Doctoral Degrees (Psychiatry)

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The adaptation and norming of selected psychometric tests for 12- to 15- year-old urbanized Western Cape adolescents
(Stellenbosch : Stellenbosch University, 2011-12) Ferrett, Helen Louise; Carey, Paul; Thomas, K.; Stellenbosch University. Faculty of Health Sciences. Dept. of Psychiatry.
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.
An adapted intervention for problematic alcohol use in people living with AIDS and its impact on alcohol use, general functional ability, quality of life and adherence to HAART : a cluster randomized control trial at Opportunistic Infections Clinics in Zimbabwe
(Stellenbosch : Stellenbosch University, 2018-12) Madhombiro, Munyaradzi; Seedat, Soraya; Rusakaniko, Simba; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Psychiatry.
ENGLISH SUMMARY : With the advent of antiretroviral therapy, the HIV pandemic has become a chronic illness requiring lifelong treatment. The 90-90-90 strategy, adopted by UNAIDS, aims for (i) 90% of HIV infected persons knowing their status, (ii) 90% on antiretroviral therapy; and (iii) 90% achieving viral suppression. The goal is to reach these aims by 2020. Alcohol use affects the attainment of the 90-90-90 goals. Research shows that people living with HIV (PLWH) drink twice as much as their HIV negative counterparts. Alcohol use disorders (AUD) in PLWH are associated with poor adherence to ART. Recommendations have been made to include interventions for AUDs in HIV prevention and treatment strategies. Brief interventions are recommended for hazardous alcohol use; however, for alcohol dependence a stepped care model incorporating behavioural/psychological treatments and pharmacological interventions may be required. Pharmacological treatments may lead to a higher pill burden and psychological interventions are, therefore, the treatment of choice. Psychological interventions have traditionally been delivered by a highly skilled workforce. However, in low and medium income countries (LMIC) where the HIV prevalence is high, there is a shortage of a skilled workforce. Task sharing has been recommended as a way of scaling up the delivery of services. The aim of this study was to adapt an evidence-based intervention for HIV and AUDs in Zimbabwe and to assess its effectiveness in a cluster randomized controlled trial (RCT). To achieve this, we first conducted a systematic review of the evidence for the effectiveness of psychological interventions. Second, a qualitative study was done to understand knowledge and perceptions of AUDs among PLWH and potential barriers and facilitators of interventions for AUDs. Third, we conducted a pilot and feasibility study in preparation for the RCT. The systematic review found limited evidence for the effectiveness of psychological interventions for AUDs, particularly on the frequency of drinking. Motivational interviewing (MI) alone and in combination with mobile technology, and cognitive behavioural therapy (CBT) were found to be effective. Additionally, MI was effective in reducing risky sexual behaviour, adherence to ART, other substance use disorders, viral load reduction, and increase in CD4 count. The qualitative study found that PLWH had adequate knowledge of the direct and indirect effects of alcohol use on HIV transmission and adherence to treatment, and were concerned about the stigma faced by PLWH who have and AUDs. Furthermore, participants were concerned about the stigma faced by PLWH who have AUDs. They called for stigma reduction strategies to be implemented and were receptive of the idea of interventions for AUDs. Following a pilot study which indicated that an intervention for AUDs was feasible, a cluster RCT was carried out at 16 HIV care clinics. The adapted intervention included motivational interviewing blended with cognitive behavioural therapy (MI/CBT). The comparator intervention was the alcohol use section of the World Health Organisation (WHO) mental health Gap Action Program Intervention Guide (mh GAP IG). The MI/CBT and mh GAP IG interventions were delivered by registered general nurses (RGN) embedded in HIV care clinics. The primary outcome was a reduction in alcohol use as measured by the Alcohol Use Disorders Identification Test (AUDIT) score. Secondary outcome measures included: (i) HIV disease parameters, as measured by the viral load and CD4 count; (ii) functionality, as assessed by the WHO Disability Assessment Schedule (WHODAS 2.0); and (iii) quality of life, as measured by the WHO Quality of Life HIV (WHOQOL HIV). The cluster RCT demonstrated that RGNs can be trained to deliver an MI/CBT intervention for AUDs in PLWH. Additionally, the MI/CBT intervention significantly reduced alcohol consumption in PLWH. While the reduction in alcohol consumption was maintained in the MI/CBT arm at 6 months, this effect was only maintained in the mh GAP IG arm up to 3 months. Additional improvements were seen in HIV treatment outcomes (especially viral load), functionality, and quality of life. Finally, it was feasible to deliver an MI/CBT intervention using a task sharing model. In terms of implementation, this can be done with a modest increase in staffing. Given the negative role AUDs play in the HIV treatment cascade, reduction in alcohol use can help in achieving the UNAIDS’ 90-90-90 goals. Further, effectiveness trials are needed in LMIC with a high prevalence of HIV. When conducting these trials, attention should be paid to patient experiences, such as the ‘double’ stigma of HIV and AUDs.
Alcohol Induced Psychotic Disorder: a comparitive study in patients with alcohol dependance, schizophrenia and normal controls
(Stellenbosch : University of Stellenbosch, 2007-12) Jordaan, Gerhard; Emsley, R. A.; University of Stellenbosch. Faculty of Health Sciences. Dept. of Psychiatry.
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.
Association between motor timing and treatment outcomes in patients with alcohol and/or cocaine addiction in a rehabilitation programme
(Stellenbosch : Stellenbosch University, 2017-12) Young, Susanne Yvette; Seedat, Soraya; Hoof, J. J. M. van; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Psychiatry.
ENGLISH SUMMARY : Introduction: Motor timing deficits have been found in DA system related disorders and, more recently, also in individuals with Substance Use Disorders (SUD). Motor timing is fundamental to our ability to coordinate movements and is defined as a component of temporal brain processing. Modifications to neural systems associated to these domains contribute to motor timing deficits and pathology; however, the underlying mechanisms that lead to these deficits are still poorly understood. A bimodal distribution and evolutionary neurobiological model may provide a useful pathogenic framework for the classification of major psychiatric disorders, including SUD. In this model, major psychiatric disorders (including SUD) may be understood as progressive manifestations of imbalances between dual neural circuitries in the brain. These include an automatic mechanism (referred to as the Drive Mechanism, DM) and a more cognitive-predictive mechanism (referred to as the Guidance Mechanism, GM). To our knowledge, motor timing has not been investigated in populations with SUDs with regard to treatment outcome and relapse. The main question of this study was: Do imbalances between the DM and GM, as expressed in motor timing deficits, differentiate individuals with SUD from normal controls and predict poorer treatment response and relapse? Methods: This study investigated motor timing and its relation to treatment response and relapse in individuals with Alcohol and/or Cocaine Use Disorder (AUD and/or CUD) compared to a Healthy Control (HC) group. Owing to the novelty of the motor task battery, the tested sensitivity values of motor timing parameters were assessed on test retest variability. The possible confounding effects of attention and working memory on motor timing paradigms, and the high impulsivity levels found in individuals with SUD were addressed by comparing the motor task paradigms with a battery of neuropsychological tests. Results: Motor timing was found to be predictive of treatment outcomes at 8 weeks. Synchronisation abilities were predictive, but decision making and motor planning abilities were not predictive. Owing to the small size of the follow up sample, a prediction of motor timing with regards to relapse at 12 months was not possible. Motor timing improved with prolonged abstinence. Specifically, synchronisation abilities improved. Decision making and motor planning abilities did not improve over time. Motor timing performance found in our AUD and/or CUD population only partially supported van Hoof’s proposed model. However, no deficits were found in internal clock rates or the capacity to plan and coordinate actions. Deficits were found in decision making (DM) and synchronisation abilities (GM) in patients versus HC. Decision making abilities were poorer in CUD compared to AUD. No correlation was found between motor timing and impulsivity. Working memory and attention were found to bepredictive of motor timing. Robust test-retest reliability of the test battery was found. Discussion: These findings provide partial support for the deficits in neurocircuitry, as proposed by van Hoof. Additionally, the findings show that motor timing holds prognostic for recovers with prolonged abstinence. These findings may have significant implications for future studies and warrant further investigation in SUD populations going forward.
Brain structural and white matter changes in first-episode schizophrenia and their demographic, clinical and cognitive correlates
(Stellenbosch : Stellenbosch University, 2018-03) Asmal, Laila; Emsley, Robin; Dazzan, Paola; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Psychiatry.
ENGLISH SUMMARY : In schizophrenia, decreased brain volume and altered cortical thinning (especially in the frontal and temporal areas), as well as white matter deficits are described at the first-episode. The relationship between these brain measures and clinical symptoms, whether there is progression, and the extent to which antipsychotic medication contribute to or mitigate those changes remains unclear. The aim of this PhD was to examine cortical thickness, brain volume (cortical, subcortical, white matter) and diffusion tensor imaging data, looking at the relationship between these brain measures and clinical variables in the first year of schizophrenia treatment. This PhD focused on the MRI subcomponent of a larger prospective longitudinal study in first-episode schizophrenia (FES) patients treated with flupenthixol decanoate medication. The thesis integrates the findings of five journal manuscripts that each focused on a clinically relevant neuroimaging question that emerged as we assessed patients in the parent study, namely insight, childhood trauma, neuroimaging predictors of symptom expression, and antipsychotic related brain changes. In our first manuscript, baseline fractional anisotropy (FA) in a number of white matter tracts predicted poorer total insight in 89 FES patients, with a predilection for tracts associated with cortical midline structures. In our second manuscript, the ‘symptom misattribution’ domain of clinical insight was associated with significantly thinner left anterior cingulate and left rostral middle frontal cortices. Our studies address a need for research in larger samples in FES to better understand the neurobiology of insight in schizophrenia. In our third manuscript, baseline FA deficits in cortico-limbic circuitry was associated with childhood trauma in 53 FES patients compared to 51 controls, and there were differential effects of childhood emotional neglect (increased FA) and sexual abuse (decreased FA) on white matter in patients. To our knowledge, at the time of manuscript submission for publication, this was the first study examining the relationship between childhood trauma, FA and FES. For our fourth manuscript, baseline brain measures in 54 FES patients were differentially associated with state and trait symptom expression over 12 months, with global gray matter significantly associated with sensory integration and verbal learning trait scores, cortical volume with verbal learning trait scores, cortical thickness with social and occupational functioning trait scores, and white matter volume with motor coordination state scores. Of potential relevance to patient care is that these neuroimaging deficits at initial presentation in FES may predict enduring trait deficits in cognition, functioning and neurological soft signs. For our final manuscript, total antipsychotic dose was a predictor of substantial cortical brain volume reductions over twelve months of treatment in 23 antipsychotic naïve patients compared to 53 matched controls. Our finding of a significant relationship between antipsychotic dose and cortical volume reduction in this study strongly suggests causality. Future research directions stemming from this PhD include further exploration of our longitudinal data, strengthening our clinical assessments of insight and childhood trauma, connectomic analyses, a multi-modality neuroimaging approach, hippocampal subfield segmentation, and broadening our international collaborations.
Chromosomal aberrations in the Xhosa schizophrenia population
(Stellenbosch : Stellenbosch University, 2008-12) Koen, Liezl; Niehaus, Daniel Jan Hendrik; De Jong, Greetje; Stellenbosch University. Faculty of Health Sciences. Dept. of Psychiatry.
BACKGROUND: Schizophrenia is a heterogeneous illness resulting from complex gene-environment interplay. The majority of molecular genetic work done has involved Caucasian populations, with studies in these and Asian populations showing 2-32% of sufferers to have chromosomal aberrations. So far the discovery of a specific susceptibility mechanism or gene still eludes us, but the use of endophenotypes is advocated as a useful tool in this search. No cytogenetic studies of this nature have been reported in any African schizophrenia population. AIM: The aim of the study was to combine genotypic and phenotypic data, collected in a homogenous population in a structured manner, with the hope of characterising an endophenotype that could be used for more accurate identification of individuals with possible chromosomal abnormalities. METHODOLOGY: A structured clinical interview was conducted on 112 Xhosa schizophrenia patients. (Diagnostic Interview for Genetic Studies, including Schedules for the Assessment of Negative and Positive Symptoms.) Blood samples (karyotyping and/or FISH analysis) as well as urine samples (drug screening) were obtained and nine head and facial measurements were performed. Descriptive statistics were compiled with reference to demographic, clinical and morphological variables. Comparisons between mean differences for these variables were made.
The clinical course and outcomes of first episode psychosis : a study of the acute, medium and long-term outcomes in a cohort rigorously treated in the early phase of illness
(Stellenbosch : Stellenbosch University, 2022-04) Phahladira, Lebogang; Emsley, Robin; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Psychiatry.
ENGLISH SUMMARY: The period surrounding the first episode of psychosis represents a critical period in the natural course of the illness. There are several studies on the nature of the clinical presentation, the effects of treatment, course, and the outcome of the illness. However, there remain several knowledge gaps. This PhD sought to address some of those gaps. The overall aim was to assess the acute, medium- and long-term clinical and functional outcomes of participants with first-episode schizophrenia spectrum disorders who received intensive treatment with a long-acting injectable antipsychotic over a period of 24 months. We reported a well-established finding that psychotic symptoms in patients with first-episode schizophrenia spectrum disorders respond well to antipsychotic treatment. Overall, outcomes were favourable, with 70% achieving symptom remission, 56% functional remission and 61% rating their quality of life as good or excellent (although only 29% met all three of our criteria for recovery simultaneously). Symptom remission may be an important stepping stone to recovery, insofar as very few patients (9%) who did not achieve symptom remission were able to achieve functional remission and a good subjective quality. Our finding on longitudinal assessment of changes in insight was that in contrast to clinicianrated insight, significant impairments in patient-rated insight persisted despite assured treatment. This suggests that insight impairment is more trait- than state-related. We found that depressive symptoms during the early phase of illness are intrinsic to psychosis and responded well to antipsychotic treatment. Regarding negative symptoms, we replicated the two-factor structure, namely an experiential and an expressive domain, although the two subdomains appear closely related rather than being independent entities. Premorbid correlates and treatment response trajectories were similar for the two subdomains. We found that secondary negative symptoms affect the subdomains differentially. Depression affects the experiential subdomain, whereas extrapyramidal symptoms affect the expressive subdomain. A link between lipid metabolism and negative symptoms is suggested in that post-hoc testing indicated that reductions in HDL-cholesterol levels were associated with less improvement in both expressive and experiential subdomain scores. Taken together, our findings support the use of long-acting injectable antipsychotics as a first line treatment in schizophrenia spectrum disorders, perhaps particularly in resource constrained settings such as our own.
Cognitive training in patients with Trichotillomania (Hair-pulling Disorder)
(Stellenbosch : Stellenbosch University, 2019-04) Louw, Derine; Lochner, Christine; Stein, Dan J.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Psychiatry.
ENGLISH SUMMARY : Background: Hair-pulling disorder (HPD), also known as trichotillomania, is a psychiatric condition characterized by recurrent pulling of hair, resulting in hair loss. Patients report repeated but unsuccessful attempts to reduce or stop the behaviour, leading to significant distress, and in some cases, functional impairment. HPD is characterized by impairments in executive functioning including working memory (WM), impulse control (IC) and emotional regulation (ER). Current interventions include Habit Reversal Therapy (HRT) and pharmacotherapy, but a large proportion of patients do not have access to these treatments or do not respond favourably. An easily accessible strategy in the context of scant resources would be particularly welcome. Based on the efficacy of WM training in improving executive functioning, it was hypothesized that this intervention would 1) be efficacious for reducing the symptoms of HPD, 2) improve compromised neurocognitive functions, 3) and be experienced by patients as an acceptable and feasible method of intervention. Methods: A single-blind, randomized, 5-week, 25-session cognitive working memory training (CWMT) program versus a control condition was conducted in 30 participants with a primary diagnosis of HPD. The primary outcome measure was the Massachusetts General Hospital Hair-Pulling Scale (MGH-HPS). The control condition required puzzle building, i.e. the Jigsaw Puzzles program available on the Internet, following the same 5-week protocol as the CWMT, commercially known as the Cogmed Working Memory Training. Assessments at baseline, immediate post-intervention, and at 3-month follow-up, provided information on clinical and neurocognitive data. Both quantitative and qualitative methods were employed. The quantitative data addressed hypotheses relating to treatment intervention outcomes and were analysed using Statistica 13.3. The qualitative data investigated the experience of living with HPD and addressed the acceptability and feasibility of the intervention and were analysed using Atlas.ti 8.1.30. Statistical analysis of the primary outcome and the neurocognitive data were conducted using mixed model repeated measures analysis of variance (ANOVA). The qualitative data were analyzed using a thematic approach. Results: CWMT significantly decreased hair-pulling severity compared to the control condition at 5 weeks and 3 months. Although participants did not demonstrate notable impairments in WM compared with norms, WM improved immediately post-training. Although gains in symptoms and WM were maintained at 3 months, there was no longer a significant difference between the cognitive training and control group. There were no impairments in IC and ER at baseline, and CWMT did not have greater impact on IC and ER than the control condition. Qualitatively, participants indicated that CWMT was feasible and acceptable; furthermore, participation in the study was associated with greater openness about symptoms at home, feeling less isolated, and feeling more supported. Conclusions: This is the first study of CWMT in HPD and demonstrates not only the feasibility and acceptability of this intervention, but also its efficacy. Further work is needed to study the relevant mechanisms, and to assess the effectiveness and cost-efficiency of this intervention in larger pragmatic trials aimed at scaling-up the intervention.
The development and validation of the visual screening tool for anxiety disorders and depression in people living with hypertension and/or diabetes
(Stellenbosch : Stellenbosch University, 2018-12) Ogle, Zimbini; Koen, Liezl; Niehaus, Dana H. J.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Psychiatry.
ENGLISH SUMMARY : People living with hypertension and/or diabetes have an increased prevalence of depression and anxiety disorders. This contributes to functional limitations, poor quality of life, increased financial burden and increased suffering. The identification of these mental disorders can contribute to addressing the burden imposed by them. However, there are barriers to the identification of these disorders, particularly in the South African context. These include a lack of tools that can be applied to the diverse South African cultural and language groups and people with different levels of education; as well as that a number of screening tools fail to meet acceptability for sensitivity in the South African population. Attempts to improve availability of screening tools for use at primary health care have included the translation of screening tools previously developed in high-income countries. However, translated screening tools are often plagued with methodological flaws. In order to address some of these limitations, visual screening tools for depression have been developed. These tools do not require a patient to be able to read and write, and have been found to be appropriate for use in people with low levels of education. They have been shown to be effective in the identification of depression in low-income countries. In this study, I aimed to develop and validate a visual screening tool for both depression and anxiety disorders in people living with hypertension and/or diabetes for use at primary health care level. The items for the visual screening tool were based on the Hospital Anxiety and Depression Scale (HADS). Compared to similar screening tools, the HADS has been found to be an appropriate screening tool for anxiety disorders and depression in people with diabetes, and those with low levels of education. However, the HADS is only appropriate for people who are able to read and write. My study was divided into two phases with each informing the final conclusion. In phase one (reported as one publication), I developed the visual screening tool items by asking an artist, Ms Jane Metelo-Liquito, to draw pictures depicting symptoms of depression and anxiety disorders. The drawings were based on the HADS. These were shown to a group of participants recruited from the general population, primary health care centres and a maternal mental health clinic. This was to ascertain the applicability of the drawings across cultures, languages and varying levels of education. The findings from phase one of the study indicated which drawings were applicable and appropriate for inclusion in the visual screening tool named the Visual Screening Tool for Anxiety Disorders and Depression (VISTAD). In phase two of the study, I validated the VISTAD. Participants diagnosed with hypertension and/or diabetes were recruited from five primary health care centres in the Eastern Cape. This province has been identified to have a high prevalence of hypertension and diabetes. Using the Mini Neuropsychiatric Interview (M.I.N.I) we demonstrated that 40% of our sample had panic disorder, followed by depression (32%), post-traumatic stress disorder (33%), generalised anxiety disorder (17%), and then social phobia and agoraphobia (10% for both). Current available prevalence rates of depression and anxiety disorders in the hypertension and/or diabetes populations are mostly based on research conducted in high-income countries and as such my results are a valuable addition for researchers and clinicians. Using the WHO quality of life assessment instrument (WHOQOL-BREF) as research tool, I found that our participants reported poor quality of life across the domains of physical health, psychological health and environment, but not for the social relationships domain. There were statistically significant differences in the physical and environment domain of people living with hypertension and/or diabetes comorbid with other medical conditions compared to participants without other medical conditions. The majority of participants in my study had lower levels of education, were unemployed and financial dependent on support from others and our results were largely in keeping with available literature in similar groups. The positive association with the social relationships domain could possibly be explained by the fact that most participants were reliant on interdependent social structures. Only 15% of my sample reported hazardous and harmful alcohol use whilst 17% reported any other drug related problems. These are relatively low levels within the South African context but are likely explained by the fact that the majority of my participants were female and that the sample’s average age was 49. The overarching goal of phase two was the validation of the VISTAD (chapter 4) which was developed in phase one. Validation was done against the M.I.N.I and my findings showed that the VISTAD has high accuracy in detecting depression and moderate accuracy in detecting anxiety disorders in adults with a diagnosis of hypertension and/or diabetes attending primary health care centers. The VISTAD is self-administered and any primary health care worker can easily be trained to score it. I demonstrated that it can be administered to patients independent of level of education, language and cultural background. I believe that the VISTAD represents an important contribution towards furthering the integration of the management of mental health conditions into the primary health care system. Firstly, it addresses the challenges posed by cultural, language, educational and time factors when attempting to screen for common mental disorders. Secondly, the VISTAD includes symptoms of depression and anxiety disorders in one screening tool. Literature recommends that the assessment of depressive disorders should include anxiety disorders since these disorders often co-exist in chronic physical conditions. It is well known and widely reported in the literature that primary health care access to mental health specialists is severely limited. Thus, the true integration of mental health care into primary health will improve the early identification and management of depression and anxiety disorders in people living with chronic illnesses. The availability of simple to use and culturally appropriate tools such as the VISTAD brings this goal much closer to becoming a reality.
Efficacy and mechanism of action of intrahippocampalD-cycloserine in an animal model of Posttraumatic Stress Disorder (PTSD)
(Stellenbosch : Stellenbosch University, 2015-03) Fairbairn, Lorren Rosli; Seedat, Soraya; Daniels, W. M. U.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Psychiatry.
ENGLISH SUMMARY : Posttraumatic stress disorder (PTSD) has been described as a persistent (Bremner et al., 1996) and incapacitating (Zatzick et al., 1997; Mendlowicz &Stein 2000) psychiatric disorder which occurs after exposure to a potentially traumatic event (DSM-5, APA 2013). Exposure based therapy (EBT) is one of the most common and effective therapies for posttraumatic stress disorder (Mendes et al., 2008). The procedure involves controlled exposure to the feared stimulus in the absence of any overt danger. EBT in humans is procedurally very similar to fear extinction training in animal models of emotional learning, such as fear conditioning (Norton & Price, 2007). It has previously been shown that dysfunctional fear extinction underpins PTSD pathophysiology (Keane et al., 1985; Cohen et al., 2006; Amstadter et al., 2009). With recent studies demonstrating fear extinction as an essential process for studying putative pharmacotherapies for clinical use in PTSD treatment. One such novel pharmacological agent, D-cycloserine (DCS), has been investigated in both preclinical and clinical studies of anxiety and has been reported to facilitate extinction of learned fear in rats and to promote exposure-based therapies in humans (Walker et al., 2002; Ledgerwood et al., 2003; Davis et al., 2006; Bontempo et al., 2012). DCS is a partial agonist of the N-methyl-D-aspartate receptor (NMDAR) and exerts its effects by binding to the glycine regulatory site of the NMDA complex. In addition, these glutamatergic receptors, specifically the hippocampal NMDARs and their subsequent signalling pathways have been implicated in fear extinction. PTSD affects individuals in all sectors of society and is as much a concern with respect to children as to adults. Considering that adolescence is a period of heightened vulnerability for mood and anxiety disorders, it is crucial to observe the effects of trauma on this developmental stage. Therefore the main aim of this study was to determine whether intrahippocampal infusions of DCS could reverse the PTSD phenotype, as displayed by our animal model, in both adolescents and adults with special focus on fear extinction. In the current study, we used a fear conditioning paradigm consisting of a brief, intense electric footshock (1.5 mA) and a neutral tone (80 dB, 9 kHz) to represent the traumatic event and investigated the efficacy and molecular mechanism of action of DCS on the behaviour and neurochemistry of adolescent and adult rats. The present study was particularly interested in the effects of DCS on hippocampal brain-derived neurotrophic factor (BDNF), hippocampal NMDAR expression levels, factors downstream of the NMDA signalling pathway (i.e. neuronal nitric oxide synthase) and protein changes in the hippocampus (HC) of fear conditioned and DCS-treated animals. Our animal model generated the following key findings. Firstly, various behavioural tests demonstrated that fear conditioned rats exhibited a PTSD-like disorder as shown by their increased and sustained conditioned fear response and increased anxiety-like symptoms. These effects were reversed by intrahippocampal DCS infusions, as assessed by behavioural freezing. Secondly, an upregulation of hippocampal NMDARs was noted in fear conditioned rats, while repeated administration of intrahippocampal DCS reduced this effect. Thirdly, intrahippocampal DCS infusions enhanced dorsal hippocampal BDNF expression in DCS treated groups, with fear conditioned rats expressing the lowest BDNF levels. Fourthly, intrahippocampal DCS administration elicited similar patterns in adolescents and adults with regards to fear extinction i.e. a decreased fear response was noted in both age groups after DCS administration. Lastly, we observed that hippocampal protein expression differed between adolescent and adult rats. Most proteins were distinctly expressed in either of the two age groups. The protein, neurabin-2 was specifically expressed during the adolescent period. Furthermore, footshock led to an increase in adolescent protein expression, whereas DCS treatment led to a decrease in adolescent protein expression. Overall, this study supported and extended previous findings that DCS has a therapeutic effect on fear conditioning by enhancing extinction of anxiety-like symptoms in rodents. We were able to show that animals subjected to fear conditioning/trauma show signs of alterations in proteins involved in neuronal plasticity, calcium (Ca2+) homeostasis, cellular stress, cell cycle arrest, initiation of apoptotic mechanisms and cell signalling dysregulation. These proteins all have a role in one or more of the neurochemical parameters as examined in our PTSD model i.e. interact with the HC, BDNF, nNOS or NMDARs. Therefore, additional studies are needed to elucidate the relationship between epigenetic modifications and the resulting proteomic responses as demonstrated in our study. In addition, the role of BDNF in PTSD has to be further investigated, be it as a biomarker or as adjunctive therapy for PTSD.
Epidemiological, phenomenological, and treatment aspects of trauma and posttraumatic stress disorder in children and adolescents
(Stellenbosch : University of Stellenbosch, 2005-12) Seedat, Soraya; Emsley, R. A.; Stein, D. J.; University of Stellenbosch. Faculty of Health Sciences. Dept. of Psychiatry.
Many gaps remain in our current state of knowledge about the epidemiology, phenomenology, neurobiology, and psychopharmacology of posttraumatic stress disorder (PTSD) in children and adolescents. Empirical evidence, particularly in non-Western settings, is sparse and there is little convergent understanding of the interrelationship of epidemiological factors, PTSD symptom expression, full and partial syndromes, disorders comorbid with PTSD, and pharmacotherapeutic interventions. Clinicians are faced with the difficult task of treating this often complicated and debilitating disorder in youth in the absence of data from well-controlled clinical trials. The studies detailed here are a point of departure for understanding the confluence that exists between epidemiological, phenomenological, and pharmacotherapeutic aspects of adolescent PTSD. Two studies were conducted to investigate the prevalence and effects of violence exposure and PTSD, clinical and functional correlates of full and partial syndromes, and associated gender differences in school and clinic samples, respectively. Two preliminary open-label trials assessed the efficacy and safety of a selective serotonin reuptake inhibitor (SSRI) in adolescents with at least moderate severity PTSD. The results indicate that (i) partial PTSD is a common nosological entity in adolescents, (ii) gender-related differences in PTSD, even if not manifest in differences in prevalence (i.e., in the rates of trauma exposure and full and partial PTSD), may well manifest in symptom expression (i.e., higher symptom burden in girls), associated morbidity, and functional impairment, and (iii) SSRIs may be effective in treating core PTSD symptoms in this age group. While not yet demonstrated, the partial subtype may have similar biological underpinnings to full PTSD in adolescents and may benefit from similar pharmacotherapeutic interventions. This is an area deserving of further investigation. Controlled SSRI data are needed to establish if these should be agents of choice for paediatric PTSD.
Epigenomic analysis of posttraumatic stress disorder in female rape survivors in South Africa
(Stellenbosch : Stellenbosch University, 2021-03) Nothling, Jani; Hemmings, Sian M. J.; Seedat, Soraya, 1966-; Abrahaams, Naeema; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Psychiatry.
ENGLISH SUMMARY : Compared to other trauma types, rape is associated with a high risk of developing posttraumatic stress disorder (PTSD). Women are at increased risk of developing PTSD compared to men and are also more frequently victims of sexual assault. PTSD is a complex, multifactorial disorder and an array of demographic, trauma-related, psychological and genetic putative risk and protective factors mediate or contribute to the development and course of the disorder. Few studies have comprehensively investigated demographic and psychological risk and protective factors for PTSD in a longitudinal prospective design, especially beyond the 3-month post-rape period and in low- to medium-income countries. There are currently no known epigenome-wide association studies (EWASs) investigating differential methylation in relation to PTSD in (1) an African population and (2) a sample of rape-exposed women exclusively. There are also no known studies investigating longitudinal change in the hypothalamic-pituitary-adrenal (HPA) axis associated candidate gene FK506 binding protein (FKBP5) in relation to PTSD in a sample of rape-exposed women exclusively. In this study we investigated the demographic, rape/assault-related, psychological, genetic (FKBP5) and epigenetic (epigenome-wide differential methylation) risk and protective factors associated with the development and course of PTSD symptoms over six months. Self-report measures and specimen collection was completed at baseline (within 20 day after the rape), 3-months and 6-months post-rape as part of the Rape Impact Cohort Evaluation (RICE) study. The RICE sample consisted of 852 Black African rape-exposed women, between the ages of 16 and 40 years and from a low socio-economic background. We found that baseline demographic, rape/assault-related and psychological protective factors were not significant predictors of PTSD symptoms over time. Baseline depression and rape stigma were significant psychological risk factors for the development and course of PTSD post-rape. We also identified one intergenic CpG site (cg01700569) that was differentially methylated in relation to PTSD status at 3-months post-rape on a genome-wide level. Thirty-four differentially methylated regions were identified and included a region in the HPA-axis-associated adenylate cyclase activating polypeptide 1 (ADCYAP1) gene and the neuroendocrine-associated brain-specific serine/threonine-protein kinase 2 (BRSK2) gene. Decreased BRSK2 and ADCYAP1 methylation at 3-months and 6-months post-rape was associated with increased PTSD symptom scores at the same time-points. Decreased FKBP5 methylation was a predictor of increased PTSD symptom scores at 3-months and 6-months post-rape. High childhood trauma and the CC genotype of FKBP5 rs1360780 resulted in decreased FKBP5 methylation and increased PTSD scores at baseline. The study builds on existing literature, highlighting the psychological risk factors for the development and course of PTSD in rape-exposed women. Methylation findings also build on the existing literature regarding the role of epigenetics in PTSD, although the genome-wide finding implicating differential methylation of BRSK2 in the development of PTSD is a novel finding in human studies. The study provides evidence that both psychological and biological factors have an impact on the symptom trajectory of PTSD and that both should be considered when designing and implementing interventions for the treatment of PTSD post-rape.
Establishing modified mental health assertive treatment programs in a developing country
(Stellenbosch : Stellenbosch University, 2016-12) Botha, Ursula Alexandra; Niehaus, Dana J. H.; Koen, Liezl; Stellenbosch University. Faculty of Medicine and Health Sciences. Department of Psychiatry.
ENGLISH SUMMARY : An increasing demand for acute inpatient beds has put pressure on psychiatric services in the Western Cape Province of South Africa. While this is not unusual compared to elsewhere in the world, this project aims to find an assertive intervention that not only successfully reduces inpatient usage, but is also sustainable in a low-resource setting. It also attempts to address the repercussions of the deinstitutionalization process, which include a rise in homelessness, an increase in “revolving door” (RD) patients, inadequate discharge planning and a reliance on poor community resources. RD patients also contribute markedly to the need for inpatient beds and costs associated with acute inpatient care, placing an additional burden on health care. Interventions that reduce readmissions in high frequency users (HFUs) help decrease costs associated with inpatient care and improve bed availability. Assertive Community Treatment (ACT) refers to initiatives that incorporate capped caseloads, frequent contacts, home visits and pro-active follow-up. Results from international studies show that ACT interventions may be effective in reducing readmission rates in HFUs in settings where standard care is less comprehensive. The project was divided into four studies, each contributing to inform the final conclusion. Study 1: This was a randomized control trial, which compared a group of low frequency users (LFUs) of mental health services with a group of HFUs. The purpose was to ascertain if local HFUs shared the same characteristics as described in international literature, as we intended to modify a model that had been proven to be effective in an international sample of HFUs. Our results indicated that local HFUs had similar characteristics to those described in the literature; they were more likely to be young males, were more severely ill and more likely to use illicit substances. Study 2: In this study we assessed the effect of a modified intervention on inpatient usage, illness severity and social functioning by comparing intervention participants to a control group over a 12-month period. The intervention was a modified ACT service, with intervention patients receiving fortnightly contacts, pro-active follow-up and 50% of all visits at home. At 12-month follow-up, patients in the intervention group were significantly less ill, reported higher levels of functioning and had significantly less readmissions and overall days spent in hospital (DIH). Study 3: In this study we report on the effect the previously described, modified assertive intervention had on inpatient usage after 36 months. It is important to be able to demonstrate sustained outcomes, since outcomes may tail off after the first 12 months. We compared readmissions and DIH of the same intervention group, with the same control group from our previous study. In this study, we were able to demonstrate that the positive outcomes we reported on in our 12-month follow-up study can be sustained over a 36 month period. The intervention group still had significantly less readmissions and DIH compared to the control group. Despite the success of ACT interventions locally, these highly specialized and focused interventions are expensive and possibly not justifiable in a low-income setting. Study 4: This study was conceptualized in an attempt to find a midway between a highly focused intervention “for few” and the less supportive standard care service which the majority of patients have access to. The intervention was a phone-based intervention, which aimed to support patients and families with frequent phone contacts and would facilitate the patients’ use of the existing standard care service. At 12 month follow-up, there was no difference in inpatient usage between the intervention and the control group. Use of illicit substances was high in both groups. Conclusion: Assertive interventions are effective in reducing inpatient care in our local setting, even when modified to allow for larger caseloads and less frequent visits. However, once home-visits and frequency of contacts are excluded from the model, programme efficacy is reduced significantly. These findings are important in the development of future community-based mental health services, as they will be able to suggest the best possible structure of prospective programmes for better patient results and more efficient and cost-effective programme management.
Examining the potential role of adiponectin in the development of posttraumatic stress disorder in female rape survivors in South Africa
(Stellenbosch : Stellenbosch University, 2022-12) Vuong, Eileen; Seedat, Soraya, 1966-; Abrahams, Naeemah; Hemmings, Sian Megan; Peer, Nasheeta; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Psychiatry.
ENGLISH SUMMARY: Background: Sexual violence, including rape, is associated with adverse mental and physical health outcomes, including post-traumatic stress disorder (PTSD) and cardiometabolic diseases (CMDs). CMDs are prevalent in individuals with PTSD and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis have been implicated in both these disorders. A blood-based biomarker of future susceptibility to PTSD and CMDs following rape, could allow for the early identification of at-risk individuals when disease trajectories may still be reversible. Adiponectin is an anti-inflammatory, insulin-sensitizing, adipose-secreted cytokine that has reciprocal relationships with the HPA axis and cortisol secretion. Higher adiponectin levels have been associated with a lower risk of metabolic syndrome (MetS), a clustering of multiple cardiometabolic risk factors whose pathologic origins arise from insulin resistance and adiposopathy. Although cross-sectional associations between adiponectin and PTSD have been described, no prospective studies of adiponectin in PTSD exist. Aims: In this dissertation, adiponectin is investigated as a candidate biomarker for new-onset PTSD and MetS following rape. Study objectives were completed utilising (1) serum adiponectin levels (s-ADP), (2) adiponectin gene (ADIPOQ) polymorphisms and (3) hair cortisol concentrations (HCC), a HPA axis measure that reflects long-term cortisol production. Methods: This study is nested within the Rape Impact Cohort Evaluation (RICE) study, which enrolled 1 799 black African female participants (N = 852 rape-exposed [RE] and N = 947 rape-unexposed [RUE]) between the ages of 16 and 40 years from KwaZulu-Natal Province. Data collected at baseline and at 3-, 6- and 12-month follow-up visits were utilised in this study to determine prevalent and incident outcomes. This included history (sociodemographic, medical history, mental health), physical examination (anthropometry, blood pressure), and biochemical investigations. Results: A systematic review and meta-analyses of the existing literature demonstrated an inverse association between circulating adiponectin levels and PTSD. In the RICE cohort, higher s- ADP was associated with a reduced risk of PTSD at three and six-month follow-up. However, the interaction of rape x s-ADP on PTSD was not significant. No ADIPOQ variant was shown to be associated with PTSD symptom severity. Serum adiponectin was shown to be significantly associated with MetS prevalence at baseline. However, no associations with new onset MetS incidence were shown at the 12-month follow-up. In the RE, the rs2241766TT genotype was shown to influence s-ADP levels and significantly reduce the risk of MetS incidence at 12 months. Lastly, no evidence of an interactive effect for s-ADP and HCC in predicting PTSD over time was found. Conclusion: This study supports the hypothesis that adiponectin is a potential candidate risk biomarker for PTSD and MetS. Whether adiponectin is a candidate biomarker of risk for PTSD following rape has yet to be established. The lack of prospective association between s-ADP and MetS may be explained by the relatively young study cohort and short period of follow-up and requires further long-term investigation. Future research directions stemming from this PhD include examination for associations of s-ADP and ADIPOQ variants with traumas other than rape, cumulative trauma exposure over time and Mendelian Randomization studies.
Exploration of parental reflective function and mother-child interaction in a South African sample of women with peri- and postpartum psychosis
(Stellenbosch : Stellenbosch University, 2020-12) Voges, Juane; Niehaus, Dana J. H.; Berg, Astrid
ENGLISH SUMMARY : Background: Severe mental illness in the peripartum period may exert a significant and detrimental impact on maternal caregiving and infant attachment. The experience of psychotic symptoms during pregnancy or the postpartum period may further contribute to the development of attachment difficulties and poor outcomes. Attachment theory was used as a guiding framework to examine the experience and impact of peripartum psychosis on the mother-infant dyad. Infants of mothers with psychosis are at risk of developing insecure or disorganised attachment. Mothers with psychotic disorders are likely to display poor sensitivity and responsiveness in interaction with their infants. Parental reflective functioning (PRF) is the capacity to hold in mind one’s own and one’s child’s mental states. Impairments in PRF may be a potential mechanism for impairments in attachment and quality of mother-infant interaction. Peripartum psychosis may place the mother-infant dyad at risk due to the nature of symptoms, the frequent need for psychiatric admission and separation between mother and infant. Studies of maternal psychopathology and infant outcomes in South Africa have focussed on maternal depression or trauma. To our knowledge, there are no studies examining the impact of maternal psychosis on parenting in South Africa. There have been limited studies examining PRF in South Africa; however, none have focussed specifically on how this capacity influences caregiving behaviours among mothers who have experienced psychosis in the peripartum. This study set out to explore PRF and quality of mother-infant interaction in a sample of mothers with peripartum psychosis. We hypothesised that experiences of peripartum psychosis will be associated with 1) lower PRF and 2) poorer quality of mother-infant interaction. Further, we hypothesised that 3)impairments in PRF will be correlated with a poorer quality of mother-infant interaction. Methods: The study followed an exploratory, quantitative and descriptive design. Forty mothers with predominantly bipolar disorder or schizophrenia were recruited following experiences of psychosis during pregnancy or early postpartum in order to determine their level of PRF and quality of interaction with their infants. A detailed interview was conducted to obtain information pertaining to demographic and clinical characteristics, as well as pregnancy and postpartum experiences. PRF was coded from the Parent Development Interview and the quality of interaction was assessed following an unstructured play interaction between mother and infant. Two-sample t-tests were conducted to examine whether PRF or mother-infant interaction was influenced by demographic, clinical, pregnancy, or postpartum variables. Pearson’s correlation coefficients were calculated for correlations between PRF and interaction variables. Results: Psychosocial risk factors were prevalent among this group of mothers who experienced peripartum psychosis. High rates of unplanned pregnancy and maternal substance use during pregnancy was also observed and the majority mothers had a psychiatric admission, which necessitated early separation from their infants. The majority of mothers (65.00%) demonstrated a pre-mentalising level of PRF (Mean = 4.10). However, this capacity was not impaired in all mothers with peripartum psychosis. A large proportion of mothers (75.00%) exhibited the potential for adequate to complex PRF. Dyads achieved moderate scores for overall quality of interaction, maternal sensitivity, and infant social engagement and had a low level of dyadic reciprocity. These findings appear to support our hypotheses that mothers’ experience of peripartum psychosis was associated with poorer PRF and quality of mother-infant interaction. Socio-demographic risk factors and factors related to pregnancy and postpartum experiences influenced PRF and quality of mother-infant interaction. A low positive correlation between PRF and quality of interaction was found (r = .40), which was weaker than we hypothesised. Conclusions: Peripartum psychosis was associated with lower PRF and poorer mother-infant interaction for the majority of our sample. Mothers who experienced peripartum psychosis may benefit from interventions targeting both PRF and quality of mother-infant interaction. Additionally, the provision of joint admissions, and pro-active psychoeducation about pregnancy planning and substance use are recommended.
Hair cortisol as a neuroendocrine biomarker to evaluate the impact of chronic stress on the interaction between neuropsychiatric disorders and metabolic syndrome
(Stellenbosch : Stellenbosch University, 2020-03) Van den Heuvel, Leigh Luella; Seedat, Soraya, 1966-; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Psychiatry.
ENGLISH SUMMARY : Individuals with neuropsychiatric disorders (NPDs) demonstrate increased rates of cardiovascular disease (CVD) and metabolic syndrome (MetS). There is evidence of dysregulated hypothalamic pituitary adrenal (HPA) axis functioning in both NPDs and CVD and the HPA-axis may be a shared mechanistic pathway contributing to NPD-CVD comorbidity. Very few studies have, however, directly examined the association between NPDs, CVD risk and HPA-axis function. Hair cortisol concentrations (HCC), reflecting longerterm systemic cortisol levels, can provide insight into the role of HPA-axis dysregulation in the occurrence of CVD risk, as defined by MetS, in NPDs. This study was a neuroendocrine ancillary study to ‘Understanding the SHARED ROOTS (SR) of Neuropsychiatric Disorders and Modifiable Risk Factors for Cardiovascular Disease’. SR was a cross-sectional matched case-control study investigating the pathways contributing to the comorbidity of MetS in NPDs and included three NPD cohorts (posttraumatic stress disorder (PTSD), schizophrenia and Parkinson’s disease). This study investigated the role of HPA-axis dysfunction, as measured by HCC, in the three NPDs as compared to controls and in relation to NPD-MetS co-occurrence. We demonstrated that HPA-axis function was altered in the three NPDs, with higher HCC in PTSD patients than trauma exposed controls, lower HCC in patients with schizophrenia than controls and higher hair cortisone levels, but not HCC, in Parkinson’s disease patients than controls. MetS was not associated with HCC in any of the individual cohorts. The lack of significant findings related to MetS may have been due to limited statistical power to detect significant associations in the individual cohorts. Additionally, as this is one of the first studies investigating HCC in South Africa and the majority of studies have been conducted in developed regions, we sought to identify basic determinants of HCC in a South African mixed ancestry control sample. The main determinants associated with HCC were age, level of education, duration of sun exposure, hair product use, duration of sample storage and breastfeeding in women. We also demonstrated that resilience, but not self-perceived stress, was significantly inversely associated with HCC, underscoring the importance of identifying stress-resilience indicators of HCC in non-pathological samples. Finally we also found that poorer working memory performance was associated with higher HCC, suggesting an association between a neuroendocrine marker of chronic stress and working memory deficits. This is the first study to utilise a measure of longer-term HPA axis function to investigate the links between HPA-axis, NPDs and CVD risk. Considering the high burden of CVD in NPDs, this study provides a step towards better understanding the role played by chronic stress, as reflected by long-term HPA axis dysfunction, in the co-occurrence of CVD in NPDs. Furthermore, this study provides insights into the role of HPA-axis dysfunction in relation to clinical conditions and subjects of relevance to South Africa and contributes to broader geographic, cultural and ethnic representation in hair cortisol research.
Hormones in hair as possible predictive biomarkers of posttraumatic stress symptoms in women who have been raped
(Stellenbosch : Stellenbosch University, 2020-12) Marx, Melanie; Seedat, Soraya, 1966-; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Psychiatry.
ENGLISH SUMMARY: There is a gap in the literature with regard to researching long-term secretion of cortisol, as well as other hormones (cortisone, testosterone, progesterone, and dehydroepiandrosterone [DHEA]) in hair samples of women with posttraumatic stress symptomatology (PTSS) and who have been victims of rape. Cortisol and other steroid hormones measured in hair over a longer time window may be predictive biomarkers of PTSS. This longitudinal study, based in Kwa-Zulu Natal (KZN), compared hormone concentrations between groups (rape-exposed [RE] and controls) over time. The first time point was at the baseline visit (samples and data collected within 20 days post rape), which provided an approximate three-month window of hormone concentrations, preceding the rape trauma. The second sampling was at three months post rape and this covered the window between the baseline assessment and three months post rape. The last time point was at six months post rape, providing concentrations in the window between three- and six months post rape. Furthermore, the present study sought to examine differences in PTSS between and within groups at different time-points (baseline, three months, and six months post rape). The third aim of the present study was to conduct an analysis of temporal correlations between PTSS and hormones, as measured at baseline, three months, and six months post rape. Lastly, the study sought to establish whether pre-trauma hormone concentrations were predictive of the development of PTSS at baseline, three months and six months post rape. There were no significant differences between groups at different time-points (baseline, three months, and six months) with regard to hair hormone concentrations. There were significant differences in PTSS between groups, and several, but weak, significant correlations were found between hormone concentrations and PTSS, as well as PTSD symptom clusters (reexperiencing/ intrusion symptoms, avoidance/numbing symptoms, hyperarousal, as measured by the Davidson Trauma Scale [DTS]). Pre-trauma cortisol concentrations were significantly correlated with baseline (within 20 days post rape) total PTSD symptoms, reexperiencing/ intrusion symptoms, avoidance/numbing symptoms, hyperarousal. Cortisone concentrations, as measured at six months (i.e. from three to six months post rape) significantly correlated with avoidance/numbing symptoms at three months post rape. A significant, but weak, negative correlation was found between dehydroepiandrosterone (DHEA) concentrations as measured at three months (i.e. from baseline to three months post rape) and reexperiencing/ intrusions at three months post rape. A significant, but weak, positive correlation was found between DHEA as measured at six months (i.e. from three to six months post rape) and total PTSS, as well as re experiencing/intrusion symptoms at three months post rape. Hormone concentrations were not predictive of the development of PTSS. Within 20 days post rape, three significant predictors of PTSS were identified. The strongest predictor of PTSS was depression, followed by previous trauma (trauma load / cumulative trauma), and perceived stress. At three-month follow-up, the strongest predictor of PTSS was trauma load, followed by depression. At six-month follow-up, no significant predictors of PTSS were identified. This is the first study to examine hair cortisol and other hair hormone concentrations in female rape victims with PTSS compared to controls.
The identification of novel susceptibility genes involved in anxiety disorders
(Stellenbosch : Stellenbosch University, 2014-12) McGregor, Nathaniel Wade; Lochner, Christine; Hemmings, Sian; Kinnear, Craig; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Psychiatry.
ENGLISH ABSTRACT: The etiology of anxiety disorders remains incompletely understood. Clear evidence for a genetic component has been proposed; however, there is also an increasing focus on environmental factors and the interaction between these and the genetic components that may mediate (anxiety) disorder pathogenesis. No single gene or genetic component has been explicitly identified as being involved in the development of anxiety disorders. This is most likely due to a number of reasons, which include, for example, the heterogeneity of anxiety disorders, the contribution of environmental factors and methodological limitations (e.g. small sample size) of research studies. Until now, genetic association studies usually focused on one particular psychiatric disorder at a time. However, with the difficulty in identifying susceptibility genes and/or loci in heterogeneous disorders like obsessive-compulsive disorder and other conditions in the anxiety spectrum, it is perhaps timely to consider multivariate genetics and epidemiological studies in a number of disorders sharing a core characteristic – such as anxiety. In addition to genetic underpinnings, a number of environmental variables have also been identified as risk factors for pathological anxiety, including adverse life events like childhood physical and sexual abuse. The hypothesis for this project is that a pre-existing genetic vulnerability (or genetic risk) interacts with the impact of adverse life events to result in the development of one or more anxiety disorder(s). Considering phenotypic overlap amongst the anxiety disorders, it is likely that diverse networks of genes and/ or interacting pathways are responsible for the phenotypic manifestations observed. Sprague Dawley rats exhibiting behaviours indicative of anxiety in the context of environmental stressors (maternal separation and restraint stress) were used as model for the identification of novel susceptibility genes for anxiety disorders in humans. The striatum has previously been implicated as a candidate in the brain architecture of anxiety pathogenicity, and is also a site exhibiting a high degree of synaptic plasticity. The synaptic plasticity pathway was investigated using the dorsal striatum of the rat brain and several genes were identified to be aberrantly expressed in “anxious” rats relative to controls (Mmp9, Bdnf, Ntf4, Egr2, Egr4, Grm2 and Arc). In humans, it was found that the severity of early adversity was significantly and positively associated with the presence of an anxiety disorder in adulthood. When the human homologues of the susceptibility candidate genes that were identified using the animal model were screened in a human cohort of patients with obsessive-compulsive disorder (OCD), panic disorder (PD) or social anxiety disorder (SAD) (relative to controls), five single nucleotide polymorphisms (SNPs) were found to be significantly associated with these conditions. Four of these SNPs were also found to significantly interact with the severity of childhood trauma. Haplotype analysis of variants within the identified susceptibility candidates revealed novel haplotype associations, four of which are located in the MMP9 gene. Notably, this the first study to link these particular mutations in the MMP9 gene with anxiety disorders and this finding is consistent with previous work suggesting that MMP9 is involved in conditions like cardiovascular disease and cancer which have been associated with increased prevalence of anxiety disorders. In conclusion, this project yielded important findings pertaining to the etiology of anxiety disorders. The use of a combined anxiety disorders cohort (OCD, PD and SAD) may suggest that the associations found here may hold true for anxiety disorders in general and not only for a particular clinically delineated condition. Childhood trauma was confirmed as an increased susceptibility risk for anxiety disorders. Also, this research contributed several novel susceptibility genes (MMP9, EGR2, EGR4, NTF4, and ARC), five significant SNP associations, four significant SNP-environment interactions and five haplotype associations (within MMP9 and BDNF) as candidates for anxiety pathogenicity. The identified polymorphisms and haplotypes were demonstrated to be associated with susceptibility to anxiety disorders in a gene-environment correlation and gene-environment interaction.
The impact of cannabis and methamphetamine use on clinical and functional aspects of outcome in first-episode Schizophrenia patients : a longitudinal study
(Stellenbosch : Stellenbosch University, 2021-12) Scheffler, Frederika; Emsley, Robin (Psychiatrist); Du Plessis, Stefan; Kilian, Sanja; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Psychiatry.
ENGLISH SUMMARY : Schizophrenia spectrum disorders, which schizophrenia, schizophreniform, and schizoaffective are severe and disabling disorders by a range of symptoms that psychosis, apathy and withdrawal, mood and impairment. "ness, hereafter referred to as schizophrenia spectrum or SSD, often starts to manifest during adolescence or early adulthood, and may have a lifelong This negative impact already conferred by schizophrenia spectrum disorders is further by a high rate of comorbid substance use. Despite high rate of comorbid substance abuse in schizophrenia spectrum disorders in South Africa, this population has remained under-researched in our setting. Specifically, cannabis and methamphetamine are two most commonly elicit substances in the Western Cape. Although there is literature on the role of cannabis and in the context of SSD, a number of questions as yet remain unanswered. Addressing such questions is necessary, especially in the South African context as resources for mental health are limited. The primary objective of this study was to investigate the impact of cannabis and methamphetamine use on baseline symptom severity and brain structure, and on clinical outcomes over 24 months of treatment with a long-lasting injectable antipsychotic in patients with a Schizophrenia spectrum disorder. Based on the nature of our cohort, as well as recent developments in the literature, we focussed specifically on the effects of cannabis and methamphetamines, as the two most used illicit substances in our region, and because of the availability of good data on these substances. We hypothesised that firstly, use is associated with poor psychopathology outcomes and higher relapse rates in first-episode schizophrenia spectrum disorder patients for whom treatment adherence is assured (objective I); cannabis methamphetamine have independent, and dose- time-dependant effects on cognitive functioning in first-episode schizophrenia spectrum disorder patients (objective II); cannabis use is with pre-treatment hippocampal volume reductions in first-episode schizophrenia patients compared to matched controls (objective III); First-episode schizophrenia spectrum disorder patients who use cannabis are at risk for treatment-emergent metabolic syndrome changes (objective IV). Regarding the selection of brain structural regions, we choose the hippocampal subfields, based on the recent development of software to accurately measure the subfields, together with an emerging literature on the relevance of the hippocampus in substance abuse. Specifically, this project investigated differences between First-Episode Schizophrenia Spectrum Disorder patients with and without cannabis and/or methamphetamine use in terms of relapse rates, psychopathology, functionality and quality of life, cognitive function, body mass and metabolic changes, and pre-treatment volumes. This sample consisted of 126 patients with a schizophrenia spectrum disorder and 100 healthy controls were similar in age, sex, and educational attainment. Each sub-study reported on in the present dissertation included a subset of the larger sample based upon the inclusion and exclusion criteria for each sub-study. First, regarding treatment response, we found little evidence for an effect of cannabis use on clinical improvement over 24 months in schizophrenia spectrum disorder patients. That being said, relapse events were more common in cannabis users compared to their non-using counterparts. Our findings point to an important role for non-adherence in previously reported poorer treatment outcomes in cannabis users, and a direct effect for cannabis in reducing the relapse threshold. Second, we found that methamphetamine use, but not cannabis use, was associated with poorer cognitive performance over the treatment period. Third, we found differential illness-specific associations with cannabis use and hippocampal subfield volumes, specifically subiculum volumes in cannabis using first-episode SSD patients. And lastly, compared to non-users, first-episode SSO patients who used cannabis gained less weight and showed less deterioration of lipid pones during the treatment period. Both cannabis and methamphetamine influence outcome over first two years of treatment in first-episode spectrum disorders. Some of our findings were contrary to our expectations have become foundation for future projects. In conclusion, our study highlights the benefits of the use of long-acting injectable antipsychotics for first-episode schizophrenia disorders, perhaps particularly in individuals who are currently using substances.
Implementation of international treatment guidelines in the treatment of schizophrenia : a study of the effects of an evidence-based seminar on the knowledge and treatment habits of a sample of international psychiatrists
(Stellenbosch : University of Stellenbosch, 2007-12) Joubert, Andre Francois; Emsley, R. A.; University of Stellenbosch. Faculty of Health Sciences. Dept. of Psychiatry.
This study reports on the effect of seminar education by studying changes in knowledge, attitude and behaviour to haloperidol prescribing patterns of psychiatrists who In summary, this study demonstrated a direct relationship between seminar attendance and changes to selected minimum effective haloperidol dose and duration of treatment. However, seminar attendance did not appear to be a significant factor in changes to antipsychotic class used for treatment and changes in optimal effective haloperidol dose: rather a change in the level of “background” knowledge of participants was most likely responsible. This study also found individual participant characteristic differences in those who did change treatment duration and minimum effective dose. In conclusion, this study showed that the successful integration of international treatment recommendations into daily psychiatric practise could be facilitated by the use of appropriate educational seminars. Not all attendees benefit i.e. “learn”, but those needing to “learn” most do - i.e. those who need to change their prescribing habits most to meet internationally accepted guidelines. The peer exposure provided allows a format for informed discussion and the practise of evidence-based medicine. The judicious use of such seminars should result in better treatment options and outcomes for patients.attended evidence-based schizophrenia seminars presented by the Lundbeck Institute in Denmark. The objectives of the study were two-fold. Firstly, it set out to determine whether changes actually occurred in the post-seminar haloperidol prescribing behaviour of participants. This was done by analysing changes in choice of optimal haloperidol dose (both in acute treatment i.e. most effective dose and maintenance treatment i.e. minimum effective dose), selected duration of treatment (for first- and multi-episode schizophrenia patients) and drug-class used (conventional versus new generation antipsychotic). The study then investigated whether these changes (if they occurred) could be ascribed wholly or in part to the effect of schizophrenia seminar attendance, or whether other factors e.g. scientific progress over time in understanding schizophrenia and its treatment (“background” knowledge) and differences between participant datasets studied (only paired pre- and post-seminar data were used in this study) also played a role. Secondly, it attempted to identify factors predictive of seminar participants changing their haloperidol prescribing behaviour post-seminar i.e. what were the factors that predisposed some attendees to change their prescribing behaviour? This was done by analysing the effect that pre-seminar prescribing behaviour, participant nationality, patient caseload, work experience and workplace environment had on post-seminar behaviour. Results show that changes did occur in post-seminar haloperidol prescribing behaviour, but that they were not always due to an effect of seminar attendance. Only the changes in the minimum effective haloperidol dose and duration of treatment for first- and multi-episode schizophrenia patients could validly be ascribed to the effects of schizophrenia seminar attendance. Furthermore, multivariate analysis of the factors relating to these changes found that a participant was most likely to change their selected minimum effective haloperidol dose to be more in line with internationally accepted standards if they i) selected above the target dose pre-seminar, ii) had a relatively low caseload comprised mainly of schizophrenia patients and iii) came from either Greece, Germany, Britain, Spain, Italy or some other Eastern European country. The single most important factor related to changes in duration of treatment was found to be pre-seminar behaviour: respondents below the recommended duration of treatment increased their duration of treatment significantly.

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