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Background Childhood trauma (CT) has been associated with development of substance use disorders (SUDs) and severe mental illness (SMI) in community cohorts. There is a paucity of data on correlates of CT in dually diagnosed clinical populations in South Africa. We investigated the association among mono-substance use, polysubstance use and CT. Additionally, we explored demographic and clinical correlates of CT. Study aims We investigated associations between CT and SUD in patients with SMI. Setting Participants included patients aged 18–59 years with psychotic disorders attending specialist psychiatric hospital. Methods A cross-sectional study was conducted and the structured clinical interview for DSM-IV, (SCID – I) to determine SUD and SMI, and the childhood trauma questionnaire (CTQ) to measure CT were administered. Results Of the 74 patients, the mean age was 29 years (SD = 8.6) and 64% were male; 64% had schizophrenia-spectrum diagnoses, 23% had BMD-I and 14% had SIPD. Of the patients, 41% were taking no drugs, 22% were mono-drug users and 38% were poly-drug users. There was no significant difference between substance use groups in terms of age or level of education. However, those with no SUDs were significantly more likely to be female, whereas those with mono- or-poly-substance use were significantly more likely to be male. Patients with poly-SUD were significantly less likely to have been married and significantly more likely to have had a diagnosis of SIPD. There were no significant differences in CTQ scores by SUD groups. In this sample of patients with SMI, we found no significant association between CT and SUDs. Conclusion More research is needed into the effects CT has on dual diagnoses to inform treatment approaches to explore traumatic experiences.

Intimate partner violence (IPV) constitutes a major global health problem, affecting one in three women worldwide at some point during their life. IPV is particularly high in low and middle income countries (LMICs) and is associated with a wide range of adverse maternal and child health outcomes. Despite evidence that exposure to IPV affects child development and growth at birth and in infancy, there are limitations to our existing knowledge. First, few studies have considered the impact of maternal emotional IPV separately on child outcomes investigated, focusing primarily on physical and/or sexual IPV. Second, much of the existing data derives from high income countries, rather than from LMIC settings, where the majority of the world's child population lives and where many children are exposed to disproportionately high levels of poverty and violence-related risk factors. Third, there is limited information from well characterized longitudinal studies in these settings and a lack of investigation of associations in very young children, despite the fact that children under 2 years may be particularly at risk for long-term health sequelae relating to IPV exposure. Lastly, few studies have formally investigated potential mediators, inclusive of both behavioral and biological mechanisms underlying associations between IPV and food security and early-life child growth or development. In high-risk settings such as South Africa it is critical to gain improved understanding of pathways by which violence affects child health. This may be especially important given that LMIC contexts often have fewer programs in place to address IPV, and that associated mental health issues and risk factors may be different than in higher income countries. This thesis aimed to investigate IPV in a South African birth cohort, the Drakenstein Child Health Cohort, to understand better the patterns of IPV amongst pregnant and postpartum women, the impact antenatal and postnatal IPV exposure may have on their child's growth and development, and the pathways by which IPV may impact child health sequelae. Chapter 1 reviews the relevant literature, discusses key gaps and presents thesis aims and structure. Chapter 2 comprises a methods chapter which provides an overview of the study population, measures and ethical considerations. Chapter 3 (Paper 1) presents longitudinal profiles of maternal IPV exposure by sub-type from pregnancy through 24 months post-partum and associations between maternal childhood maltreatment and longitudinal frequency and severity of IPV. Chapter 4 (Paper 2) investigates the association between maternal childhood trauma as well as IPV and food insecurity among pregnant women, and examines whether maternal depression mediates these relationships. Chapter 5 (Paper 3) investigates associations between IPV sub-types and growth at birth and 12 months. Further, multiple psychosocial (substance use, depression) and clinical factors (number of hospitalizations) are tested to determine whether any of these may be mediators in the relationship between IPV and child growth. Chapter 6 (Paper 4) investigates emotional, physical and sexual IPV and their relationship with child development at 24 months of age, and whether depression or maternal alcohol dependence mediates these relationships. Chapter 7 presents a summary of findings across results chapters and includes recommendations for future policy and research. Key findings in this population show that: i) a high proportion of mothers are exposed to chronic IPV during and after pregnancy and that maternal childhood abuse or neglect is associated with higher frequency and severity of IPV exposure; ii) maternal IPV and childhood trauma are each associated with food insecurity during pregnancy and that depression partially explains these relationships; iii) emotional and physical IPV are associated with reduced fetal growth and reduced growth through infancy, and maternal substance use (alcohol or tobacco) partially explains these relationships; iv) both emotional and physical IPV are associated with poorer child development at 2 years, and neither maternal current depression nor alcohol dependence explain these relationships. Overall, the findings highlight that emotional IPV in addition to physical IPV is a key risk factor for child growth and development, and identify potential pathways underlying explored relationships. Maternal depression and substance use emerged as partial explanatory variables for nutritional outcomes, specifically food insecurity during pregnancy and growth outcomes at birth and through infancy. The high prevalence of IPV and its negative impact on child health, together comprise a major public health problem, causing significant hardship and representing a significant burden for families, economies and health systems. Findings presented in this thesis suggest that comprehensive and intersectoral programs are needed to 5 address IPV and associated adverse child health outcomes, inclusive of efforts to address maternal mental health and substance use. Further, it is also vital to ensure emotional IPV is included in training and intervention efforts. Clinical implications and areas for future research are discussed.

Introduction: Cognitive impairment is the most significant predictor of long-term outcomes in psychotic disorders, and neuropsychological assessment is therefore recommended in first-episode psychosis patients. However, the literature on neuropsychological assessment for first-episode psychosis patients in low resource settings is limited, the clinical utility of such assessments are unclear, and lengthy assessments may not be practicable in these contexts. This thesis therefore investigated 1) which brief neuropsychological assessment measures researched in patients with psychotic disorders from low and middle-income countries are appropriate for cognitive screening, 2) the differences in prevalence and profile of cognitive impairment between first-episode psychosis patients and healthy peers in one low resource setting, 3) the association of clinical variables with impairment in different cognitive domains in first-episode psychosis patients from one low resource setting, and 4) the validity of the NeuroScreen (a collection of brief neuropsychological test delivered via smartphone) for neuropsychological assessment in first-episode psychosis patients in this setting (as determined by comparison with a gold standard evaluation). Methods: First, a systematic review of articles in which brief neuropsychological assessments were researched in patients with psychotic disorders from low and middle-income countries was performed. The 2014 Working Group on Screening and Assessment (WGSA) guidelines were used as a benchmark of the appropriateness for cognitive screening for the neuropsychological assessment measures employed. Second, first-episode psychosis patients and matched healthy peers were recruited into an observational study at the National mental referral hospital in Uganda. Clinical variables were collated (including sociodemographic characteristics, dietary history, previous childhood trauma and illness severity), and after the resolution of psychotic symptoms, a neuropsychological assessment was performed using the gold standard MATRICS consensus cognitive battery. Student t-tests and chi-square tests were used to determine differences in the prevalence and profile of cognitive impairment in patients with psychosis and healthy peers. Multiple linear regression analyses were used to determined associations between clinical variables and cognitive domains while controlling for potential confounders. Finally, Pearson's rank correlation coefficients and receiver operating curves were computed to examine the validity of the NeuroScreen against the MATRICS consensus cognitive battery. Results: In the 29 articles reviewed, none of the neuropsychological measures researched in patients with psychotic disorders of low and middle-income countries was appropriate for cognitive screening according to the Working Group on Screening and Assessment (WGSA) guidelines. Neuropsychological assessment with the MATRICS consensus cognitive battery found the burden of cognitive impairment in first-episode psychosis patients six times that of healthy peers. The largest cognitive impairment burden was in the visual learning and memory domain. Increased age was associated with impairment in the domains of the speed of processing (p= 0.001). . Cassava rich diets had a negative association with cognitive impairment in the visual learning and memory domain (p=0.04). There were no significant associations between sex, history of childhood trauma or illness severity with any of the seven cognitive domains. A composite score from five cognitive domains of the NeuroScreen had a moderate accuracy of 0.79 compared to the MATRICS consensus cognitive battery. Conclusion: There is need for further research on appropriate measures for neuropsychological assessment in low resource settings. As demonstrated here, the use of such assessments may reveal modifiable risk factors for such impairment; appropriate nutrition may be a particularly important intervention for individuals with psychotic disorders in poorly resourced settings. The NeuroScreen may be useful for neuropsychological assessment of patients with psychotic disorders in low resource settings but needs modification to improve its accuracy.

Background: The frontal lobe of the human brain is integral in regulating behaviour. Behavioural disturbances such as apathy, disinhibition, and dysexecutive function are well-known consequences of frontal lobe pathology, leading to significant impairment. Heavy episodic drinking (HED) and HIV are common conditions that impair the frontal lobe, with disinhibition frequently being seen in people with HED, apathy in HIV positive patients and both HIV and HED leading to executive dysfunction. There is a paucity of research on the interplay between HIV and HED and how this impacts behaviour associated with frontal lobe dysfunction. The Frontal Systems Behaviour Scale (FrSBe) is a questionnaire designed to measure problematic behaviour associated with frontal systems impairment. It has been used in a range of clinical populations. It consists of a total score and three subscale scores, namely apathy (Scale A), disinhibition (Scale D) and executive dysfunction (Scale E). This tool is easy to administer and has the potential to provide clinically useful information that could guide management of patients with these conditions. Aim: As a first step to knowing more about the complex interplay between HIV and HED and its effects on frontal lobe function, the aim of this study was to determine the relationship between HIV status, HED and frontal-systems behavioural dysfunction (impulsivity, apathy, and executive dysfunction) as measured by the FrSBe. Methods: Participants for this quantitative, cross-sectional, and analytical study were recruited from the Nolungile Clinic in Khayelitsha, Cape Town. They were grouped according to their HIV- and HED status. Relevant demographic and clinical data were obtained. Participants completed the Substance Abuse and Mental Illness Symptoms Screener (SAMISS) questionnaires and the FrSBe self-report measure that was translated into isiXhosa. Both measures were scored and the FrSBe raw scores were converted to T-scores. Results: A total of the 99 participants met the inclusion criteria, of which 25 were in the HED only group, 22 in the HIV+ only group, 26 in the dual group, and 26 were in the control group. The mean age (SD) of the sample was 37.92 (8.8) years. There was a statistical difference between groups for the total drinking score on the SAMISS (p = 65), were present on the FrSBe Total Score in 29 of the participants. On the apathy subscale score, 36 participants had clinically significant (T-score >= 65) deficits, 14 had deficits on the disinhibition subscale, and 34 had on the executive dysfunction subscale. There were no statistically significant differences in the proportion of participants with clinically significant deficits between groups for any FrSBe scores. Conclusions: This study shows that people with HED have more dysfunctional behaviour associated with frontal system impairment and are more disinhibited. HIV status does not appear to influence frontal system behaviour. These finding needs to be interpreted with caution as the study FrSBe was administered in isiXhosa, in which it has not been validated, and no normative data was available for the study population. Future studies validating the FrSBe in a South African context and deriving normative data for South African populations would be a first step into developing the FrSBe into a clinically useful tool. This could, in turn, potentially lead to improved care and treatment in these conditions by identifying specific impairments and problematic behaviours as targets for intervention.

Mental disorders are highly prevalent and represent an increasingly important public health priority in Canada and globally. Extensive research suggests that exposure to prenatal maternal stress can negatively impact offspring neurodevelopment and mental health. However, the factors that influence the development of mental disorders are varied, and do not occur in isolation. As a result, ascertaining which variables may drive or influence the associations between prenatal stress and mental disorders in children is particularly important, given the substantial burden that is attributed to poor mental health. The overarching aim of this doctoral thesis is to examine how biological and psychosocial factors influence the relationships between prenatal maternal stress and children’s mental health outcomes. Four longitudinal studies were conducted to address this aim, using data from three international prospective birth cohort studies. Analyses comprised of structural equation modelling techniques, including latent moderated structural equation models and mediation analyses. The first two studies utilized data from a Norwegian birth cohort study to examine how parenting and maternal positive mental health, respectively, modified the associations between prenatal maternal stress and children’s internalizing and externalizing symptoms. Broadly, these results demonstrated that positive influences attenuated the associations between prenatal maternal stress and children’s internalizing and externalizing symptoms, whereas negative influences strengthened the associations. The final two studies utilized data from Dutch and British birth cohorts. These studies sought to examine whether maternal and child inflammatory marker concentrations mediated the associations between prenatal maternal stress and children’s mental health outcomes. There was no significant mediation through maternal levels of C-reactive protein during pregnancy, however, the association between prenatal maternal stress and generalized anxiety disorder in adolescence was mediated by children’s levels of interleukin-6. Prenatal maternal stress was consistently associated with children’s mental health across all four studies. This doctoral thesis has identified several important factors that influence the associations between prenatal maternal stress and children’s mental health. Findings can serve to facilitate further research in this area, and ultimately, impact both health policy and clinical practice by stimulating the provision of tailored prevention and intervention efforts that may potentially reduce the burden of poor mental health.

Background Mental disorders including substance use disorders are a leading cause of disease burden, contributing 16% of the global burden of disease in young people aged 10 to 19 years. Substance use in adolescents and young people cannot be viewed outside of the family system. The family may influence the development of substance use problems in young people and the family system is an important part of recovery. The burden of substance use on family members is, however, often overlooked with emphasis being placed on the need to involve families in treatment of individuals using substances but little said about care for the family members themselves. There is need for a better understanding of the experiences of family members affected by substance use in young people and their own perceptions of the family's role in influencing adolescents' substance use. This study aimed to explore the experiences of families who have dealt with adolescent psychoactive substance use and their perceptions on how families can influence the development or avoidance of substance use in young people. Methods This was an exploratory qualitative study eliciting the experiences of nineteen family members dealing with substance use in young people aged less than 24 years purposively sampled from families of young people being managed for substance-related conditions at a tertiary mental health unit in Harare, Zimbabwe. Potential participants were identified using admission and outpatient registers and invited to take part in the study. In-depth interviews were conducted in Shona or English using a semi-structured interview guide exploring the experiences of family members dealing with substance use in a young person as well as their perceptions on the role of the family in development of substance use. The interviews were voice recorded, transcribed verbatim and the data were analysed in NVivo 12 using the framework approach. Ethical approval was granted from the University of Cape Town, Faculty of Health Sciences Human Research Ethics Committee and the Medical Research Council of Zimbabwe and the Institutional Ethics Review Boards for Harare Central Hospital. Results Five themes emerged from the data namely: Perceived causes of substance use in young people; Discovery of the substance use; Impact of the substance use; Family coping strategies and Family suggested interventions. Substance use by a young person affected family life, affecting family members and siblings emotionally, causing conflict in the family and burdening the family finances. Family members struggled with physical health problems; emotional distress, fear; helplessness; hopelessness; guilty, stigma and isolation, social and occupational consequences as a result of substance use by a young person in the family. Families also described various ways in which they attempted to cope with the challenges with spirituality highlighted as a key coping strategy. Participants suggested the family can be a mitigating factor against substance use in young people through having a better understanding about substance use, improved communication; providing an emotionally supportive home environment; creating healthier value systems in the family; actively supervising and monitoring of young people; encouraging young people to engage in meaningful work; facilitating admission for medical rehabilitation when needed as well as providing spiritual support. Conclusion There is a substantial but hidden burden of substance use on families and caregivers. This study illustrates the need for health services to provide better support for affected families, improving access to care and support for family members of young people using substances at risky levels. Further research is needed to explore how existing frameworks for structured support may be adapted for and implemented in the local setting. Substance use, particularly in young people, remains a family condition and the family needs to be not only included in treatment of young people but to be cared for themselves as well.

Introduction Information on the relationship between cigarette use and recovery from substance use disorders (SUDs) is contradictory and limited to studies conducted in high-income countries characterised by a predominance of injection drug use. In South Africa, a low-and-middleincome country where drugs are mainly smoked, there is an absence of research examining the relationship between smoking and SUD treatment outcomes. This study seeks to bridge this gap by exploring service users' perceptions of smoking and how cigarette use affects their recovery from SUDs. Methods This exploratory study employed a qualitative research design. Twenty participants were recruited from six Matrix Outpatient SUD treatment programmes in the greater Cape Town region for in-depth interviews. A semi-structured interview guide structured the interviews. Interviews were audio-recorded before being transcribed verbatim. Qualitative data were analysed using the framework approach. Results Three main findings emerged from the data. First, powerful socio-cultural and contextual factors seem to underpin participants early initiation and maintenance of cigarette use. Participants identified socio-cultural processes that strongly influenced their perceptions of smoking and the social and emotional functions it served, which contributed to continued cigarette use. Second, participants described the intertwining of cigarettes and other substances, with shared modes of administration and mixing of substances - they thought this made it very challenging to maintain recovery from substances while continuing to smoke tobacco. Third, although service users perceive benefits to tobacco cessation for health and recovery from SUDs, most participants using tobacco expressed ambivalence about quitting and seem to lack confidence in their ability to stop smoking and maintain their abstinence from other substances. Conclusion The current study suggests that SUD service users view cigarette use as potentially detrimental to their SUD treatment and recovery. As such, this study provides support, from a service user perspective, for (i) the introduction of interventions to prevent tobacco initiation among young people as part of SUD prevention and (ii) the integration of tobacco cessation interventions into SUD treatment programming to improve the likelihood of successful treatment outcomes for people who smoke tobacco. More specifically, findings highlight the potential value of a client-centred approach in screening service users for tobacco use as they enter SUD treatment, educating them about the potential impacts of continued smoking on SUD recovery, and integrating evidence-based smoking cessation programmes into SUD treatment.

Background. Common mental disorders (CMDs), including depression and anxiety disorders, and risky alcohol use are highly prevalent among people living with HIV. Yet, many studies have found that most people who suffer from mental disorders do not receive treatment, especially in low-income countries. Given people living with HIV frequent health services, this represents a missed opportunity for identification and treatment that could improve physical and mental health outcomes. The aim of this study was to identify missed opportunities to address mental health of people living with HIV in Malawi. Four types of missed opportunities were operationalised for this study. The first two address missed opportunities for screening or identification For missed opportunity #1, a respondent had to screen positive for mental health problem (depression/anxiety or alcohol use ; and in any of their visits to the clinic in the past 12 months, the clinical officer or nurse did not ask about their mental health. Missed opportunity definition #2 was a more nuanced missed opportunity for identification of probable mental health problems. A respondent had to be undetected for mental health problems; and in any of his or her visits to the clinic in the past 12 months, the clinical officer or nurse did not ask about his or her mental health and s/he wanted to receive advice or treatment about his or her mental health problems. The second to definitions address missed opportunities for treatment. For missed opportunity definition #3, a respondent had to screen positive for mental health problem and if in any of his or her visits to the clinic in the past 12 months, and s/he did not receive advice or treatment. For missed opportunity definition #4, a more nuanced missed opportunity for the treatment of probable mental health problem: a respondent had to screen positive for a mental health problem; s/he wanted to receive advice or treatment about his or her mental health problems/alcohol use; and in any of their visits to the clinic in the past 12 months, s/he did not receive treatment for a mental disorder/risky alcohol use. Methods. A a random of participants receiving HIV care were approached while they were waiting for their consultation at three ART clinics namely: Tisungane, Matawale and Domasi. Those who consented to participants were interviewed in a private room. The Self-Reporting Questionnaire-20 (SRQ-20) and the Alcohol Use Disorders Identification Test (AUDIT) were used to detect probable cases of CMDs and clients consuming alcohol at risky levels. Following v administration of the SRQ-20 and AUDIT, participants were asked if clinical officers (COs) or nurses inquired about their feelings (sad or worried) or alcohol consumption during their routine visits to ART clinics, thus eliciting data on identification by healthcare workers or identification of CMD symptoms. The participants were also asked whether advice or treatment was recommended and whether they would have liked to receive advice or treatment regarding their feelings or risky alcohol use. Descriptive statistics were utilized to calculate prevalence estimates of missed opportunities and multiple logistic regression models were used to determine the factors associated with missed opportunities for mental health service provision. Results. The study had 382 participants. The proportion of participants who screened at risk was 77 (20.2%) for probable CMDs and 16 (4.2%) for risky alcohol use. The proportion of participants who screened at risk for any mental health problem (depression, anxiety and risky alcohol use) was 87 (22.8%). Participants who were asked by clinical officers and nurses about CMD symptoms and alcohol use were 92 (24.1%) and 89 (23.3%) respectively. Of the entire sample, 351 (91.9%) participants wanted to receive advice or treatment and 26 (29.9%) received advice or treatment. Missed opportunities to address the mental health of people living with HIV were found to be as follows: definition #1, 40 participants (46.0%); definition #2, 35 participants (40.2%); definition #3, 87 participants (100%) and definition #4, 66 participants (75.9%). After adjusting for other variables in the model female gender was significantly associated with missed opportunity definition #1. After adjusting for other variables in the model female participants were more likely to meet criteria for missed opportunity definition #2 than male participants. Furthermore, older participants were less likely to meet criteria for missed opportunity definition #2 compared to younger participants. Participants who were employed were less likely to meet criteria for missed opportunity definition #2. In the same vein, participants who were spending less were less likely to meet criteria for missed opportunity definition #2. Given all participants met criteria, we were unable to develop logistic regression models. There were no significant associations for missed opportunity definition #4. Conclusion. Approximately one fifth of the sample recruited screened at risk for CMDs and most clients wanted to receive advice or treatment. Despite over 40% of the participants reporting being asked about CMD symptoms, PHC workers did not provide advice or treatments to 75.9% of clients. There is need to advocate for screening of mental health problems including alcohol use and treatment in all ART clinics in Malawi.

Includes bibliographical references / Introduction: Mental health of Ugandans could be improved through mainstreaming the services into primary care systems. Nurses constitute a high percentage of the workforce in health; therefore they can significantly contribute towards several experiences by patients with mental illness. Stigma towards mental illness and individuals living with mental illness is among the major hindrances to effective mental health service delivery amongst healthcare workers. Therefore it is important for stigma to be explored among general nurses as mental health services are being integrated into the primary health care. The aim of this study was to explore stigma among general nurses towards mental illness and individuals living with mental illness. Methods: This was a cross-sectional quantitative study. Self-administered questionnaires were distributed to nurses working in Amolatar district health facilities that measured knowledge, attitudes and behaviour towards individuals living with mental illness, in addition to their familiarity with a person with mental illness. Descriptive statistics were used to determine the extent to which stigma was reported in this population. Bivariate and multivariate analyses were done using linear and logistic regressions to identify the predictors of the knowledge, attitudes and behaviours of nurses regarding mental illness and individuals living with mental illness. Results: Sixty-three general nurses participated in the study. Most of the participants identified schizophrenia as an SMI, however 79% considered stress to be mental illness and only a quarter of respondents scored above 80% on knowledge about mental illness. Most of the participants believed that psychotherapy was the most effective treatment for mental disorders. The nurses were benevolent (mean 3.06, s.d 0.29) and showed acceptance towards mental health services and individuals living with mental illness in the community (mean 3.56, s.d 0.30) however the nurses tended towards authoritarianism (mean 3.74, s.d 0.34) and social restrictiveness (mean 2.98, s.d 0.27). Level of contact with individuals living with mental illness predicted community mental health ideology and authoritarianism. No demographic variables were associated with level of knowledge using MAKS score and intended behaviour using RIBS tool. Conclusion: This study has provided some of the first data on stigma among primary health care nurses towards people with mental illness in Uganda and has added to knowledge of stigma towards people with mental illness by health care providers in LAMIC. Many of the findings were positive and bode well for the planned integration of mental health in primary health care. The negative findings of this study have shown that there are many areas for improvement which could be tackled by interventions such as public and community education, and in-service training regarding causes and management of mental disorders. Further research could be done to understand more about the negative attitudes found in many LAMIC.