Doctoral Degrees (Psychiatry)
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- ItemA randomised controlled trial of a clinician-monitored 'PTSD coach' intervention in a resource-constrained setting(Stellenbosch : Stellenbosch University, 2023-11-03) Bröcker, Erine; Seedat, Soraya, 1966-; Olff, Miranda; Suliman, Sharain; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Psychiatry.ENGLISH SUMMARY: Posttraumatic stress disorder (PTSD) is a prevalent and impairing mental health condition. Resource-constrained settings face barriers to health care, with individuals not able to access the needed support services. Internet- and mobile-based interventions (IMIs), such as the freely available PTSD Coach mobile application (app), may improve access to and efficiency of care in these settings. The conceptualisation of this doctoral study is based on the high incidence of trauma exposure, PTSD, and its associated sequelae in South Africa exacerbated by healthcare resource constraints. Our overarching aim was to evaluate the feasibility and effectiveness of a four-session counsellor-supported PTSD Coach (PTSD Coach-CS) mobile app intervention in reducing PTSD, depression, anxiety, and stress symptoms in a South African adult community sample. A systematic review and meta-analysis of the PTSD Coach intervention (both webbased and mobile app platforms) supported the feasibility and acceptability of the intervention. Yet, more evidence about the intervention’s effectiveness in lower-middle-income countries, and in larger and more diverse samples, is required. We conducted two pilot studies to evaluate and compare the feasibility, acceptability, and preliminary effectiveness of a counsellor-supported PTSD Coach intervention (web-based compared to the mobile app) in a South African resource-constrained context. The aim of these pilot studies was to shed light on which platform is more feasible and to inform the final procedures of the main study (randomised controlled trial). Findings indicated a clinically significant change in clinician-monitored PTSD symptom severity. However, the counsellor supported PTSD Coach (PTSD Coach-CS) mobile app intervention (compared to the supported web-based PTSD Coach Online) proved to be more feasible in our setting. Both pilot studies supported the involvement of counsellors, as less-specialised mental health services, in intervention delivery as feasible and beneficial in the South African context. The main study (N = 62; female = 89%; black = 77%; aged 19-61 years) indicated a significant reduction in clinician-monitored PTSD symptom severity (primary outcome) over time for the PTSD Coach-CS group compared to the enhanced Treatment-as-Usual group. However, due to the study being underpowered, we could not establish the superiority of the PTSD Coach-CS intervention at post-treatment. The main effect was predominantly driven by significant between-group differences at three-month follow-up. This may point toward a potential lag in intervention effect and/or the benefit of longitudinal engagement with the app on greater symptom reduction over time. We found a significant effect on self-reported stress symptom reduction over time, at post-treatment, and at three-month follow-up. This supports the possibility of longer-term app engagement and a delayed intervention effect on PTSD symptoms mediated through reduced general stress symptoms. Moreover, findings further supported the notion of involving counsellors in intervention delivery as beneficial. A qualitative sub-study, exploring participants’ experience with the PTSD Coach-CS intervention, indicated they were positive about it. Participants valued the counsellor's support, who enabled a practical, effective introduction to and increased engagement with the app. Participants provided insight into intervention-specific and systemic barriers which could increase the value of the PTSD Coach-CS intervention in the South African context. Our study is the first to evaluate the PTSD Coach mobile app intervention in a resource-constrained setting, supplemented with less-specialised mental health services, and contributes to the growing research on IMIs. Our findings underscore that a low-cost counsellor-supported PTSD Coach mobile app intervention is a suitable and potentially effective treatment alternative for adults with PTSD in a resource-constrained setting. This intervention can support trauma survivors and mitigate the burden on the already debilitated healthcare system.
- ItemInvestigation of the potential beneficial effects of cannabidiol on oro-bucco-lingual dyskinesias, oxidative stress and psychosis using animal studies(Stellenbosch : Stellenbosch University, 2022-12) Kajero, Jaiyeola Abiola; Seedat, Soraya, 1966-; Ohaeri, Jude U.; Akindele, Abidemi; Aina, Oluwagbemiga; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Psychiatry.ENGLISH SUMMARY: Background: Oxidative stress is involved in the pathophysiology of schizophrenia and side effects of conventional and atypical antipsychotics such as tardive dyskinesia (TD), weight gain, hyperglycaemia, and hyperlipidaemia. Cannabidiol (CBD) is a potent anti-oxidative and anti-inflammatory agent that also protects against glutamate neurotoxicity. This study’s main objective was to determine if treatment with CBD would attenuate these medications-induced side effects and symptoms of psychosis using a rat model of TD and psychosis. Methods: A total of 206 rats (n=7-10) was used in this study which was conducted in five stages comprising 26 groups. In the first sets of experiments (subchronic haloperidol 5 mg/kg/oral groups of experiments), six experimental groups were given different combinations of oral cannabidiol with 5 mg/kg/oral of haloperidol. In the second and third sets of experiments (subchronic haloperidol 5 mg/kg/i.p. and chronic haloperidol 50mg/kg/i.m. groups of experiments), haloperidol was administered either sub-chronically via the intraperitoneal (IP) route or chronically via the intramuscular (IM) route to six experimental groups, either alone or in combination with CBD. In the fourth sets of experiments (subchronic risperidone 10 mg/kg/oral groups of experiments), six experimental groups were administered oral risperidone (10 mg/kg) either alone or with oral CBD (5 mg/kg) administered before or after risperidone or concomitantly with risperidone. In the fifth sets of experiments (social isolation experiments), Wistar rats were randomly allocated to either socially isolated groups or socially reared groups with or without pharmacological interventions. Weight and fasting blood sugar (FBS) were measured for all groups. Vacuous chewing movement (VCM), anxiety-like behaviour, locomotor activity, cognition, and coordination were assessed at different time points after the last dose of medication in stages one to four of the study. At the end of the isolation period in the social isolation groups of experiments, the Sociability apparatus (3-chambered social test) was used to assess sociability, locomotion, and social novelty preference. Blood for the oxidative stress assay was collected before the animals were sacrificed. The brain, liver, and kidney were harvested after the animals were sacrificed and derived homogenates were used for oxidative stress parameter assays. Results: In the subchronic haloperidol 5 mg/kg/oral groups of experiments, CBD co-administration with haloperidol attenuated VCM and poor motor coordination produced by haloperidol. CBD also ameliorated haloperidol-induced increased blood glucose levels. CBD only at 5 mg/kg appeared to have anxiolytic properties, but may not be as effective as haloperidol, which exhibited a greater anxiolytic effect at 5 mg/kg. Treatment with CBD only at 5 mg/kg also appeared to enhance brain 1,1-Diphenyl-2-Picrylhydrazyl (DPPH) scavenging activity. In the subchronic haloperidol 5 mg/kg/i.p. and chronic haloperidol 50 mg/kg/i.m. groups of experiments, oral CBD (5 mg/kg) attenuated the VCM produced by sub-chronic (IP) haloperidol (5 mg/kg) but had minimal effects on the VCM produced by chronic (IM) administration of haloperidol (50 mg/kg). In both sub-chronic (IP) and chronic (IM) haloperidol groups, there were significant changes in brain, liver and kidney oxidative stress parameters compared with the CBD and control groups. In the subchronic risperidone 10 mg/kg/oral groups of experiments oral CBD (5 mg/kg) significantly reduced risperidone-induced elevated FBS. Oral CBD also attenuated risperidone-induced poor motor coordination but did not have significant effects on VCM, cognition and locomotion. Both CBD and risperidone increased the activity of antioxidant enzymes and decreased the activity of pro-oxidant enzymes. In the social isolation experiments, social isolation affected the locomotor activity of the animals suggesting social isolation induced anxiety. However, CBD did not relieve the social isolation-induced anxiety. Social isolation also increased nitric oxide (NO) activity, reduced glutathione (GSH) levels and reduced CAT activity in the brain, all of which were ameliorated by CBD. Social isolation was associated with a reduction in NO production in the kidney which was reversed by CBD. Conclusion: CBD ameliorated motor impairments produced by haloperidol. Data from this study suggests that CBD can be combined with haloperidol to prevent the emergence of extrapyramidal side effects such as TD. The duration of haloperidol administration also affected the effects of CBD on VCM, and oxidative stress induced by haloperidol. CBD also stabilised FBS and improved motor incoordination induced by haloperidol and risperidone. Both CBD and risperidone exhibited antioxidant properties in the brain. CBD did not improve social cognition or social anxiety but ameliorated social isolation-induced oxidative stress.
- ItemExamining 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.
- ItemShared pleasure in early infant interactions(Stellenbosch : Stellenbosch University, 2022-12) Lachman, Anusha; Niehaus, Dana J. H.; Puura, Kaija; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Psychiatry.ENGLISH SUMMARY: Infant mental health is strongly connected to the quality of caregiving relationships, specifically to the mutual adaptation of the infant and caregiver. Positive shared emotions in infant–caregiver relationships build social, intellectual and psychological resources for the infant, which facilitates optimal growth and development. Sharing positive affect fuels the organisation of early infant experiences of socialisation, and the mother–infant interaction may constitute the first environmental context to shape these abilities. Synchronised behaviours (such as mutual gaze and gaze following) between mothers and their infants are thought to create the foundation of early social connectedness and regulation. Infants are extremely sensitive to the emotional states of their mothers and shared joy is the goal for which mother and child instinctively strive. Shared pleasure (SP) moments in parent–infant interaction are defined as “the parent and the child sharing positive affect in synchrony”. This is expressed in facial expressions, such as a laugh or curving of mouth to smile, together with a direct gaze contact, and a simultaneous or synchronised beginning and ending. SP sequences are analysed from free play video recordings of mother–infant interaction situations by coding the occurrence and duration of moments, including shared eye contact and mutual, synchronous smile or laughter. Shared pleasure is considered a marker of more regulated emotions and, when absent, serves as a possible screening marker for early identification of at-risk dyads. This original study of SP in South Africa focused on mothers and their young infants in a clinical and community setting. The aims of the study were to determine the frequency and duration of SP moments in infants born to mothers with and without mental illness, to correlate SP moments with the Bayley scales of infant toddler development and to determine the presence of sustained infant withdrawal as assessed by the Alarm Distress Baby (ADBB) meausurement of infant withdrawal. The first two studies (Maternal and Infant Mental health study, n = 91) showed an overall low occurrence of SP moments (20%) in the clinical sample, although significantly more SP moments (p = 0.02) were recorded in mothers with no mental illnesses. When infants were screened for withdrawal behaviours measured by a validated tool (the Alarm Distress Baby Scale), there was a significant correlation between low occurrence of SP and higher rates of Infant withdrawal (p = 0.0002). Interestingly, in this sample of high-risk infants, those who experienced SP moments with their mothers at 6 months showed an improvement in cognitive (p = 0.052) and motor (0.007) scores at 18 months. While overall cognitive improvements were noted across the sample, further regression modelling showed stronger associations for the presence of SP moments. Additionally, having an SP moment resulted in a smaller decrease in later motor scores compared with those without an SP moment. Results of the third Drakenstein Child Health Study of SP in the community-based sample of 291 infants and mothers showed a much higher occurrence (82%) of SP. There were no associations with SP and any risk factors, including on- screens of substance use, intimate partner violence, or postpartum depression. The high frequency of SP in a sample of high exposure to risk factors may suggest that SP in reciprocal interactions may only be disrupted in extreme cases(such as severe mental illness) and so may serve as an early red flag for screening if absent early in the interaction. A significant positive quality of the mother–infant relationship and parenting capacity has potential to contribute to favourable child development, especially in mothers at risk of mental illnesses. SP as demonstrated in this study may likely be one of those protective contributors. In a lower- and middle income country such as South Africa, it is important to recognise and screen early for relational difficulties between infant and caregivers, and SP may be considered as a potential screening tool for early, culturally appropriate social connectedness.
- ItemThe 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.