures around them may ‘shut down’ out of fear of the schizophrenic illness (Williams & Mfoafo-M’Carthy, 2006). The characteristic symptoms used to define schizophrenia include various forms of delusions, hallucinations, thought disorders and abnormalities in emotional expression, social interaction, attention, volition and drives. The functional decline of the schizophrenic individual leads not only to social difficulties, but also economic difficulties that may cripple a family (Fadden, Bebbington & Kuipers, 1987). When first diagnosed, some families may be so overwhelmed by the ‘label’ given to their family member, that they see little hope or way to move forward. One explanation is offered by an American psychiatrist whose own son was diagnosed with schizophrenia, “We experience this terrible feeling of loss and grief for the son we knew. There is also this terrible loss of expectations. We feel cheated out of watching him mature…it is a mourning without end because, of course, Gary is not dead at all. He is very much still with us, seeming eternally twelve years old, needing constant care and attention” (Willick, 1994, p.14). Providing such care is associated with high levels of distress. Accordingly, much attention has been given to understanding the pressures faced by family members, with the hope of understanding how coping resources may be strengthened to sustain these care-giving relationships (Harvey, Burns, Fahy, Manley & Tattan, 2001). However, despite gains in understanding the needs of a schizophrenic family member once out of the hospital environment, care-giving relationships can still break down. The individual with the illness is often left more vulnerable to relapse, recurrent hospitalizations, homelessness and other negative outcomes (Jewel & Stein, 2002). The stress of not only interacting with the afflicted family member, but also with the grief associated with the illness, places an incredible strain on the day-to-day functioning of that family (Pollio, North, Reid, Miletic & McClendon, 2006). From the brief review provided, it is evident that research has been conducted regarding the stressors, strains and difficulties of caregivers of schizophrenic family members. However, the strengths of these families are under-investigated, and the current study will attempt to start filling this void.

Thesis (DMed (Psychiatry))--University of Stellenbosch, 2005. / BACKGROUND Schizophrenia is a heterogeneous disorder, which has been shown to have both environmental and genetic risk factors. Since family history (genetic loading) of psychosis appears to be one of the strongest risk factors for the development of schizophrenia, the investigation of affected sib pairs can be used to explore shared familial factors. The Xhosa-speaking inhabitants in the Western, Eastern and Southern Cape provinces, an African population of relatively homogeneous ethnicity, provided a sample of the first large clinical phenotype of schizophrenia. AIM The main aim of this study was to identify shared symptoms or symptom clusters in a sample of Xhosa-speaking sib pairs, with the aid of structured assessment tools.

Thesis (MSc (Genetics))—University of Stellenbosch, 2007. / No obvious explanations exist for the development of abnormal involuntary movements (AIM), but several hypotheses have been proposed for tardive dyskinesia (TD) development. Since TD seems to have a genetic basis, several genetic variants have been investigated in TD development in various populations. Few studies have focused on African populations. This study focused on genetic variants (previously investigated in other populations) and the development and severity of AIM and TD in a Xhosa schizophrenia population. Genotype and allele frequencies determined were compared to those described in the literature for other populations. Following a report of an association between Ala-9Val and schizophrenia in a Turkish population, this study subsequently investigated this association in the Xhosa population. MnSOD Ala-9Val was genotyped using HEX-SSCP analysis and the DRD3 Ser9Gly variant was genotyped using restriction enzyme digestion by MscI. Genotyping was followed by statistical comparisons of the various groups, as well as association analyses between the variant and schizophrenia (only for MnSOD), AIM, or TD development and severity. The groups included a Xhosa schizophrenia group, a subgroup of the Xhosa schizophrenia group that had AIM (AIM+) and did not have AIM (AIM-), a subgroup of the AIM+ group that had TD (TD+), and a healthy Xhosa control group. A possible interaction between Ala-9Val and Ser9Gly in the development of AIM and TD was also investigated. Lastly, it was attempted to genotype CYP2D6*4, CYP2D6*10 and CYP2D6*17 using various PCR methods followed by restriction enzyme analysis. MnSOD Ala-9Val genotype and allele frequencies were similar to those of the Turkish population, but differed to those of the Asian populations. No association between Ala-9Val and the development and severity of schizophrenia was found. However, a relationship between genotype and AIM or TD development was observed, as well as an association between TD severity and Ala- 9Val genotype. DRD3 Ser9Gly genotype and allele frequencies were similar to those of the African American population, but differed from other populations. No significant association between Ser9Gly and the development and severity of AIM or TD was detected, nor was an interactive effect between Ala-9Val and Ser9Gly in AIM or TD development observed. The genotyping of CYP2D6 proved difficult and these variants could therefore not be analysed. The CYP2D6*4 genotype and allele frequencies that could be determined from some samples, were similar to the frequencies described previously for African populations. While we did not find an association between Ser9Gly in TD or AIM development and severity, nor an interaction between Ala-9Val and Ser9Gly, we did observe a relationship between Ala-9Val and AIM or TD development and TD severity. The effect of this variant is probably small and other variants, specifically those in genes involved in free radical removal should be investigated in combination with Ala-9Val. With regard to CYP2D6 it is suggested that high-throughput genotyping methods (e.g. microarray technology) should be used in the future. This will enable simultaneous genotyping of several variants and can be used in various populations. This study is the first of its kind by focusing on the unique South African Xhosa population and TD or AIM development.

The system of care for persons suffering from schizophrenia is in a state of upheaval and the community in general is visibly frightened of an illness it knows little about except for the information acquired often from media reporting. Considering persons suffering from schizophrenia as holistic beings, this study explored and assessed the needs of these persons residing in the Mogoto Village, Zebediela District in the Northern Province. The primary purpose of the study was to explore and describe the holistic needs of persons suffering from schizophrenia thus facilitating the planning of care and care facilities for these individuals to enable them to function optimally in the community. To accomplish this purpose, specific objectives were formulated. A quantitative, exploratory and descriptive study based on the Nursing Theory for the Whole Person was carried out. Through purposive sampling 60 respondents were selected. A questionnaire was administered to the respondents. Data from questionnaires revealed that despite the diagnosis of schizophrenia, the respondents were still regarded as valuable members of the community by those who cared for them. There was also an indication that the needs of persons suffering from schizophrenia in the Mogoto Village did not differ from the needs of other persons in the rest of the world. Like any unique person they have specific needs. There was also an indication that mental illness is still rated low in the prioritisation of health problems, hence the lack of resources and support needed for the rehabilitation of persons suffering from schizophrenia, especially in the rural areas. / Advanced Nursing Sciences / M.A.(Nursing Science)

The system of care for persons suffering from schizophrenia is in a state of upheaval and the community in general is visibly frightened of an illness it knows little about except for the information acquired often from media reporting. Considering persons suffering from schizophrenia as holistic beings, this study explored and assessed the needs of these persons residing in the Mogoto Village, Zebediela District in the Northern Province. The primary purpose of the study was to explore and describe the holistic needs of persons suffering from schizophrenia thus facilitating the planning of care and care facilities for these individuals to enable them to function optimally in the community. To accomplish this purpose, specific objectives were formulated. A quantitative, exploratory and descriptive study based on the Nursing Theory for the Whole Person was carried out. Through purposive sampling 60 respondents were selected. A questionnaire was administered to the respondents. Data from questionnaires revealed that despite the diagnosis of schizophrenia, the respondents were still regarded as valuable members of the community by those who cared for them. There was also an indication that the needs of persons suffering from schizophrenia in the Mogoto Village did not differ from the needs of other persons in the rest of the world. Like any unique person they have specific needs. There was also an indication that mental illness is still rated low in the prioritisation of health problems, hence the lack of resources and support needed for the rehabilitation of persons suffering from schizophrenia, especially in the rural areas. / Advanced Nursing Sciences / M.A.(Nursing Science)