Thesis (PhD (Psychiatry))--University of Stellenbsoch, 2005. / Background: Obsessive-compulsive disorder (OCD) is a neuropsychiatric condition characterized by significant heterogeneity. It has been suggested that classification of OCD into more homogeneous subtypes, and identification of their associations with etiological factors (e.g. genetic variants, or psychological trauma), and outcome (e.g. disability and treatment response), may be useful. The identified subtypes are not definitive yet and continue to be subject to revision. The overall objective of this dissertation was to assess comprehensively a sample of OCD patients, and to use cluster analytic methods to delineate valid OCD subtypes. Methods: Patients meeting DSM-IV criteria for a primary diagnosis of OCD (N=261) on the Structured Clinical Interview for Axis I Disorders - Patient Version (SCID-I/P), with ages ranging from 16 to 71, took part in the study. The newly developed Structured Clinical Interview for the Diagnosis of putative Obsessive-Compulsive Spectrum Disorders (SCIDOCSD) was administered to assess OCD-related conditions not covered by the SCID-I/P. OCD subtyping, based on OCD symptomatology (assessed with the Yale-Brown Obsessive- Compulsive Symptom Checklist [YBOCS-CL]), and based on comorbidity with the OCD spectrum of disorders (assessed with the SCID-OCSD), proceeded along the following lines: Firstly, latent class cluster analysis (LCA), a categorical analogue to traditional factor analysis (FA), and with many advantages compared to FA, was implemented with the (nine) most frequently endorsed OC symptoms. Secondly, in an attempt to remedy some of the limitations of the LCA (e.g. increased potential for computational instability when additional indicators / symptoms were included), cluster analyses (Ward’s method) were performed on all of the items of the YBOCS-CL and SCID-OCSD, respectively, for all OCD patients. The associations of cluster scores with demographic variables (age, gender), clinical variables (age of onset, obsessive-compulsive symptom severity and dimensions, level of insight, temperament, childhood trauma, treatment response) and genotypes were then examined, using Spearman correlation coefficients, one-way analysis of variance (ANOVA), and Mann- Whitney U-tests, where appropriate. Results: The findings suggested that increased presentation of symptoms characteristic of each of the clusters of cases was associated with specific demographic and clinical characteristics, which substantiated the presence of distinct clinical subtypes of OCD. Cluster analysis of the 45 selected items of the YBOCS-CL in this sample of OCD patients identified 6 separate clusters; these clusters were labelled “Contamination fears / washing”, “Hoarding / collecting”, “Symmetry / ordering / counting / arranging / repeating”, “Sexual”, “Somatic, religious and diverse” and “Harm-related”. Increased presentation of symptoms characteristic of each of the clusters was associated with specific demographic, clinical and, in some cases, genetic characteristics. Of note, the findings indicated the L/L (met/met) genotype of COMT Val158Met polymorphism plays a major role in the increased manifestation of sexual, somatic, religious and diverse, and harm-related symptoms of OCD, as such contributing to the relatively limited data on OC symptom subtypes and genetics. However, the fact that the associated features did not clearly and uniquely differentiate clusters and that clusters were significantly correlated with one another suggested that the delineation of the OCD complex into OC symptom clusters is not the only way to approach the heterogeneity characteristic of OCD. Nevertheless, the significant comorbidity with OCSD’s in the identified clusters (e.g. tics associated with sexual obsessions / compulsions) highlighted the significant relationship of OCD with the OCSD’s. This again raised the question about the way in which the OCSD’s “fit” with the standard OC symptomatology outlined in the YBOCS-CL. A cluster analysis of OCSD’s in OCD patients identified a Tourette’s syndrome / tics subtype of OCD (part of the so-called “reward deficiency” cluster), as well as an impulsivity subtype, and a somatic subtype – each associated with specific clinical and demographic variables. Here, a significant relationship between the identified clusters and the investigated dopaminergic and serotonergic polymorphisms was not found, suggesting that variants in other genes in these systems should also be explored. Conclusion: The main finding was that OCD is indeed a heterogeneous disorder that may be subtyped into different symptom dimensions. The identified OCD subtypes with their associated features were to a large extent consistent with previously published data. However, in contrast to factor analysis, LCA provided a novel, appropriate and advantageous statistical analysis strategy for the data. Furthermore, to our knowledge, the attempt to classifiy OCD according to comorbid OCSD’s was the first cluster analysis based on a prospective comprehensive interview investigating a range of OCSD’s. As such, although the dimensional structure of OCD is still not entirely understood, the categorization of our OCD patients into different groups and the investigation of their respective features have gone beyond the literature and thus add another dimension to the increasing efforts to fully delineate OCD subtypes.

Thesis (PhD (Psychiatry))-- Stellenbosch University, 2006. / ENGLISH ABSTRACT: Obsessive-compulsive disorder (OCD), a debilitating psychiatric disorder, affects 2-3% of the general population, and represents a global health problem. Evidence from family studies suggests that genetic factors play a role in mediating disease development. However, the pattern of inheritance is not consistent with monogenic disorders, but is “genetically complex”. Case-control association analysis, which facilitates dissection of the genetic aetiology of complex disorders, has yielded many inconsistent results in OCD studies, making identification of predisposing alleles difficult. These discrepant findings can largely be attributed to inappropriate statistical methodology and the lack of OCD phenotypic resolution. Although classified as a single clinical entity according to structured algorithms, OCD probably represents a final common outcome of multiple underlying aetiologies. Thus, numerous clinical subtypes of the disorder have been proposed; these “intermediate” phenotypes may be more closely related to a particular genetic substrate than the higher order construct of OCD. Furthermore, although genes encoding serotonergic (5-HT) and dopaminergic components are most commonly investigated, it is likely that the behavioural manifestations of OCD are mediated by a broader network of interconnected neurotransmitter and signalling pathways. Consequently, the aim of the present study was two-fold: to address the factors that may have confounded previous genetic case-control association studies and to investigate the genetic aetiology of OCD phenotypes while accounting for these factors. Case and control individuals were drawn from the reportedly genetically homogeneous Afrikaner population. However, as no empirical evidence existed to support the absence of genetic substructure, which would confound genetic association studies, a Bayesian modelbased clustering algorithm (Structure), that groups individuals on the basis of observed genotype data, was employed to assess population stratification in both case and control Afrikaner subjects. OCD patients were clinically stratified by gender, symptom severity, age at onset, the presence of selected co-morbid disorders and the presence of selected symptom dimensions, to facilitate the identification of susceptibility genes more closely related with these subtypes. Candidate genes included those coding for components of the 5-HT (5-HT receptors 1Dβ, 2A, 2C and 6), dopaminergic (dopamine receptors 1, 2, 3 and 4, dopamine transporter and catechol-O-methyltransferase [COMT]), glutamatergic (glutamate receptor subunit 2B [GRIN2B]) and neurodevelopmental pathways (brain-derived neurotrophic factor [BDNF] and homeobox 8 [HoxB8]), as well as previously uninvestigated genes (angiotensinconverting enzyme I, inositol-trisphosphate, phospholipase-C-gamma 1 and estrogen receptor alpha). The relationship between variants in these genes and OCD (or OCD subtypes) was investigated in a single locus and a haplotype context, while meta-analyses using published population-based case-control association data were also conducted. Significant associations noted between distinct COMT variants and OCD implicated COMT in the development of a genetically discrete, gender-dependant, early-onset, tic-related phenotype in males. Furthermore, investigations of variations in BDNF and GRIN2B point towards a genetically distinct, neurodevelopmental subtype of the disorder, mediated, in males at least, primarily by dysfunctions in BDNF. The striking gender dimorphism noted in these associations indicates the possibility of an epigenetic hormonal influence. Moreover, the significant association of polymorphisms within GRIN2B, in both a single locus and haplotype context, suggests the involvement of this gene in mediating a phenotypic subtype characterised by an early-onset, more severe form of the disorder. The present investigation forms part of ongoing research to elucidate genetic components involved in the aetiopathology of OCD and OCD-related subtypes. Such studies may pave the way towards more efficacious pharmacotherapeutic strategies, which will ease the suffering of individuals who are afflicted with this incapacitating condition. / AFRIKAANSE OPSOMMING: Obsessiewe-kompulsiewe steuring (OKS) is 'n aftakelende psigiatriese siektetoestand wat 2- 3% van die algemene bevolking affekteer en 'n globale gesondheidsprobleem verteenwoordig. Familiestudies dui daarop dat genetiese faktore 'n rol in die ontwikkeling van hierdie siekte speel. Die patroon van oorerwing is egter nie verenigbaar met dié van monogeniese siektes nie, maar is geneties "kompleks". Geval-kontrole assosiasie-ontleding, wat die disseksie van die genetiese etiologie van komplekse siektes fasiliteer, het teenstrydige resultate in OKS gelewer en dit bemoeilik die identifikasie van predisponerende allele. Die teenstrydige bevindings kan grootliks aan ontoepaslike statistiese metodiek en die gebrek aan fenotipiese differensiasie in OKS toegeskryf word. Alhoewel dit volgens gestruktureer algoritmes as 'n enkele kliniese entiteit geklassifiseer word, verteenwoordig OKS waarskynlik die eindresultaat van veelvoudige onderliggende oorsake. Baie kliniese subtipes van die toestand is al voorgestel en dié "intermediêre' fenotipes mag nader verwant aan 'n spesifieke genetiese substraat as die hoër orde konsep van OKS wees. Verder, alhoewel die gene wat die serotonergiese (5-HT) en dopaminergiese komponente kodeer meestalondersoek word, is dit waarskynlik dat die gedragsmanifestasies van OKS deur 'n breër netwerk van intergekonnekteerde neuro-oordragstof- en seinoordragpaaie meegebring word Gevolglik was die doel van die huidige studie tweevoudig: om faktore wat vorige genetiese geval-kontrole assossiasie-studies verwar het aan te spreek en om die genetiese etiologie van OKS-fenotipes te ondersoek met in ag neming van hierdie faktore. Geval- en kontrole-individue is gekies uit die Afrikaner-bevolking wat as geneties homogeen beskryf kan word. Daar was geen empiriese bewyse vir die afwesigheid van 'n genetiese substruktuur (wat genetiese assossiasie-studies sou verwar),nie. Daarom is 'n Bayesiese model-gebaseerde groeperings-algoritme (Structure), wat individue op grond van waargenome genotipiese data groepeer, gebruik om die populasie-stratifikasie is beide gevalen kontrole- Afrikaner-individue te bepaal. OKS-pasiënte is klinies gestratifiseer volgens geslag, ernstigheid van simptome, ouderdom by aanvang van simptome, die teenwoordigheid van geselekteerde komorbiede siektetoestande en die teenwoordigheid van geselekteerde simptoomdimensies of -groepe, om die identifikasie van moontlike vatbaarheidsgene wat nader verwant is aan die verskillende subtipes te fasiliteer/vergemaklik. Kandidaatgene het ingesluit: dié wat kodeer vir komponente van die 5-HT-(5-HT reseptore IDB, 2A, 2C and 6), dopaminergiese (dopamienreseptore 1, 2, 3 and 4, dopamien-transporter and katesjol-O-metieltransferase [COMTJ), glutamatergiese (glutamaat-reseptor subeenheid 2B [GRIN2B]) and neuro-ontwikkelingspaaie (brein-gederiveerde neurotrofiese faktor [BDNF] en homeobox 8 [HoxB8]), sowel as die gene wat nie voorheen ondersoek is nie (angiotensien-omsettingsensiem I, inositol-trisfosfaat, fosfolipase-C-gamma 1 en estrogeen-reseptor alpha). Die verhouding tussen variante in hierdie gene en OKS (of OKS-subtipes) is ondersoek in 'n enkel-lokus en haplotipe konteks, en meta-analises, wat gepubliseerde bevolkings-gebaseerde geval-kontrole ontledingsdata gebruik het, is ook gedoen. Beduidende assosiasies gevind tussen spesifieke COMT-variante en OKS in mans, het daarop gedui dat COMT in die ontwikkeling van geneties-diskrete, vroeë-aanvang, senutrekking ("tics") -verwante fenotipe in mans betrokke is. Verder het ondersoeke van variasies in BDNF en GRIN2B daarop gedui dat 'n geneties-afsonderlike, neuro-ontwikkelings-subtipe van.OKS wat, ten minste in mans, primêr deur wanfunksie van BDNF meegebring word. Die opvallende geslags verskil wat in hierdie assosiasies gesien word, dui op die moontlikheid van 'n epigenetiese hormonale invloed. Bowendien, die beduidende assosiasie van polimorfismes in GRIN2B in beide die enkel-lokus en haplotipe konteks, dui op die betrokkenheid van hierdie geen in die meebring van 'n fenotipiese subtipe wat deur 'n vroeë aanvang, en meer ernstige vorm van die siekte gekenmerk word. Die huidige ondersoek vorm deel van voortgesette navorsmg om die genetiese komponente wat betrokke is by die etiopatologie van OKS en OKS-subtipes, bloot te lê. Sodanige studies kan die weg baan na meer doeltreffende farmakoterapeutiese strategieë wat die lyding van indi vidue wat deur hierdie aftakelende toestand geraak word, kan verlig.

Thesis (PhD (Psychiatry))--University of Stellenbosch, 2006. / Lipoid Proteinosis (LiP) is a rare hereditary disease, which often results in bilateral, symmetrical and circumscribed calcifications in the mesial temporal region (especially the amygdala). While several case studies have been published on individuals with this illness, there have been few systematic investigations of the neuropsychiatry and neuropsychology of a series of patients. Thirty-seven LiP patients were extensively assessed with standardized neuropsychiatric and neuropsychological measures. Of these, 27 patients from the Northern Cape in South Africa were matched (for age, gender, education, language, geographical area) with 53 controls. There was a high incidence of neuropsychiatric disorders in LiP (more than half of the subjects reported a history of depression or anxiety and 12% had a diagnosis of schizophrenia). Despite a wide variance, LiP subjects performed poorly on facial recognition for emotions and on most neuropsychological measures including intelligence, recall and executive functioning. These findings are consistent with involvement of the mesial temporal areas in mood, anxiety, and psychotic symptoms, and in the cognitive-affective processes. Future work aimed at delineating the associations between the clinical and neuropsychological findings reported here, for example, with brain-imaging techniques, is needed.

Thesis(DMed (Psychiatry))-- University of Stellenbosch, 2007. / Alcohol-induced psychotic disorder (also known as alcohol hallucinosis) is a complication of alcohol abuse that requires clinical differentiation from alcohol withdrawal delirium and schizophrenia. Although extensively described, few studies utilized standardized research instruments and brain-imaging has thus far been limited to case reports. The aim of this study was to prospectively compare four population groups (ie. patients with alcohol-induced psychotic disorder, schizophrenia, uncomplicated alcohol dependence and a healthy volunteer group) according to demographic, psychopathological and brainimaging variables utilizing (i) rating scales and (ii) single photon emission computed tomography (SPECT). The third component of the study was designed to investigate the (iii) effect of anti-psychotic treatment on the psychopathology and regional cerebral blood flow (rCBF) before and after six weeks of treatment with haloperidol. Effort was made to ensure exclusion of comorbid medical disorders, including substance abuse. The study provides further supportive evidence that alcohol-induced psychotic disorder can be distinguished from schizophrenia. Statistically significant differences in rCBF were demonstrated between the alcohol-induced psychotic disorder and other groups. Changes in frontal, temporal, parietal, occipital, thalamic and cerebellar rCBF showed statistically significant negative correlations with post-treatment improvement on psychopathological variables and imply dysfunction of these areas in alcohol-induced psychotic disorder. The study was unable to distinguish between pharmacological effects and improvement acccomplished by abstinence from alcohol. / Stellenbosch: Stellenbosch University

Thesis (MMed)--University of Stellenbosch, 2004. / ENGLISH ABSTRACT: Numerous tests exist for the assessment of general cognitive functioning. Most of these tests were developed within the discipline of psychology. Neuropsychological tests are very useful, but have some limitations. Administration of the tests is limited to a psychologist, is very timeconsuming in that it can take 3-8 hours to administer and often need specialized equipment. At the other end of the continuum are very brief screening tests. General practitioners, psychiatrists and occupational therapists, in addition to psychologists, also use these tests. Although useful, the short tests only provide limited information. An intermediate level test streamlining the assessment process between the very short and longer neuropsychological tests is therefore introduced by this study. The Bedside Cognitive Assessment Battery (BCAB) was developed in 1995 and are since used, at Tygerberg Hospital's Memory Clinic, to assess patients and teach students. The test comprehensively assesses the six main classes of cognitive functioning, namely attention and concentration, speech, memory, motor functioning, perceptual functioning and executive functioning. Approximately 35-45 minutes is required for administration and training is needed to administer the BCAB. No specialized equipment is needed for administration. The battery can therefore be used at the bedside, in the office or at old age homes. The aims of this study were to validate the BCAB for use with people aged eighteen years and older, and provide normative values for use in clinical settings. The test was revised in 1997 and 2001, and extensively so in 2002, but was never formally evaluated for validity. Well-known single tests were used to compile the BCAB. Most of these tests have proven validity and reliability, but only for foreign populations. In addition, some items were reformulated and others created by the researchers. The introduction of normative values would also be useful to assist in the delineation of cognitively intact and impaired individuals. This study succeeded in providing a table of normative values. One-hundred-and-sixty Afrikaans and English participants, and fourteen Xhosa participants were assessed in their mother tongue language. This project thus also introduced a Xhosa version of the BCAB. The purpose of the Xhosa version was to address the lack of culturally relevant cognitive assessment instruments. Results were evaluated for the effects of the variables' language, gender, age and education. The effect of language was most noticeable in the Xhosa group. Gender did not affect results as dramatically as age and especially, education. These significant effects on the aforementioned variables have been described in previous reports. The BCAB is thus relevant and useful as a detector of mild to moderate impairment. It can also be used to identify specific impairment. This can narrow down the investigation of psychologists, thus saving time and money. In addition, medical and nonmedical staff can use the BCAB. Some limitations were also identified. The sample used may limit the generalization of results. Some test items also need revision, along with further validation studies. Clinicians are therefore advised to use the BCAB only in addition to complete clinical examinations when making decisions regarding a patient's cognitive status. The BCAB appears to be a valid tool for bedside assessment. However, this study could only set the stage for further research, especially studies concerned with establishing normative values. / AFRIKAANSE OPSOMMING: Verskeie toetse bestaan vir die evaluering van algemene kognitiewe funksionering, waarvan die meeste ontwikkel is binne die sielkunde. Neuro-sielkundige toetse is baie bruikbaar, maar het sekere beperkings. Administrasie van die toetse is beperk tot sielkundiges, maar tydrowend weens 'n tydsduur van drie tot agt uur, en verg dikwels gespesialiseerde toerusting. Aan die ander kant is heelwat kart siftings-toetse beskikbaar. Aigemene praktisyns, sielkundiges en arbeidsterapeute, asook sielkundiges, gebruik dit. Hoewel bruikbaar, bied die kart toetse beperkte inligting. 'n lntermediere vlak toets om die evaluerings-proses tussen kart en langer neuro-sielkundige toetse te integreer word met hierdie studie beoog. Die Bedkant Kognitiewe Evaluasie Battery (BKEB) is in 1995 ontwikkel en gebruik in die Geheue-kliniek van die Tygerberg Hospitaal om pasiente te evalueer en studente op te lei. Die toets is gerig op die omvattende evaluering van die ses hoof-klasse van kognitiewe funksionering. Hierdie klasse omvat aandag en konsentrasie, spraak, geheue, motoriese funksionering, perseptuele funksionering en uitvoerende funksionering. Sowat 35 tot 45 minute word benodig vir administrasie terwyl opleiding vereis word vir die neem van die toets. Geen gespesialiseerde toerusting is nodig nie. Die battery kan dus by die bedkant, in die kantoor of in ouetehuise gebruik word. Die doelwitte van hierdie studie is om die BKEB te evalueer in gebruik by 18-jariges en ouer, en normatiewe waardes te bepaal vir gebruik in kliniese omgewings. Die toets is in 1997 en 2001 hersien. In 2002 is dit uitvoerig hersien, maar nooit ge-evalueer vir geldigheid nie. Bekende enkel-toetse is gebruik am die BKEB saam te stel. Dit is as geldig en betroubaar bewys, hoewel slegs onder buitelandse bevolkingsgroepe. Hierbenewens is sekere items herformuleer en ander bygewerk deur die navorsers. Normatiewe waardes sal oak handig wees in die afbakening van kognitief normaal-funksionerende en kognitief-ingekorte individue. Hierdie studie het daarin geslaag am 'n tabel van normatiewe waardes daar te stel. Een-honderd-en-sestig Afrikaans- en Engels-sprekendes, en 14 Xhosa-sprekendes is tydens hierdie studie in hulle moedertaal ge-evalueer. Hierdie projek het dus oak 'n Xhosaweergawe van die BKEB geskep. Die doel van die Xhosa-weergawe was am die gebrek aan 'n kultureel toepaslike kognitiewe instrument te beklemtoon. Resultate is ge-evalueer gedagtig aan veranderlikes soos taal, geslag, ouderdom en opleidingsvlak. Taal het die grootste invloed gehad op uitslae van Xhosa-deelnemers. Geslag het nie die uitslae so dramaties bernvloed soos ouderdom, en veral opleidingsvlak nie. Literatuur het meestal die groot uitwerking van hierdie veranderlikes bevestig. Die BKEB is dus relevant en handig in die naspeuring van ligte tot matige kognitiewe ingekortheid. Dit kan ook gebruik word om spesifieke kognitiewe ingekortheid te identifiseer. Die kan die omvang van ondersoek deur sielkundiges vernou, wat kan lei tot In groot besparing in tyd en geld. Hierbenewens kan mediese en nie-mediese personeel aangewend word in die gebruik van die BKEB. Sekere tekortkominge is ge·,dentifiseer. Die steekproef mag egter die veralgemening van die uitslae beperk. Sekere toets-items mag ook hersiening vereis, tesame met verdere geldigheid-studies. Kliniese praktisyns word daarom aangeraai om die BKEB slegs in aanvulling tot omvattende kliniese ondersoeke te gebruik vir besluite m.b.t. In pasient se kognitiewe status. Die BKEB kom voor as In geldige instrument vir bedkant evaluering. Hierdie studie kon egter slegs die tafel dek vir verdere ondersoek, veral t.o.v. studies wat poog om normatiewe waardes daar te stel.

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 (PhD)--Stellenbosch University, 2011. / ENGLISH ABSTRACT: The practice of psychometric testing of cognitive functioning in South Africa is hampered by the paucity of normative data that adequately characterize our ethnically, linguistically, socioeconomically, and educationally diverse population. The general aim of this study was to ascertain whether cognitive tests developed in settings outside of the Western Cape urbanized area have valid application for clinical and research purposes in that area. Strategies used to achieve that aim included: 1) translation, adaptation, and subsequent administration of a compendium of tests in a sample of typically developing, coloured and white, 12- to 15-yearold, Afrikaans- and English-speaking adolescents; 2) evaluation of the relative impact of sociodemographic factors (age, sex, language, quality of education, and race) on test performance and the consequent derivation of appropriately stratified normative data; and 3) evaluation of the cross-cultural utility of the normative data by comparing data collected from the study sample to norms derived from other populations. Results indicated that sex and language of testing impacted minimally on cognitive functioning. In contrast, the pervasive and deleterious impact of disadvantaged quality of education on cognitive performance within typically developing adolescents was clearly demonstrated. For participants with advantaged quality of education, coloured race was associated with lower performance on measures of intelligence, semantic fluency, and one measure of attention. Furthermore, the results provided evidence of age-related increments in cognitive performance, particularly after the age of 12. For cognitive measures that were significantly affected by language, race, and quality of education, trends of a downward continuum of performance were demonstrated, from highest to lowest, as follows: 1) English-white-advantaged; 2) Afrikaans-white-advantaged; 3) Englishcoloured- advantaged; 4) English-coloured-disadvantaged; 5) Afrikaans-coloured-advantaged; and 6) Afrikaans-coloured-disadvantaged. Cross-cultural comparisons of norms showed that for some tests, norms derived from other populations were suitable for use in the study sample. For other tests, however, results showed that for certain subgroups, it was essential to use the stratified norms derived from the study in order to prevent misdiagnoses. / AFRIKAANSE OPSOMMING: Die psigometriese toetsing van kognitiewe funksionering word in Suid-Afrika gekniehalter deur 'n gebrek aan normatiewe data wat ons etnies, taalkundig, sosio-ekonomies en opvoedkundig diverse bevolking genoegsaam tipeer. Die algemene doel van hierdie studie was om vas te stel of kognitiewe toetse wat in omgewings buite die Wes-Kaapse stedelike gebied ontwikkel is, ook vir kliniese en navorsingsdoeleindes binne hierdie stedelike gebied aangewend kan word. Hiervoor is onder meer die volgende strategieë gevolg: 1) 'n kompendium toetse is vertaal, aangepas en vervolgens afgeneem onder ’n toetsgroep tipies ontwikkelende, bruin en wit, 12- tot 15-jarige, Afrikaans- en Engelssprekende adolessente; 2) die relatiewe impak van sosiodemografiese faktore (ouderdom, geslag, taal, opvoedingsgehalte en ras) op toetsprestasie, en die gevolglike verkryging van toepaslik gestratifiseerde normatiewe data, is beoordeel en 3) die kruiskulturele nut van die normatiewe data is beoordeel deur die data wat van die toetsgroep in hierdie studie verkry is, te vergelyk met norme wat van ander populasies bekom is. Die resultate toon dat geslag en die taal waarin die toets afgeneem word 'n minimale uitwerking op kognitiewe funksionering het. Daarenteen is duidelik bewys dat swakker gehalte opvoeding ’n verreikende en skadelike uitwerking op die kognitiewe funksionering van tipies ontwikkelende adolessente het. By deelnemers met beter gehalte opvoeding blyk daar 'n verband te wees tussen die bruin rassegroep en laer prestasie wat betref maatstawwe van intelligensie en semantiese vaardigheid, asook een maatstaf van konsentrasie. Voorts lewer die resultate bewys van ouderdomsverwante toenames in kognitiewe prestasie, veral ná die ouderdom van 12. Wat betref kognitiewe maatstawwe wat beduidend deur taal, ras en opvoedingsgehalte beïnvloed is, is 'n afwaartse prestasiekontinuum opgemerk wat van hoog na laag soos volg daar uitsien: 1) Engels-wit-bevoordeel, 2) Afrikaans-wit-bevoordeel, 3) Engels-bruin-bevoordeel, 4) Engelsbruin- benadeel, 5) Afrikaans-bruin-bevoordeel en 6) Afrikaans-bruin-benadeel. Kruiskulturele normvergelykings toon dat, wat sommige toetse betref, die norme wat van ander populasies bekom is ook geskik was vir gebruik onder die toetsgroep in hierdie studie. Wat ander toetse betref, het die resultate egter getoon dat dit by bepaalde subgroepe noodsaaklik is om die gestratifiseerde norme wat uit die betrokke studie afgelei is te gebruik ten einde verkeerde diagnoses te voorkom.

Dissertation (PhD)--Stellenbosch University, 2003. / ENGLISH ABSTRACT: Although schizophrenia is traditionally viewed as an illness with a very poor prognosis, research over the last few years indicates that early intervention may substantially improve the long-term outcome of this disorder. Several studies suggest that patients with first-episode psychosis (FEP) are more sensitive to, and require lower doses of antipsychotic medications than patients with more chronic forms of illness. However, the optimal dose of first-generation anti psychotics in patients with FEP has not been explored extensively and continues to be a controversial subject. This study evaluated the efficacy and safety of low-dose haloperidol in a South African cohort with FEP. The study was conducted in two phases: Phase 1 was an open-label, naturalistic study of 57 subjects with FEP who were commenced on 1mg of haloperidol for 4 weeks, after which gradual escalation of doses were allowed, if required. Subjects who failed to respond at haloperidol 10mg per day were switched to thioridazine. Failure to respond to thioridazine 600mg per day was interpreted to indicate treatment resistance. These subjects were then commenced on clozapine. The principal finding of this phase of the study was that the majority of subjects could be stabilized and maintained on very low doses of haloperidol (1.7 ± 1.0 mg/day at 12 months and 1.3 ±0.8 mg/day at 24 months). Ratings for extra-pyramidal side-effects did not increase significantly from baseline over the duration of the study, except in the case of tardive dyskinesia (TD), where a substantial number of subjects (12.3%) developed TD within 12 months of starting treatment. Phase 2 of the study was a double-blind, randomized controlled trial of low-dose (2mg/day) versus "standard dose" (8mg Iday) haloperidol. Forty subjects were included in this phase of the study; 20 in each treatment arm. The main finding was that there were no significant differences in treatment reponse between the two treatment groups. There were, however, significant differences between the two treatment groups in extrapyramidal side effects (EPSE), with the 8mg per day group exhibiting significantly higher levels of EPSE than the 2mg per day group. This was manifested by significant differences in scores on the Extrapyramidal Symptom Rating Scale (ESRS) and the Simpson-Angus Rating Scale. Furthermore, subjects in the 8mg haloperidol per day group required significantly higher doses of anticholinergic medication and had significantly higher mean levels of prolactin at the end of the study period. This study indicates that a majority of subjects with first-episode psychosis can be treated and maintained successfully with very low doses of haloperidol. It also shows that low-dose treatment is as effective as, and better tolerated than, "standard" doses. Despite the success with the low-dose treatment, however, there was still a much higher than expected incidence of tardive dyskinesia, a serious and potentially irreversible side-effect of neuroleptic treatment. / AFRIKAANSE OPSOMMING: Hoewel skisofrenie tradisioneel gesien is as 'n siekte met 'n uiters swak prognose, dui navorsing oor die afgelope jare daarop dat vroeë ingryping die langtermynuitkoms van hierdie toestand drasties mag verbeter. Resultate van verskeie studies dui daarop dat pasiënte met eerste-episode psigose (EEP) nie net meer sensitief is vir antipsigotiese middels nie, maar ook laer dosisse daarvan benodig tydens behandeling as pasiënte met meer kroniese vorms van psigotiese siekte. Desondanks is die kwessie van die korrekte dosis van eerste generasie antipsigotika in hierdie groep nog onvolledig nagevors en bly dit 'n omstrede onderwerp. Hierdie studie het ten doel gehad om die effektiwiteit en veiligheid van lae dosis haloperidol in 'n Suid-Afrikaanse populasie van pasiënte met EEP te evalueer. Die studie is uitgevoer in twee fases: Fase 1 was 'n oop, naturalistiese studie van 57 pasiënte met EEP wat aanvanklik behandel is met 1mg haloperidol per dag vir 4 weke, waarna geleidelike verhoging van dosisse toegelaat is, soos nodig. Diegene wat nie bevredigende respons getoon het op haloperidol 10mg per dag nie, is oorgeskakel na tioridasien. Ontoereikende respons teen 600mg/dag tioridasien is geïnterpreteer as 'n aanduiding van behandelingsweerstandigheid en behandeling met klosapien is begin. Die belangrikste bevinding van hierdie fase van die studie was dat die meerderheid pasiënte gestabiliseer en in stand gehou kom word op baie lae dosisse haloperidol (1.7 ± 1.0 mg/dag op 12 maande en 1.3 ±0.8 mg/dag op 24 maande). Metings van ekstra-piramidale newe-effekte (EPNE) het nie beduidend toegeneem oor die duur van die studie nie, behalwe in die geval van tardiewe diskinese (TO), waar 'n beduidende aantal pasiënte (12.3%) TO ontwikkel het binne 12 maande na aanvang van behandeling. Fase 2 van die studie was 'n dubbelblinde, ewekansig gerandomiseerde studie waarin behandeling met lae dosis haloperidol (2mg/dag) vergelyk is met "standaard" dosis haloperidol (8mg/dag). Veertig pasiënte is ingesluit in hierdie fase van die studie, 20 in elke behandelingsarm. Die hoofbevinding was dat daar geen beduidende verskille in respons op behandeling was tussen die twee groepe nie. Daar was egter beduidende verskille in EPNE, waar die 8mg/dag groep beduidend hoër vlakke van EPNE gehad het as die 2mg/dag groep. Hierdie verskil in EPNE is aangedui deur 'n statisties beduidende verskil in tellings op die Extrapyramidal Symptom Rating Scale (ESRS) en die Simpson- Angus Rating Scale. Verder het pasiënte in die 8mg/dag groep beduidend hoër dosisse antikolinerge medikasie benodig en ook hoër gemiddelde prolaktienvlakke gehad teen die einde van studie. Hierdie studie dui dus daarop dat die meerderheid van pasiënte met EEP suksesvol behandel en in stand gehou kan word met baie lae dosisse haloperidol. Die studie wys ook daarop dat behandeling met lae dosisse net so effektief is en beter verdra word as behandeling met "standaard" dosisse. Ten spyte van die suksesvolle gebruik van lae dosisse medikasie het die studie egter ook getoon dat daar "n baie hoër as verwagte insidensie was van TO, "n emstige en potensieelonomkeerbare newe-effek van neuroleptiese behandeling.

Thesis (PhD (Psychiatry))--University of Stellenbosch, 2011. / ENGLISH ABSTRACT: Pregnancy is often accompanied by distressing psychological symptoms such as anxiety. These symptoms may result from changes in cognitive-affective processing, which in turn reflect hormonal changes during this time. However, findings on associations between psychological distress, cognitive-affective changes and hormones have been inconsistent. Furthermore, few studies have investigated the neural circuitry underlying distress and cognitive-affective processing in pregnancy. The prefrontal cortex (PFC) plays a specific role in regulating emotion. Determining the relationship between these changes in cognitive-affective processing and in prefrontal circuitry is important, given the high prevalence of depressive and anxiety disorders in pregnancy. The overall objective of this study was to investigate distressing psychological symptoms and their association with cognitive-affective processes and neurobiological changes over the course of pregnancy. Pregnant women with low risk singleton pregnancies were recruited from Midwife Obstetric Units in the Western Cape. Non-pregnant healthy controls were also recruited from the same demographic area. Distress levels were assessed using the K-10, Spielberger State -Trait Inventory, and Perceived Stress Scale. Subjectively experienced cognitive ability was asked about. Objective cognitive ability was assessed using standardized neuropsychological tests. Selective attention to threat such as fear and anger was assessed using a Facial Stroop Task. Neural circuitry was assessed using Near-Infrared Spectroscopy while viewing dynamic emotional facial expressions of threat (Emotion Recognition Task). Glucocorticoid (cortisol) and gonadal hormonal levels (estrogen, progesterone, and testosterone) were also determined at each trimester of pregnancy. Associations between distressing psychological symptoms, cognitive-affective processes and neurobiology were assessed using standard statistical methods. The main findings to emerge from this research were that, 1. pregnant women had significantly higher trait anxiety at trimester 2, compared to trimester 1 of pregnancy; 2. compared to non-pregnant women, pregnant women paid significantly more attention to fearful faces across trimesters, suggesting altered cognitive-affective processing in pregnancy compared to non-pregnancy; 3. pregnant women demonstrated significantly increased PFC activation in response to fearful and angry faces (all trimesters) that was particularly evident at trimester 2; 4. the PFC activation was, across trimesters, significantly correlated with distress and selective attention to threat; and 5. the PFC activation was, across trimesters, also significantly associated with increased glucocorticoid and gonadal hormone levels. The main findings of this study are consistent with previous literature insofar as distress has previously been associated with altered cognitive-affective processing and prefrontal cortex activation, but extend it by showing that emotional regulation is altered in pregnancy compared to the non-pregnant state. These data provide an important insight into distressing psychological symptoms and their associations with cognitive-affective processes, and changes in neural circuitry and in hormone levels in pregnancy. These findings are also the first to show that structures involved in emotional processing (e.g. the PFC) also play a role in the regulation of affect in pregnancy. Future research should explore the causal mechanisms underlying altered emotional regulation in pregnancy, and include pregnant women that are clinically depressed or anxious as comparison subjects. / AFRIKAANSE OPSOMMING: Swangerskap word dikwels geassosieër met stres-veroorsakende sielkundige simptome soos angstigheid. Hierdie simptome mag die gevolg wees van veranderinge in kognitief-affektiewe prosessering, wat op sy beurt mag dui op hormonale veranderinge. Bevindinge oor assosiasies tussen sielkundige stres, kognitief-affektiewe prosessering en hormone is tot dusver onbeslis. Voorts was min studies gerig op die neurologiese meganika onderliggend aan stres en kognitief-affektiewe prosessering tydens swangerskap. Die prefrontale korteks (PFK) het 'n spesifieke rol in die regulering van emosie. Die bepaling van spesifieke assosiasies tussen veranderinge in kognitief-affektiewe prosessering en in prefrontale regulering is belangrik, gegewe die hoë voorkoms van toestande soos depressie en angssteurings tydens swangerskap. Die doel met hierdie studie was 'n ondersoek na assosiasies tussen stres-veroorsakende sielkundige simptome, kognitief-affektiewe prosesse en neurobiologie tydens swangerskap. Swanger vroue met lae risiko enkel-swangerskappe is gewerf by klinieke in Wes-Kaapland. Gesonde nie-swanger vroue is uit dieselfde omgewing gewerf as kontroles. Angs-vlakke is geevalueer met behulp van die K-10; die Spielberger State-Trait Inventory en die Perceived Stress Scale. Vrae is tydens ondersoeke gevra oor subjektief-ervaarde kognitiewe vermoë. Voorts is kognitiewe vermoë geëvalueer met behulp van gestandardiseerde neurosielkundige toetse. Hierbenewens is selektiewe aandag aan bedreigende gesigte wat vrees en woede toon, geëvalueer met behulp van 'n Facial Stroop Task. Neurologiese funksie is geëvalueer met gebruik van Na-Infrarooi Spektroskopie terwyl dinamiese bedreigende emosionele gesigsuitdrukkings vertoon is (Emotion Recognition Task). Gluko-kortikoïed (kortisol) en geslagshormoonvlakke (estrogeen, progesteroon, en testosteroon) is gemeet tydens elke trimester. Verwantskappe tussen stresvolle simptome, kognitief-affektiewe prosessering en neurobiologie is geëvalueer met standaard statistiese metodes. Die hoofbevindinge het op die volgende gedui: 1. swanger vroue het betekenisvolle hoër trait angs-vlakke getoon in trimester 2, vergeleke met trimester 1; 2. vergeleke met nie-swanger vroue, het swanger vroue beduidend meer aandag geskenk aan angstige gesigsuitdrukkings tydens elke trimester wat mag dui op veranderde kognitief-affektiewe prosessering tydens swangerskap vergeleke met nie-swangerskap; 3. swanger vroue het beduidend hoër PFK aktivering getoon teenoor angstige en kwaai gesigte in alle trimesters, maar veral in trimester 2; 4. swanger vroue se PFK aktivering het, in alle trimesters, beduidend gekorreleer het met stres-vlakke en selektiewe aandag teenoor bedreigende stimuli; en 5. swanger vroue se PFK aktivering het, in alle trimesters, ook 'n beduidende verwantskap getoon met verhoogde gluko-kortikoïed en geslagshormoonvlakke. Die hoofbevindinge in hierdie studie stem ooreen met vorige literatuur wat aangedui het dat daar 'n verband is tussen stres en veranderinge in kognitief-affektiewe prosessering en in prefrontale korteks aktivering, maar dui verder op veranderinge in emosionele regulering tydens swangerskap vergeleke met nie-swangerskap. Die data bied 'n belangrike insig in stres-veroorsakende sielkundige simptome; hul verwantskap met kognitief-affektiewe prosesse; veranderinge in neurologiese netwerke; en veranderinge in hormoonvlakke tydens swangerskap. Sover bekend is dit ook die eerste keer bevind dat strukture wat betrokke is by emosionele prosessering (bv. die PFK), ook betrokke is in die regulering van emosie tydens swangerskap. Dit is belangrik dat toekomstige navorsing die onderliggende meganismes wat veranderinge in emosionele regulering teweeg bring, ondersoek. Verdere ondersoek om hierdie veranderinge in swanger depressie-lyers of diegene met angssteurings te vergelyk is ook van belang.

Thesis (PhD (Psychiatry))--University of Stellenbosch, 2011. / ENGLISH ABSTRACT: Contemporary research has confirmed the presence of cognitive deficits as a core feature of schizophrenia that has a definite and adverse impact on functional outcome. Cognitive functioning can be improved by psychopharmacological intervention, with evidence supporting the superiority of second generation antipsychotics over their first generation predecessors. Despite evidence that cognitive impairment contributes to medication non-adherence and that depot antipsychotics are able to enhance treatment compliance whilst decreasing relapse rates, depot preparations remain less frequently prescribed than their oral counterparts, especially in patients with first episode psychosis (FEP). The aims of this study were primarily to investigate cognitive deficits in patients with FEP, and to then describe the response of these impairments to treatment with a very low dose flupenthixol decanoate. This was a prospective, non-randomized, single arm, open-label, longitudinal study of 58 participants with FEP treated according to a fixed protocol over a period of 12 months. There was a wash-out phase of up to seven days during which all psychotropic medications were discontinued. There was an initial treatment period of one week with oral flupenthixol 1mg/day, after which flupenthixol decanoate was initiated at 10mg intramuscular depot injection every fortnight. Dose increases, in cases of poor or inadequate response, were allowed at 6-weekly intervals and in increments of 10mg per injection, up to a maximum of 30mg per fortnight. The principal findings of the study were as follows: The majority of participants were markedly ill, with significant cognitive impairment at baseline. There was a discrepancy between subjectively reported, and objectively measured, cognitive impairment. The majority of the participants responded to, and achieved remission, on a very low dose of flupenthixol decanoate (22.48 ± 0.47mg/month). The majority of symptomatic and cognitive improvement occurred between baseline and three months, with response leveling out at six months. Social cognition did not improve significantly over time, whereas functional outcome and quality of life did improve with treatment. Flupenthixol decanoate was well tolerated and side-effects were of a mild and transient nature. This study reconfirms that the majority of individuals with FEP experience significant cognitive impairment at baseline. It also suggests that these impairments can be successfully treated with a very low dose of flupenthixol decanoate. The use of depot flupenthixol decanoate ensures sustained treatment delivery, thereby decreasing the risk for relapse. This holds the promise of improved long-term functional outcome for those suffering with psychotic illness. / AFRIKAANSE OPSOMMING: Onlangse navorsing het kognitiewe inkorting identifiseer as een van die kern simptoomkomplekse van skisofrenie, met toenemende bewyse vir die duidelike en ongunstige impak hiervan op funksionele uitkoms. Kognitiewe funksionering kan deur psigofarmakologiese ingrepe verbeter word. Onlangse literatuur toon dat die tweede generasie antipsigotika relatief meer effektief is as hulle eerste generasie voorgangers. Ondanks bewyse vir die negatiewe impak van kognitiewe inkorting op behandelingsinskiklikheid, én data wat daarop wys dat die gebruik van langwerkende intramuskulere (depot) antipsigotika inskiklikheid verbeter en periodes van simptoom-terugval voorkom, word dié preparate steeds minder gereeld as hulle orale eweknieë voorgeskryf, veral by pasiënte met 'n eerste episode psigose (FEP). Die doel van hierdie studie was om kognitiewe probleme by pasiënte met FEP te beskryf, en ook om die respons hiervan op behandeling met 'n baie lae dosis flupentiksol dekanoaat, te ondersoek. Die studie was 'n prospektiewe, nie-ewekansige, enkel middel, oop studie van 58 deelnemers met FEP, wat oor „n tydperk van 12 maande volgens 'n spesifieke protokol behandel is. Daar was 'n uitwas periode van 7 dae, waartydens alle psigotrope medikasie gestaak is. Hierna is behandeling met orale flupentiksol 1mg/dag begin vir een week, waarna flupentiksol dekanoaat geinisieer is teen 10mg intramuskulêr elke 2de week. Dosisverhogings, in geval van onvoldoende respons, was toelaatbaar met 6-weeklikse tussenposes, in inkremente van 10mg per inspuiting, tot 'n maksimum van 30mg elke 2de week. Die vernaamste bevindinge van die studie was soos volg: Die meerderheid van die deelnemers was ernstig siek, met beduidende kognitiewe inkorting tydens basislyn evaluasie. Daar was 'n verskil tussen subjektief-gerapporteerde en objektief-meetbare kognitiewe inkorting. Die meerderheid van die deelnemers het goed reageer op behandeling en het ook remissie op 'n baie lae dosis flupentiksol dekanoaat (22.48 ± 0.47mg/maand), bereik. Die meerderheid van simptomatiese en kognitiewe verbetering het plaasgevind binne die eerste 3 maande, met afplatting in die tempo en hoeveelheid van verbetering vanaf 6 maande. Sosiale kognisie het nie beduidend gedurende die studieperiode verbeter nie. Funksionele uitkoms en lewenskwailiteit van deelnemers het ook met behandeling verbeter. Flupentiksol dekanoaat is goed verdra en die newe-effekte, indien dit teenwoordig was, was van ligte graad en verbygaande aard. Hierdie studie herbevestig dat individue met FEP beduidende kognitiewe inkorting by basislyn ervaar, maar dat hierdie inkortings effektief met 'n baie lae dosis van flupentiksol dekanoaat behandel kan word. Die gebruik van depot flupentiksol is 'n suksesvolle manier om volgehoue behandeling te verseker en sodoende die risiko vir terugvalle te verminder. Dit verstewig dus die hoop op beter langtermyn funksionering vir persone met psigotiese siektes.