Doctoral Degrees (Psychiatry)

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Shared 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.
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.
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.
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.
Metabolic syndrome risk factor associations with clinical, functional and cognitive outcomes during the first year of treatment in schizophrenia spectrum disorders
(Stellenbosch : Stellenbosch University, 2021-03) Luckhoff, Hilmar Klaus; Emsley, Robin; Du Plessis, Stefan S.; Kilian, Sanja; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Psychiatry.
ENGLISH SUMMARY : Treatment-emergent metabolic syndrome is an established risk factor for cardiovascular disease known to be associated with cognitive impairment, poor functioning and decreased quality of life in schizophrenia spectrum disorders. However, weight gain and increased lipids have also been correlated with clinical improvement in chronic schizophrenia patients. While most studies investigating the relationships between body mass and treatment outcome were conducted in patients treated with clozapine and olanzapine, it remains unclear to what extent the role of weight gain as a predictor of favourable clinical outcomes extends to include illness-specific symptom domains in first-episode patients treated with other antipsychotics with a lower obesogenic potential. The effects of other clinical (e.g. sex, substance use, baseline body mass) and treatment-related (e.g. antipsychotic dose, medication adherence) confounders on the above relationships is also unclear. In response to these knowledge gaps, the overarching aim of our doctoral studies was to explore the temporal evolution of metabolic syndrome risk factors and their effects on clinical outcome over 12 months of treatment in first-episode schizophrenia spectrum disorder patients. We found that an increase in body mass correlates with global psychopathology improvement as well as the disorganized symptoms domain of schizophrenia in first-episode patients (n=106) over 12 months of treatment, independent of the degree of antipsychotic exposure (sub-study I). The association between weight gain and clinical improvement extended to include better overall end-point cognition after 12 months of treatment in our first-episode patient cohort (n=72) (sub-study II). A differential effect for lower baseline body mass index as a predictor of end-point working memory performance was evident in substance users (unfavourable) compared to their non-using counterparts (favourable). The adverse role of low body mass index as an unfavourable prognostic marker was further substantiated by its associations with an earlier age of psychosis onset and more severe negative symptoms in first-episode patients (n=69) (sub-study III). The inclusion of a diffusion tensor imaging component to our research also revealed a similar differential association of body mass index with fronto-limbic white matter fractional anisotropy (FA) in first-episode patients (low body mass index, low FA) versus healthy controls (high body mass index, low FA) adjusting for age and sex (sub-study III). Extension of our structural neuroimaging research to include brain structures involved in the physiological, hedonic and cognitive control as part of a “core eating network” further identified smaller anterior hippocampal volumes as a sex-specific predictor of weight gain in first-episode patients (n=90) (sub-study IV). Our research supports the role of weight gain as a predictor of favourable clinical outcomes in first-episode schizophrenia patients for whom treatment adherence is assured. In contrast, low body mass and by extension failure to gain weight could represent an unfavourable prognostic marker in first-episode patients, particularly those who use substance users. Future studies would do well to combine clinical, biological and neuroimaging data in order to characterize intrinsic metabolic profiles in relation to long-term treatment outcomes in firstepisode schizophrenia.

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