Doctorat en sciences psychologiques / info:eu-repo/semantics/nonPublished

A delayed, differential, classical conditioning paradigm was used to investigate defense and reward conditioning of autonomic responses in psychopaths. The CSs were tones and the UCSs were shock and pictures of nudes. The Ss were drawn from the inmate population of a maximum security penitentiary and were classified as primary psychopaths (P), secondary psychopaths (S), and nonpsychopaths (NP), according to criteria proposed by Cleckley and Karpman. The three dependent variables of chief interest, the GSR, HR, and finger vasoconstriction, were recorded simultaneously on an Offner Type R Dynograph. Differential conditioning was expressed as the amplitude of response to a reinforced CS minus the amplitude of response to the unreinforced CS. The primary hypothesis of the study was that Group P would show less defense conditioning of electrodermal, cardiac, and vasomotor responses than would Group NP. The secondary hypothesis predicted no significant differences between Groups P and NP in amount of reward conditioning on any of the autonomic measures investigated. The results showed that of the three physiological systems studied only the electrodermal differentiated between Groups P and NP with Group P; (1) showing significantly less defense conditioning; (2) giving smaller conditioned ORs, and smaller UCRs to shock; and (3) having a significantly lower level of basal skin conductance midway through the experiment. There was no significant difference between the two groups in reward conditioning although the tendency was for Group P to give ORs and ARs of smaller amplitude than those given by Group NP. No significant difference was found between groups in shock detection threshold or shock tolerance level - hence these variables were ruled out as significant contributors to the difference in defense conditioning. It was also shown that a difference in basal conductance between Groups P and NP was not significantly related to the observed difference in conditioning. Under both defense and reward stimulus conditions all groups showed evidence of conditioned HR deceleration, and an increase in the amplitude of vasomotor responses. There was no significant difference between Groups P and NP on any index of either cardiac or vasomotor activity. The GSR findings pertaining to defense conditioning were interpreted as providing additional evidence that primary psychopaths are deficient in the acquisition of conditioned fear responses. The reward conditioning results indicate that there is still no evidence that primary psychopaths differ from nonpsychopaths in the conditioning of reward responses. The difference between the amount of electrodermal and cardiovascular conditioning shown by Group P was related to structural and functional differences between the physiological systems investigated. The results of this study seem to permit the following tentative conclusions: (1) The GSR may be a more appropriate autonomic correlate of the psychopath's emotional reactivity than is either HR or finger vasoconstriction. (2) The primary psychopath's autonomic conditioning deficit may be restricted to the GSR. (3) In comparison with nonpsychopaths primary psychopaths are deficient in the acquisition of classically conditioned fear responses expressed as electrodermal measures. (4) There is no evidence that primary psychopaths and non-psychopaths differ significantly in the acquisition of classically conditioned reward responses. (5) Relative to nonpsychopaths primary psychopaths appear to be electrodermally hyporeactive. / Arts, Faculty of / Psychology, Department of / Graduate

Psychopathy is a complex personality disorder denned by a constellation of affective and behavioral characteristics. There is accumulating behavioral evidence suggesting that the condition is associated with impairments in affective, cognitive, and language functions. However, relatively little is known regarding the neural systems underlying these abnormalities. The present thesis is comprised of five experiments designed to elucidate and characterize the abnormal functional architecture underlying these abnormalities in psychopathic criminals. In Experiments 1 and 2, functional magnetic resonance imaging (fMRI) was used to elucidate the neural systems underling abnormal semantic and affective processes in these individuals. In Experiments 3, 4 and 5, event-related potentials (ERPs) were used to characterize the temporal features of cognitive and language functions in psychopaths. The results from Experiment 1 revealed that compared to control participants, psychopaths performed more poorly and failed to showed the appropriate neural differentiation between abstract and concrete stimuli during a lexical decision task. These deficits were located in the right anterior superior temporal gyrus. The results from Experiment 2 indicated that psychopaths, relative to control participants, showed less activation for processing affective stimuli than for neutral stimuli in several neural regions, including the right amygdala/hippocampal formation, left parahippocampal gyrus, ventral striatum, and in the anterior and posterior cingulate. Psychopaths did show greater activation for processing affective than for neutral stimuli in regions located outside the limbic system, including bilateral inferior frontal gyrus. These latter data suggesting that psychopaths used different neural systems than did controls for performing the task. The results from Experiments 3 and 4 indicated that psychopathy is associated with abnormalities in the P3 ERP component elicited by target stimuli during visual and auditory oddball tasks. In addition, the psychopaths' ERPs to visual and auditory target stimuli were characterized by large fronto-central negativities in the 350-600 millisecond time window. These fronto-central ERP negativities are similar to those observed for patients with temporal lobe damage. In Experiment 5, using a standard sentence processing paradigm, no group differences were observed between psychopaths and nonpsychopaths in the amplitude of the N400 potential elicited by terminal words of sentences that were either congruent or incongruent with the previous sentence context. These results indicate that the abnormal fronto-central ERP negativities observed in previous studies of language function in psychopaths are not related to processes involved in the generation of the N400. Taken together, these data suggest that one of the cardinal abnormalities in psychopathy is abnormal semantic processing of conceptually abstract information and affective information and that these abnormalities are related to the function of neural circuits in the anterior temporal lobes and lateral frontal cortex. / Arts, Faculty of / Psychology, Department of / Graduate

Cognitive impairments are a hallmark of many, if not all, psychiatric disorders. They include deficits in working memory, attention, and cognitive flexibility. The prefrontal cortex (PFC) is essential for these cognitive functions and has been implicated in psychiatric disorders, including schizophrenia. The PFC receives reciprocal inputs from the thalamus, and this thalamo-PFC circuitry supports cognition. In patients with schizophrenia, who have impaired cognitive functioning, thalamo-PFC connectivity is disrupted. This finding is also seen in adolescents at high risk for the disorder, even before diagnosis.While impaired cortical maturation has been postulated as a mechanism in the etiology of schizophrenia, the postnatal development of thalamo-PFC circuitry is still poorly understood. In sensory cortex, activity relayed by the thalamus during a postnatal sensitive period is essential for proper cortical maturation. However, whether thalamic activity also shapes maturation of the PFC is unknown. Here, I will present evidence to support the hypothesis that adolescence represents a sensitive period, during which the PFC is susceptible to transient perturbations in thalamic input activity, resulting in persistent changes in circuitry. In Chapter 1, I present the existing literature on schizophrenia and our current understanding of its etiology. I then review the structure and connectivity of the PFC and its inputs, including the thalamus, in the context of schizophrenia and cognition. Next, I discuss the role of adolescence in the development of these structures and circuits. Finally, I introduce the concept of sensitive periods and outline the hypothesis that a similar process may occur in the context of the adolescent development of thalamo-PFC circuitry. To assess cognitive functioning in mouse models, I developed an operant-based working memory task. In Chapter 2, I describe this newly developed task and demonstrate that behavioral performance in the task is susceptible to PFC lesions. Thus, the task offers a new approach to studying PFC cognitive function. In Chapter 3, I discuss work done to address the hypothesis of adolescence as a sensitive period in the development of thalamo-PFC circuitry. I established an approach whereby I can transiently reduce activity in the thalamus during specific time windows. In this way, I compared the persistent effects of transient thalamic inhibition during adolescence and adulthood. I found that adolescent thalamic inhibition causes long-lasting deficits in cognitive behavioral performance, including the operant-based working memory task described in Chapter 2 and a cognitive flexibility task, decreased PFC cellular excitability, and reduced thalamo-PFC projection density. Meanwhile, adult thalamic inhibition has no persistent consequences on behavior or PFC excitability. Adolescent thalamic inhibition also results in disrupted PFC cellular cross-correlations and task outcome encoding during the cognitive flexibility task. Strikingly, exciting the thalamus in adulthood during the behavioral task rescues PFC cross-correlations, task outcome encoding, and the cognitive deficit. These data support the hypothesis that adolescence is a sensitive period in thalamo-PFC circuit maturation as adolescent thalamic inhibition has long-lasting consequences on PFC circuitry, while adult thalamic inhibition has no persistent effects. Moreover, these results highlight the role of the thalamus as a non-specific facilitator of PFC activity, expanding our understanding of this thalamic function to additional cognitive contexts. By supporting PFC network activity, boosting thalamic activity provides a potential therapeutic strategy for rescuing cognitive deficits in neurodevelopmental disorders. Finally, in Chapter 4, I conclude with a general discussion. I highlight major take-aways from this work as well as next steps in our exploration of these crucial neural circuits. Together, the findings outlined here offer new promise for early diagnosis and treatment options for patients with cognitive impairments and psychiatric disorders.

Mental illness has been a perplexing mystery for centuries, inciting both fear and stigmatization. Yet, the knowledge that the brain gives rise to the mind transformed the field of psychiatry; biological studies of aberrant human behavior has revealed that mental disorders are rooted in physical abnormalities that may be targeted to alleviate symptoms. Even with recent progress, there remains many open questions, one of which is: how exactly are some individuals more susceptible to developing these disorders than others? Excess, or traumatic, stress can lead to the onset of maladaptive disorders such as major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). But what if it were possible to prevent these diseases from occurring in the first place? What if there was a prophylactic or vaccine-like approach to increase resilience against environmental stressors? Would we be able to target susceptible populations and administer this prophylactic? In this thesis, I present our work demonstrating the potential for prophylactic pharmaceuticals to enhance stress resilience and protect against stress-induced psychopathology. (R,S)-ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been demonstrated to be a viable candidate drug to administer as a prophylactic against stress-induced psychopathology. It was serendipitously discovered to rapidly (in as little as a half hour) and persistently (up to 2 weeks) alleviate depressive symptoms in patients with MDD. Since its discovery as an effective antidepressant, research has been focused on its mechanism of action with the goal of ultimately developing more efficacious, rapid-acting, long-lasting antidepressant drugs. However, in our lab, we made a truly unexpected discovery in 2016, described in Chapter 2: (R,S)-ketamine prevents the development of psychiatric symptoms when administered before a stressor. We found that prophylactic (R,S)-ketamine is effective against behavioral despair and buffers against learned fear in a time- and dose-specific manner, described in Chapter 3. This was the first indication that a drug can be administered before stress to prevent stress-induced psychopathology, opening a novel field of preventative psychopharmaceuticals. Follow-up studies in our and other labs have consistently replicated this effect using different stressors and mouse strains, in rats, and in both males and females. These data demonstrate that (R,S)-ketamine can effectively enhance resilience pre-clinically. To address how (R,S)-ketamine is inducing long-lasting protection, in Chapter 4, I describe a study that used a metabolomics platform to uncover the long-term effects of (R,S)-ketamine in buffering against learned fear. We found that (R,S)-ketamine alters purine and pyrimidine metabolism in brain and, most notably, the periphery. These data suggest the potential to conduct a simple blood test to screen for biomarkers of prophylactic efficacy in the clinic. However, while these data revealed the end-products of therapeutic efficacy, it was unknown what brain mechanisms may mediate such long-lasting protection against a psychological stressor. In a separate study, the ventral CA3 (vCA3) region of the hippocampus was uncovered to be necessary for (R,S)-ketamine’s prophylactic fear buffering effects, and that targeting this region both mimics and occludes its effects. It was then discovered that 1 week after a single administration of (R,S)-ketamine or FENM, AMPA bursts were attenuated in vCA3. These data reveal vCA3 a central node for prophylactic (R,S)-ketamine efficacy. The biggest limitation of these preliminary studies is that they each only assessed changes at single timepoints rather than mapped out what occurs throughout treatment, during stress, and during recall of a stressor. It remained unknown whether (R,S)-ketamine alters the experience or recollection of a stressor to induce long-lasting protection. The next goal was to use in vivo technologies such as 1-photon Ca2+ imaging in freely-moving mice to develop a more thorough understanding of how exactly (R,S)-ketamine is acting on vCA3 to confer its prophylactic fear buffering effects, which is outlined in Chapter 5. Mice were imaged in the ventral hippocampus throughout a prophylactic (R,S)-ketamine administration paradigm. We found that prophylactic (R,S)-ketamine administration buffered against the experience of the stressor specifically in vCA3 and reduced ventral hippocampal correlated network activity to ultimately buffer against learned fear. These data indicate that (R,S)-ketamine actively buffers against learned fear in the ventral hippocampal at the time of stress. The promise of (R,S)-ketamine is that it is also beneficial as a prophylactic in other settings beyond MDD and PTSD, such as in patients with traumatic brain injury (TBI). In Chapter 6, I describe a study that sought to determine whether (R,S)-ketamine can be useful as a prophylactic for TBI-induced neuropsychiatric effects. Here, TBI mice developed fear generalization, or the inability to distinguish between fear-inducing and neutral stimuli. To understand how TBI alters fear memory traces to promote fear generalization, we used the ArcCreERT2 x enhanced yellow fluorescent protein (eYFP) activity-dependent memory tagging strategy developed by Dr. Christine Ann Denny and found that TBI-induced fear generalization is partially mediated by dentate gyrus (DG) memory trace dysregulation. To reverse this fear generalization phenotype, a single administration of (R,S)-ketamine 1 hour after a TBI prevented the fear generalization phenotype. These data reveal the possibility of administering (R,S)-ketamine or other prophylactics in the clinic as part of post-operative care for TBI patients to prevent long-term fear generalization deficits. Altogether, this thesis demonstrates the potential for pharmacotherapies for stress resilience enhancement and reveals potential targets for prophylactic drug development. We have uncovered the long-term metabolomic changes that occur after a single dose of (R,S)-ketamine, revealed a central node for prophylactic efficacy, mapped the dynamic changes that occur throughout treatment, and applied the prophylactic paradigm to a model of TBI to demonstrate the broad range of applications of this approach. This work paves the way for the novel field of preventative psychiatry and opens new avenues to explore ways to reduce the devastating impact of mental illness on individuals and society.

Text in Afrikaans / The purpose of this study was to determine the nature, origin and negative consequences of perfectionism and to set guidelines for the therapeutic handling of perfectionism. Two literature studies were done to investigate the phenomenon and therapeutic techniques with regards to perfectionsim. A questionnaire was developed as aid to the therapist to identify negative perfectionism and associated problem areas. An empirical study was done to investigate the effectivity of the questionnaire and to compose a program and guidelines for the therapist and perfectionist. Results of the study indicated that negative perfectionism resulted in affective, cognitive, interpersonal and behavioural consequences for the client. It further showed that it is necessary to find the origin of the client's perfectionism and to give them insight in their problem to enable the therapist to succesfully apply cognitive behavioral therapy. / Educational Studies / M. Ed. (Voorligting)

Dissertation (DSc)-- Stellenbosch University, 2008. / ENGLISH ABSTRACT: The overall aim of these studies was to investigate selected aspects of psychopathology, neurobiological abnormalities and treatment in schizophrenia. The following topics were researched: 1. Psychopathology: We explored the symptom structure of schizophrenia by means of principal components and factor analysis in two separate samples. a. The first study investigated the nature of symptoms in patients with a first-episode of schizophrenia, in a large cohort of patients who were participating in a multinational clinical trial. We compared our findings with similar analyses previously conducted in multi-episode schizophrenia patients. b. We then assessed the influence of culture on the symptom structure of schizophrenia by conducting a principal components and factor analysis of the symptom ratings in a large sample of South African Xhosa patients with schizophrenia, and comparing the results with those in other parts of the world. c. We investigated the occurrence of co-morbid depressive and anxiety symptoms, and their demographic and clinical correlates. The sample for this study comprised acutely psychotic patients who were participants in clinical drug trials conducted at our centre. d. To explore the relationships between obsessive-compulsive disorder and schizophrenia, we conducted a review of the relevant literature. 2. Neurobiological abnormalities: a. We performed a series of studies to investigate disorders of water homeostasis and vasopressin secretion in schizophrenia. To test the hypothesis that acutely psychotic patients have disordered regulation of water homeostasis, we applied a dynamic suppression test - a water loading test, with assessment of excretory capacity (including arginine vasopressin assay) in acutely psychotic patients. To evaluate whether a subset of patients with schizophrenia and co-morbid disordered water homeostasis sustained cerebral damage as a consequence of water intoxication we did the following experiment: We identified a cohort of subjects with schizophrenia and disordered water homeostasis and compared them with patients with schizophrenia without disordered water homeostasis in terms of cerebral ventricular size and cognitive function. To assess the prevalence of disordered water homeostasis in a long-term inpatient sample of psychiatric patients we conducted serum sodium screening tests. Those subjects with dilutional hyponatraemia were then further investigated for dysregulation of water homeostatic mechanisms. b. We studied neurological soft signs in a sample of subjects with first-episode schizophrenia followed up over a two year period. We investigated their occurrence, relationships to psychiatric symptoms and medication effects, their temporal stability and their outcome correlates. We also investigated their potential to predict outcome in schizophrenia 3. Treatment aspects A great deal of our work has focussed on the pharmacological treatment of schizophrenia. The following aspects of treatment are included in this thesis: a. Treatment effects on psychiatric symptoms: i. To assess the effects of ethnicity on treatment outcome in schizophrenia we compared the acute response to antipsychotic treatment in 3 ethnic groups, namely blacks, coloureds and whites. We included patients in this analysis who had participated in clinical trials in our department as well as the Department of Psychiatry in the University of the Free Sate. Patients had been treated under blinded conditions over a 6-week period. ii. After discussions with the late Dr David Horrobin, who had pioneered possible applications of the omega-3 fatty acids in the treatment of various psychiatric disorders, we became interested in further investigating the potential of this group of compounds as an affordable adjunct to treating schizophrenia. We assessed the antipsychotic potential of the omega-3 fatty acid, ethyl-eicosapentaenoic-acid (e-EPA) supplementation versus placebo supplementation in a small sample of subjects with schizophrenia who had been only partially responsive to antipsychotic treatment previously. We also conducted a review of the literature to evaluate the evidence for efficacy for the omega-3 fatty acids in schizophrenia according to published studies. b. Treatment effects on neurological abnormalities: i. In a single-blinded controlled study we compared a new generation antipsychotic to a conventional antipsychotic in the treatment of tardive dyskinesia (TD). This was a long-term (1 yr) study in patients with chronic schizophrenia and established tardive dyskinesia. ii. We also assessed the effect of omega-3 fatty acid (e-EPA) supplementation in treating TD. This was conducted in a larger sample (n=84) of patients with chronic schizophrenia and established TD. The blinded, placebo-controlled phase was 12 weeks. This was followed by an open-label extension for 40 weeks. c. Conventional versus new generation antipsychotic agents. Several evidence-based literature reviews of the efficacy and tolerability of the new generation of antipsychotics compared to the conventional agents were conducted. Some multinational, randomised, controlled clinical trials in which the author was principal investigator, are included in this thesis. Also, studies addressing patients with partial treatment refractoriness are included, as well as studies of the effects of antipsychotics on depressive symptoms, body mass and glycaemic control. Finally, we have included a pharmacoeconomic study comparing a conventional antipsychotic (haloperidol) with a new generation antipsychotic (quetiapine) in partially refractory patients in a South African setting. Findings and conclusions: 1. Psychopathology: Our studies demonstrated that the factor structure for the symptoms of schizophrenia is replicable across samples, and is not greatly influenced by ethnic and cultural factors. However, changes in the factor structures do occur over time. There are symptom domains that are present in first-episode schizophrenia but disappear as a distinct entity as the illness becomes chronic. Particularly, a motor component is evident in untreated patients, but disappears after initiation of treatment. We found that depression and anxiety are common co-morbid symptoms in schizophrenia, and have important clinical and outcome correlates. Depressive symptoms in the acute psychotic phase of schizophrenia are associated with a favourable prognosis and diminish as the symptoms of psychosis improve in response to antipsychotic treatment. However, persistent depressive symptoms are associated with a poorer prognosis, and require additional therapeutic intervention. 2. Neurobiological abnormalities: We investigated the occurrence of disordered water regulation in a population of psychiatric inpatients, and conducted further investigations on those identified, in order to establish mechanisms involved. Polydipsia and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) were found to occur in a subset of patients with schizophrenia, and are associated with acute psychosis, as well as with some psychotropic medications. These patients are characterised by more severe cognitive impairment and evidence of cerebral atrophy. The condition can become life-threatening in the presence of other factors impeding water excretion, particularly thiazide diuretics. Neurological soft signs were investigated in a sample of patients with a first-episode of schizophrenia. These soft signs appear to be trait-like (present early in the illness, and stable over time), except for a motor sequencing factor. Patients performing poorly on this latter group of tests have a longer duration of untreated psychosis, and are at significant risk for developing TD. 3. Treatment aspects: Our studies suggest that there are important ethnic differences in antipsychotic treatment response, but that these differences could be explained by a number of environmental and biological factors. As was found with many studies worldwide, we found that the new generation antipsychotics have important efficacy and safety advantages over their predecessors. Risperidone was as effective as haloperidol in first-episode psychosis, but with a more favourable side-effect profile in terms of reduced extrapyramidal symptoms. Quetiapine treatment in partially refractory patients resulted in more responders compared to haloperidol, and fewer extrapyramidal symptoms. However, evidence of a different side-effect profile is emerging. Of particular concern is the finding that some of the new antispychotics cause weight gain, glucose intolerance and dyslipidaemias. We found that one novel antipsychotic, quetiapine, was not associated with significantly more weight gain or disordered glucose metabolism that a conventional agent, haloperidol. The omega-3 fatty acids, particularly EPA may have a role in the treatment of various psychiatric disorders. Our studies provided mixed results – the first found a significant beneficial effect on psychotic symptoms and dyskinesia scores for EPA supplementation, while the second failed to demonstrate a beneficial effect on TD or psychotic symptoms. We explored the early treatment response in first-episode psychosis and found, unlike that reported in multi-episode patients, some patients took a long time to respond. We also found that early treatment response was a significant predictor of later remission, as was duration of untreated psychosis, educational level and baseline excitement factor scores. Finally, our pharmacoeconomic study conducted for South African circumstances in patients with a partial response to conventional antipsychotic treatment showed cost-neutrality or cost-benefits for quetiapine compared with haloperidol treatment for direct costs. / AFRIKAANSE OPSOMMING: Die oorkoepelende doel van hierdie studies was om geselekteerde aspekte van psigopatologie, neurobiologiese abnormaliteite en behandeling in skisofrenie te ondersoek. Die volgende onderwerpe is nagevors: 4. Psigopatologie: Ons het die simptoomstruktuur van skisofrenie ondersoek deur middel van hoofkomponent- en faktoranalise in twee aparte steekproewe. a. Die eerste studie het die aard van simptome in pasiënte, met ʼn eerste-episode van skisofrenie, ondersoek in ʼn groot kohort van pasiënte wat deelgeneem het aan ʼn multi-nasionale kliniese proefneming. Ons het ons bevindinge vergelyk met soortgelyke analises wat voorheen gedoen is in multi-eposode skisofrenie pasiënte. b. Hierna het ons die invloed van kultuur op die simptoom struktuur van skisofrenie geassesseer deur ʼn hoofkomponent- en faktoranalise van die simptoomtellings uit te voer in ʼn groot steekproef van Suid-Afrikaanse Xhosa pasiënte met skisofrenie en die resultate te vergelyk met bevindinge in ander dele van die wêreld. c. Ons het die voorkoms van ko-morbiede depressiewe en angssimptome ondersoek, asook hul demografiese en kliniese korrelate. Die steekproef vir hierdie studie het bestaan uit akute psigotiese pasiënte wat deelnemers was in ʼn kliniese geneesmiddel proef wat uitgevoer is by ons sentrum. d. Om die verband tussen obsessief-kompulsiewe steurnis en skisofrenie te verken, het ons ʼn oorsig van die relevante literatuur gedoen. 5. Neurobiologiese abnormaliteite: a. Ons het ʼn reeks studies uitgevoer om steurnisse in water homeostase en vasopressien sekresie in skisofrenie te ondersoek. Om die hipotese dat akute psigotiese pasiënte versteurde regulering van water homeostase het te ondersoek, het ons ʼn dinamiese onderdrukkingstoets toegepas – ʼn water ladingstoets, met assessering van ekskresiekapasiteit (insluitend arginien vasopressien essai) in akute psigotiese pasiënte. Om te evalueer of ʼn onderafdeling van skisofrenie pasiënte met ko-morbiede versteurde water homeostase serebrale skade opgedoen het as gevolg van water intoksikasie, het ons die volgende eksperiment uitgevoer: Ons het ʼn kohort deelnemers met skisofrenie en versteurde water homeostase geïdentifiseer en hulle vergelyk met skisofrenie pasiënte sonder versteurde water homeostase in terme van serebrale ventrikulêre grootte en kognitiewe funksionering. Om die voorkoms van versteurde water homeostase in ʼn langtermyn binne-pasiënt steekproef van psigiatriese pasiënte te bepaal, het ons serum natrium siftingstoetse uitgevoer. Deelnemers met hiponatremie is hierna verder ondersoek vir disregulering van water homeostatiese meganismes. b. Ons het neurologiese sagte tekens in ʼn steekproef van deelnemers met eersteepisode skisofrenie bestudeer en opgevolg oor ʼn twee jaar tydperk. Ons het hulle voorkoms, verwantskappe met psigiatriese simptome en medikasie effekte, hulle temporale stabiliteit en hul uitkoms korrelate ondersoek. Ons het ook hulle potensiaal om die uitkoms in skisofrenie te voorspel, ondersoek. 6. Behandelings aspekte ʼn Groot meerderheid van ons werk het gefokus op die farmakologiese behandeling van skisofrenie. Die volgende aspekte van behandeling is ingesluit in hierdie tesis: a. Behandelingseffekte op psigiatriese simptome: i. Om die effek van etnisiteit op behandelingsuitkoms in skisofrenie te assesseer, het ons die akute respons op anti-psigotiese behandeling in 3 etniese groepe vergelyk, naamlik swart, gekleurd, en wit. Ons het pasiënte wat deelgeneem het aan kliniese proefnemings in ons departement sowel as die Departement Psigiatrie van die Universiteit van die Vrystaan ingesluit in hierdie analise. Pasiënte is behadel onder geblinde toestande oor ʼn tydperk van 6 weke. ii. Na besprekings met wyle Dr David Horrobin, wie die moontlike toepassings van omega-3 vetsure in die behandeling van verskeie psigiatreise steurnisse gepionier het, het ons begin belangstel in verdere ondersoek na die potensiaal van hierdie groep samestellings as ʼn bekostigbare toevoeging in die behandeling van skisofrenie. Ons het die anti-psigotiese potensiaal van die omega-3 vetsuur, etieleikosapentanoësuur (e-EPA) supplementasie versus plasebo supplementasie ondersoek in ʼn klein steekproef van deelnemers met skisofrenie wat slegs gedeeltelik responsief was op anti-psigotiese behandeling in die verlede. Ons het ook ʼn literatuuroorsig gedoen om die bewyse vir die effektiwiteit vir die omega-3 vetsure in skisofrenie te evalueer volgens gepubliseerde studies. b. Behandelingseffekte op neurologiese abnormaliteite: i. In ʼn enkelblinde kontrole studie het ons ʼn nuwe generasie anti-psigotiese medikasie vergelyk met ʼn konvensionele anti-psigotiese medikasie in die behandeling van tardiewe diskinesie (TD). Hierdie was ʼn langtermyn (1- jaar) studie in pasiënte met chroniese skisofrenie en vasgestelde TD. ii. Ons het ook die effek van omega-3 vetsuur (e-EPA) suplementasie geassesseer in die behandeling van TD. Dit was gedoen in ʼn groter steekproef (n=84) van pasiënte met chroniese skisofrenie en vasgestelde TD. Die blinde, placebo kontrole fase was 12 weke. Dit is gevolg deur ʼn nie-geblinde ekstensie vir 40 weke. c. Konvensionele versus nuwe generasie anti-psigotiese agente. Verskeie bewys-gebaseerde literatuuroorsigte oor die effektiwiteit en toleransie van die nuwe generasie anti-psigotiese agente in vergelyking met die konvensionele agente, is gedoen. Sommige multi-nasionale, ewekansige, kontole kliniese proefnemings waarin die outeur die hoofnavorser was, is ingesluit in hierdie tesis. Verder, studies wat die pasiënte met gedeeltelike behandelingsweerstandigheid aanspreek, is ingesluit, sowel as studies oor die effekte van anti-psigotiese agente op depressiewe simptome, liggaamsmassa en glisemiese kontrole. Laastens, het ons a farmakoekonomiese studie ingesluit wat die konvensionele anti-psigotiese behandeling (haloperidol) met ʼn nuwe generasie anti-psigotiese behandeling (quetiapien) in gedeeltelik weerstandige pasiënte in ʼn Suid-Afrikaanse ligging vergelyk. Bevindinge en gevolgtrekkings: 4. Psigopatologie: Ons studies het gedemonstreer dat die faktor struktuur vir die simptome van skisofrenie herhaalbaar is oor steekproewe, en dat dit nie grootliks beïnvloed word deur etnisiteit en kulturele faktore nie. Veranderinge vind egter in die faktor strukture wel plaas met verloop van tyd. Daar is simptoom domeine wat teenwoordig is in eerste-episode skisofrenie, maar verdwyn as ʼn afsonderlike entiteit soos wat die toestand chronies word. Spesifiek, ʼn motoriese komponent is duidelik in onbehandelde pasiënte, maar verdwyn na die aanvang van behandeling. Ons het gevind dat depressie en angs algemene ko-morbiede simptome in skisofrenie is en het belangrike kliniese en uitkoms korrelate. Depressiewe simptome in die akute psigotiese fase van skisofrenie word geassosieer met ʼn gunstige prognose en verminder soos wat die simptome van psigose verbeter in repons op anti-psigotiese behandeling. Egter, volgehoue depressiewe simptome word geassosieer met ʼn swakker prognose en benodig addisionele terepeutiese intervensie. 5. Neurobiologiese abnormaliteite: Ons het die voorkoms van versteurde water regulering ondersoek in ʼn populasie van psigiatriese binne-pasiënte en verdere ondersoek ingestel op dié wie geïdentifiseer is, om die betrokke meganismes vas te stel. Polidipsie en en die sindroom van onvoldoende antidiuretiese hormoon sekresie (SIADH) is gevind om voor te kom in ʼn onderafdeling van pasiënte met skisofrenie, en word geassosieer met akute psigose sowel as met somige psigotropiese medikasie. Hierdie pasiënte word gekenmerk deur meer ernstige kognitiewe beperking en bewyse van serebrale atrofie. Die toestand kan lewensbedreigend raak in die teenwoordigheid van ander faktore wat water ekskresie hinder, veral tiasied diuretikums. Neurologiese sagte tekens is ondersoek in ʼn steekproef van pasiënte met eerste-episode skisofrenie. Hierdie sagte tekens blyk om kenmerkend (teenwoordig vroeg in die siekte, en stabiel oor tyd) te wees, behalwe vir ʼn motoriese volgorde faktor. Pasiënte wat swak vaar op die laasgenoemde groep toetse, het ʼn langer durasie van onbehandelde psigose, en het ʼn beduidende risko om TD te ontwikkel. 6. Behandeling aspekte: Ons studies stel voor dat daar ʼn belangrigke etniese verskil is in anti-psigotiese behandelingsrespons, maar dat hierdie verskille verduidelik kan word deur ʼn aantal omgewings- en biologiese faktore. Soos wat gevind was vir verskeie studies wêreldwyd, het ons gevind dat die nuwe generasie anti-psigotiese agente belangrike effektiwiteit- en veiligheidsvoordele het bo hulle voorgangers. Risperidoon was net so effektief as haloperidol in eerste-episode psigose, maar met ʼn meer gunstige newe-effkte profiel in terme van verminderde ekstrapirimidale simptome. Quetiapien behandeling in veral refraktêre pasiënte het gelei tot meer respondeerders vergeleke met haloperidol, en minder ekstra pirimidale simptome. Alhoewel, bewyse van ʼn verskillende newe-effekte profiel is besig om na vore te kom. Van spesifieke belang is die bevinding dat sommige van die nuwe anti-psigotiese agente gewigstoename, glukose intoleransie en dyslipidemie veroorsaak. Ons het gevind dat een nuwe anti-psigotiese agent, quetiapien, nie geassosieer was met enige beduidende meer gewigstoename of versteurde glukose metabolisme as ʼn konvensionele agent, haloperidol, nie. Die omega-3 vetsure, spesifiek EPA mag moontlik ʼn rol in die behandeling van verskeie psigiatriese versteurings hê. Ons studies het gemengde resultate voorsien – die eerste het ʼn beduidende voordelige effek op psigotiese simptome en diskinesie tellings vir EPA supplementasie gevind, terwyl die tweede nie ʼn voordelige effek op TD of psigotiese simptome gevind het nie. Ons het die vroeë behandelingsrespons ondersoek in eersteepisode pasiënte en het gevind, in teenstelling met dit wat gerapporteer word in multi-episode pasiënte, dat sommige pasiënte ʼn lang tyd geneem het om te reaggeer. Ons het ook gevind dat vroeë behandelingsrespons ʼn beduidende voorspeller was van latere remissie, so ook die durasie van onbehandelde psigose, opvoedingspeil, en basisvlak opwindings-faktor tellings. Laastens het ons farma-ekonomiese studie, wat uitgevoer is vir Suid-Afrikaanse omstandighede in pasiënte met ʼn gedeeltelike repons op konvensionele anti-psigotiese behandeling, koste-neutraliteit of koste-voordele aangetoon vir quetiapien vergeleke met haloperidol behandeling vir direkte onkostes.

Thesis (PhD)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: Both chronic trauma and shame, as well as the relation between them, are understudied phenomena. This is despite particularly high levels of both trauma- and shame-related psychopathology in South Africa (Edwards, 2005). I conducted a qualitative study exploring experiences of trauma, shame, post-traumatic reactions and coping mechanisms in single interviews with 19 South African survivors of chronic trauma (intimate partner violence) using narrative analysis. Results from the categorical content analysis indicated that all but one participant reported a history of physical violence perpetrated by her intimate partner. Sexual and emotional violence were also reported by the majority of the participants. The most significant reported mental health outcomes were persistent fear, depression and suicidality, dissociation and somatic complaints. Coping mechanisms included religion, support from family, counselling and substance misuse. Using smiling as a mask to conceal difficult feelings and keeping occupied were cited as the most effective defenses. Shame was viewed as a social emotion, and often described as humiliation (and sometimes embarrassment), which required the presence of a mocking, hostile audience. This was interpreted in socio-cultural terms. Eleven women presented with a split self – the authentic self who admitted to a great deal of shame when asked indirectly, and the false self who was described in surprisingly positive terms. I analysed this split using categorical content analysis and narrative analysis from a social constructivist point of view at individual (clinical) level, organisational (micro-cultural) level, and broader cultural level. I used Gee’s (1991) categorical form analysis to analyse five long complex shame and trauma narratives with the aim of determining if psychic fragmentation presents at linguistic level. I also analysed three short, compressed trauma and shame narratives. The structure of the short narratives tended to be circular, erratic, disjointed, and interrupted (Scarry, 1985; Simon, 2008). The three short, compressed trauma narratives were characterised by long pauses or silences, hesitations, avoiding eye contact, hunching over, covering the face with clothes, whispering, so making the narrative almost inaudible, crying, and defensive leaning in towards me, and laughing. These women were exceptions – most women expressed an urgency to talk about their experiences in great detail. Although the longer narratives are essentially fractured chaos narratives at linguistic level, they contain predominant trauma- and shame-related themes that are consistent throughout the narratives and that remain intact in spite of the signs of linguistic disruption and fragmentation. They are, in order of narratives, 1) shame/self-blame and deservedness; 2) truth/lies and bearing witness; 3) shame, humiliation and dissociation; 4) the concealed, shame-based self, including amnesiac-like disorientation of place and time; and 5) patterns of cyclical leave-return reflecting perpetrator-instilled abandonment terror, including disorientation of time. I have argued that although language, or narrative structure, continues to mimic and reflect narrative content (fractured narratives vs fractured selves) – there is also the intriguing possibility of a disconnection between form and content; and that thematic coherence or consistency and narrative fracturing can co-occur; co-exist. There are a number of clinical features in the narratives which are either related to, or comprise diagnostic criteria for chronic trauma syndromes such as chronic PTSD and DESNOS, and intersect with shame themes in the narratives I analysed. Consequently, I argue that there is a substantial intersection or co-occurrence between exposure to chronic trauma, and trauma-related clinical symptoms, including shame, which emerge from the narratives, which without exception, demonstrate significant linguistic fracturing. In conclusion, a number of gaps in the literature were identified. Future research should triangulate methods and chronic trauma prevalence and longitudinal studies are needed both internationally and locally. / AFRIKAANSE OPSOMMING: Sowel kroniese trauma as skaamte, en die verhouding tussen die twee, is tot dusver onvoldoende bestudeer – ondanks die besonder algemene voorkoms van trauma- en skaamte-verwante psigopatologie in Suid-Afrika (Edwards, 2005). Ek het ʼn kwalitatiewe studie onderneem en die ervaring van trauma, skaamte, post-traumatiese reaksies en oorlewingsmeganismes ondersoek in indiwiduele onderhoude met 19 Suid-Afrikaanse oorlewendes van kroniese trauma (geweld in intieme verhoudings). In my ondersoek het ek van narratiewe analise gebruik gemaak. Resultate van die kategoriese inhoudsanalise dui aan dat ál die vroue in die bestudeerde groep, behalwe een, ‘n geskiedenis van fisieke geweld gerapporteer het wat deur haar ‘partner’ gepleeg is. Seksuele en emosionele geweld is ook deur die meerderheid van die groep gerapporteer. Die mees betekenisvolle uitkomste in verband met psigiese gesondheid was voortdurende angs, depressie, selfmoordneigings, dissosiasie en somatiese klagtes. Oorlewingsmeganismes was onder andere godsdiens, berading en dwelms. Om ʼn glimlag te gebruik as masker vir die verberging van pynlike emosies, en om besig te bly, is genoem as die effektiefste verdedigingsmeganismes. Skaamte is gesien as ‘n sosiale emosie, en is dikwels ‘vernedering’ genoem (soms ʼn ‘verleentheid’), wat die teenwoordigheid van spottende, vyandige toeskouers impliseer. Skaamte is in die studie in sosio-kulturele terme geïnterpreteer. Elf vroue het 'n gesplete self vertoon – die outentieke self wat 'n groot hoeveelheid skaamte erken het wanneer hulle indirek daaroor uitgevra is, teenoor die valse self wat in verbasend positiewe terme beskryf is. Ek het hierdie gesplete self geanaliseer met gebruikmaking van kategoriale inhoudsanalise en ook van narratiewe analise uit 'n sosiaal-konstruktiewe perspektief – op 'n indiwiduele (kliniese), organisatoriese (mikro-kulturele) en ‘n breër kulturele vlak. Ek het Gee (1991) se kategoriale vorm-analise gebruik om vyf lang, komplekse skaamte- en traumanarratiewe te analiseer om te bepaal of psigiese fragmentering op 'n linguistiese vlak manifesteer. Ek het ook drie kort, gedronge trauma- en skaamtenarratiewe geanaliseer. Die struktuur van die kort narratiewe was geneig om sirkulêr, wisselvallig, onsamehangend en onderbroke te wees (Scarry, 1985; Simon, 2008). Die drie kort, gedronge traumanarratiewe is gekenmerk deur lang stiltes, aarseling, vermyding van oogkontak, vooroor buk, bedekking van die gesig met klere, fluistering (sodat die narratief byna onhoorbaar geword het), gehuil, defensiewe oorleun na my toe, en gelag. Hierdie drie vroue was uitsonderings – die meeste vroue het 'n dringende behoefte laat blyk om in fyn besonderhede oor hulle ervarings te praat. Alhoewel die langer narratiewe op 'n linguistiese vlak wesentlik gefragmenteerde chaos-narratiewe is, bevat hulle dominante trauma- en skaamte-temas wat konsekwent deur die verhale aanwesig bly ondanks die tekens van linguistiese disrupsie en fragmentering. Hulle is, in die volgorde van die narratiewe, 1) skaamte/selfblamering en verdiende loon; 2) waarheid/leuens en getuienis aflê; 3) skaamte, vernedering en dissosiasie; 4) bedekte, skaamte-gebaseerde self, insluitend die amnesieagtige disoriëntering van plek en tyd; en 5) patrone van sikliese vertrek en terugkeer, insluitend 'n disoriëntering van plek en tyd – 'n refleksie van die vrees om alleen gelaat te word, veroorsaak deur die gewelddadige optrede teen haar. Ek het geredeneer dat, alhoewel taal/ narratiewe struktuur geneig is om narratiewe inhoud na te boots en te reflekteer (gefragmenteerde narratiewe naas gefragmenteerde self) – is daar ook die interessante moontlikheid van 'n diskonneksie tussen vorm en inhoud; en dat tematiese samehang of konsekwentheid saam met narratiewe fragmentering kan voorkom. Daar is 'n aantal kliniese kenmerke in die narratiewe wat diagnostiese kriteria bevat vir kroniese trauma-sindrome soos kroniese PTSD en DESNOS, en wat verband hou met skaamtetemas in die betrokke narratiewe. Gevolglik redeneer ek dat daar 'n substansiële oorvleueling of saambestaan is van die blootstelling aan kroniese trauma en trauma-verwante kliniese simptome, insluitend skaamte. Dit kom na vore in die geanaliseerde narratiewe, wat sonder uitsondering deur linguistiese fragmentering gekenmerk word. Ten slotte is ‘n aantal leemtes in die literatuur geïdentifiseer. Toekomstige navorsing behoort metodes en algemeen-voorkomende kroniese trauma te trianguleer en longitudinale studies, plaaslik en internasionaal, word benodig.

This study explored three areas believed to play a central role in the pathogenesis and presenting clinical picture of the eating disorders, anorexia nervosa and bulimia. Measures of personal effectiveness, family dynamics, and traditional sex-role beliefs were assessed in groups of restricted anorexics, bulimic anorexics, normal weight bulimics and controls. Control subjects manifested the highest degree of psychological adjustment, resourcefulness, and self-direction, while restricting anorexics obtained the lowest score on this measure. Bulimics experienced the highest degree of personal effectiveness of the patient groups, with bulimic anorexics falling in-between restricting anorexics and bulimics. Control subjects also reported that they felt more independent, accepted and tolerated in their family than any of the eating disorder groups. Bulimic subjects scored closest to controls on this measure, with bulimic anorexics experiencing the least degree of acceptance, tolerance and independence of all groups. Finally, control subjects defined themselves in a more traditionally masculine role than did any of the eating disorder groups. Restricting anorexics were most likely to describe themselves as passive, submissive, constricted and sensitive; bulimic subjects were more likely to endorse such self-descriptive adjectives as assertive, uninhibited, self-confident and competitive. Bulimic anorexics perceived themselves to be less traditionally feminine than did restricting anorexics, but more than bulimics or controls. The results of this study support the theory that ego deficits contribute to the development of eating disorders.

Understanding the relation between personality characteristics, psychopathology, and sexual offenses can contribute to developing more effective treatment interventions. Previous research with sex offenders has focused on general personality traits or inconsistently classified sex offenders based on psychopathology. It was hypothesized that combining personality and psychopathological traits can assist in understanding sex offenders. The current study evaluated 88 male sex offenders in a court-mandated outpatient treatment program utilizing the NEO-PI-R and the MMPI-2. Three clusters of child molesters were examined for differences in personality characteristics and number of offenses. A second-order principle axis factor (PAF) analysis of personality and psychopathology traits revealed three factors: Psychological Distress, Excitement-Seeking, and Social Desirability. The potential clinical utility of these dimensions in predicting treatment compliance is examined.