Browsing by Author "Koen, Nastassja"
Now showing 1 - 6 of 6
Results Per Page
Sort Options
- ItemOpen AccessCardiovascular risk profile of adults with psychotic disorders in Eldoret, Kenya(2020) Kwobah, Edith Wanjiku Kamaru; Stein, Dan J; Atwoli, Lukoye; Koen, NastassjaIntroduction: Cardiovascular disorders contribute significantly to mortality and morbidity amongst patient's psychotic disorders such as schizophrenia and bipolar mood disorders. In addition to conventional risk factors for cardiovascular disorders (smoking, alcohol use, inadequate physical activity, hypertension, diabetes, dyslipidaemia, obesity and metabolic syndrome, and non-modifiable factors such as sex, age and social-economic status) exposure to potentially traumatic events, psychological distress, comorbidity of other medical conditions, and use of antipsychotics may also increase cardiovascular risk in patients with psychosis. There is also evidence to suggest that intervention to mitigate such cardiovascular risk factors are suboptimal, hence contributing to poor outcomes. Despite growing interest in cardiovascular health, there remains a paucity of data on the prevalence of the various cardiovascular risk factors among patients with psychosis in low resource settings such as Sub-Saharan Africa. This is likely to differ from high resource contexts given social-cultural and economic differences as well as differences in the health systems. In order to design contextually relevant cardiovascular risk screening, treatment and prevention guidelines that can be integrated into routine care of the mentally ill patients in low- and middle-income countries (LMICs), further work in this setting is warranted. Objectives: The aim of this thesis was to establish the cardiovascular risk profile among patients treated for psychotic disorders at Moi Teaching and Referral Hospital (MTRH) in Eldoret, Western Kenya. Specific objectives were as follows: 1. To conduct a literature review on the burden and etiological mechanisms of cardiovascular risk in patients with psychosis, with a focus on LMIC. 2. To compare the prevalence, as well as sociodemographic and clinical correlates, of conventional cardiovascular risk factors (smoking, alcohol intake, poor diet, and lack of exercise, diabetes mellitus, hypertension, obesity, dyslipidaemia and metabolic syndrome) in patients with psychosis versus matched controls. 3. To establish the prevalence and correlates of non-conventional risk factors; psychological distress, traumatic events (lifetime and childhood trauma) and comorbid medical disorders in patients with psychosis and controls, and to delineate how these risk factors contribute to the overall cardiovascular risk. 4. To describe current psychopharmacological treatments and explore potential associations with cardiovascular risk among patients with psychosis. 5. To explore the overall 10-year cardiovascular disease risk, as well as the social demographic and clinical correlates among patients and controls. 6 .To determine the proportion of untreated metabolic disorders (hypertension, diabetes mellitus, and dyslipidaemia) in patients with psychotic disorders and matched controls. Methods: This was a cross-sectional descriptive survey comparing 300 patients with psychosis and 300 controls at Moi Teaching and Referral Hospital, Western Kenya. A paper based researcher-administered questionnaire was used to collect data on demographic variables (age, sex, education level, and marital status), and risk factors (smoking, alcohol intake, diet, physical activity). We used the Composite International Diagnostic Interview (CIDI) to assess for presence of other chronic medical disorders. Data on childhood trauma were obtained using the Childhood Trauma Questionnaire (CTQ) while the Life Events Checklist (LEC) was used to obtain data on lifetime exposure to potentially traumatic events. Data on psychological distress among controls were obtained using the Kessler-10 questionnaire. Measurements of weight, height, abdominal circumference and blood pressure were taken from each of the participants. Blood was drawn for measurement of glucose level and lipid profile. Data analysis was undertaken using Stata version 15. T-tests were used to compare continuous variables while Pearson chi-squared tests was used for categorical variables. Regression modelling was undertaken to assess associations between sociodemographic and clinical predictor variables and the cardiovascular risk factors. Results: Data collection took place between July 2018 and March 2019. The mean age of patients was 33 years and of controls was 35 years. Compared to controls, patients were more likely to be unmarried (46% vs 33% p< 0.001), and were reduced among females (OR 0.41 p20). The estimated 10 year cardiovascular risk was significantly associated with female Sex (p=0.007), age (p <0.001), current tobacco smoking (p <0.001) and metabolic syndrome (P<0.001). Among the patients, 280 (94.3%) patients were on antipsychotics with the majority (86.5%) being treated with olanzapine. Of all the participants with diabetes 60% among patients and 22% among controls were not on treatment. Of the total number of participants with hypertension, 65% of patients and 47% controls were not on treatment. Conclusion: In the study setting of Eldoret, Western Kenya, patients with psychosis were found to have high levels of lifestyle cardiovascular risk factors such as smoking, inadequate intake of fruits and vegetables and inadequate physical activity. They were also found to have high rates of metabolic disorders such as hypertension, obesity, metabolic syndrome and dyslipidaemia. There was no evidence of increased cardiovascular risk among participants exposed to traumatic life events, with those experiencing psychological distress or those with other chronic medical disorders. The use of olanzapine was not significantly associated with increased cardiovascular risk in this setting. There was an identifiable gap in the treatment of cardiovascular risk factors in this setting. Given these findings, we recommend efforts to address these risk factors by development of protocols to ensure screening for these risk factors, adequate documentation and appropriate treatment.
- ItemOpen AccessGenetic and epigenetic associations with child development and mental health in a South African birth cohort(2025) Moyakhe, Lihle; Koen, Nastassja; Stein, Dan; Dalvie, ShareefaChildhood developmental and mental disorders – including internalising and externalising symptoms – are prevalent in low- and middle-income countries (LMICs) such as South Africa. There is growing interest in the associations between polygenic risk scores (PRS), epigenetic age (EA) deviation, DNA methylation risk scores (MRS), and key neurodevelopmental disorders such as attention-deficit hyperactivity disorder (ADHD). However, most work has thus far been undertaken in high-income countries (HICs) with participants of European ancestry; and populations of African ancestry have been notably under-represented. The Drakenstein Child Health Study (DCHS), an ongoing South African birth cohort study, provides an opportunity to investigate the associations of PRS, EA deviation, and MRS, with childhood developmental and mental health outcomes, in an ancestrally diverse study population. This doctoral project aimed to investigate potential genetic and epigenetic associations with adverse developmental and mental outcomes in children. This aim was addressed via five objectives. First, a systematic review was undertaken to collate existing work (both in HICs and LMICs) on associations between PRS (the weighted sum of risk alleles) and developmental and mental health disorders in childhood and adolescence. A second systematic review focused on associations between EA deviation (relative to chronological age) and the outcomes of interest. Third, empirical analyses of DCHS data investigated the relationship between a PRS for ADHD, and child developmental outcomes, as well as internalising and externalising symptoms. Fourth, the relationship between gestational EA deviation at birth, and child developmental and mental health outcomes in the DCHS, was explored. Finally, the association between MRS (the weighted sum of methylation markers' beta values) at birth, and the outcomes of interest, was investigated. The systematic reviews adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, and standard methods were used to collate and analyse the data. In the DCHS, a PRS for ADHD was generated (target n=958) using summary statistics from the Early Genetics and Lifecourse Epidemiology (EAGLE) consortium (discovery n=17,666). Gestational EA deviation at birth and MRS were calculated using DCHS umbilical cord blood samples (n=275) and summary statistics from the Pregnancy and Childhood Epigenetics (PACE) consortium (n=2,477 for the MRS analyses). Child developmental outcomes (i.e. cognitive, language and motor development) were derived from the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III), and child mental health outcomes (i.e. internalising and externalising symptoms) from the Child Behaviour Checklist (CBCL). Associations of interest were investigated using bivariate and multivariable linear and logistic regression models, controlling for relevant covariates (including sociodemographic characteristics, psychosocial risk factors, child anthropometric measures and genomic principal components). In the first systematic review (of 14 studies, with ~50,000 participants), significant associations between PRS for several mental health disorders and adverse developmental/mental health outcomes were found. For example, a high ADHD PRS was found to be associated with adverse outcomes in childhood and adolescence in 5 of the 14 included studies. Additionally, 4 studies described associations between PRS for bipolar disorder and impaired cognitive function, and poor executive functioning, in children and adolescents; and 2 studies highlighted associations between schizophrenia PRS and ADHD, as well as internalising and externalising symptoms in children. In the second systematic review (of 4 studies with N~700 participants), gestational EA acceleration was found to be significantly associated with internalising symptoms in children. The empirical analyses yielded no significant genetic or epigenetic associations with the developmental or mental health outcomes of interest in the DCHS children. However, trend-level associations were observed - in both the unadjusted and the adjusted models - between gestational EA deviation at birth and child externalising symptoms (at 42 months) in the DCHS (unadjusted β = −0.19, p = 0.072; adjusted β = -0.17, p= 0.10). While limited by sample size and lack of ancestry-matched summary statistics, this work nonetheless represents a novel exploration of the potential genetic and epigenetic underpinnings of developmental and mental disorders in South African children. In future, further studies – ideally with larger sample sizes, ancestry-matched summary statistics and longitudinal developmental phenotype data – would be warranted to expand on this preliminary work. Ultimately, such research may provide insight into the genetic and epigenetic risk factors of developmental and mental health outcomes in children; and may inform targeted early interventions for at-risk children – particularly in resource-limited settings such as South Africa.
- ItemOpen AccessMaternal blood contamination of collected cord blood can be identified using DNA methylation at three CpGs(BioMed Central, 2017-07-25) Morin, Alexander M; Gatev, Evan; McEwen, Lisa M; MacIsaac, Julia L; Lin, David T S; Koen, Nastassja; Czamara, Darina; Räikkönen, Katri; Zar, Heather J; Koenen, Karestan; Stein, Dan J; Kobor, Michael S; Jones, Meaghan JBackground: Cord blood is a commonly used tissue in environmental, genetic, and epigenetic population studies due to its ready availability and potential to inform on a sensitive period of human development. However, the introduction of maternal blood during labor or cross-contamination during sample collection may complicate downstream analyses. After discovering maternal contamination of cord blood in a cohort study of 150 neonates using Illumina 450K DNA methylation (DNAm) data, we used a combination of linear regression and random forest machine learning to create a DNAm-based screening method. We identified a panel of DNAm sites that could discriminate between contaminated and non-contaminated samples, then designed pyrosequencing assays to pre-screen DNA prior to being assayed on an array. Results: Maternal contamination of cord blood was initially identified by unusual X chromosome DNA methylation patterns in 17 males. We utilized our DNAm panel to detect contaminated male samples and a proportional amount of female samples in the same cohort. We validated our DNAm screening method on an additional 189 sample cohort using both pyrosequencing and DNAm arrays, as well as 9 publically available cord blood 450K data sets. The rate of contamination varied from 0 to 10% within these studies, likely related to collection specific methods. Conclusions: Maternal blood can contaminate cord blood during sample collection at appreciable levels across multiple studies. We have identified a panel of markers that can be used to identify this contamination, either post hoc after DNAm arrays have been completed, or in advance using a targeted technique like pyrosequencing.
- ItemOpen AccessPrevalence of lifestyle cardiovascular risk factors and estimated framingham 10-year risk scores of adults with psychotic disorders compared to controls at a referral hospital in Eldoret, Kenya(2023-12-05) Kwobah, Edith; Koen, Nastassja; Mwangi, Ann; Atwoli, Lukoye; Stein, Dan J.Abstract Introduction Lifestyle factors such as smoking, alcohol use, suboptimal diet, and inadequate physical activity have been associated with increased risk of cardiovascular diseases. There are limited data on these risk factors among patients with psychosis in low- and middle-income countries. Objectives This study aimed to establish the prevalence of lifestyle cardiovascular risk factors, and the 10-year cardiovascular risk scores and associated factors in patients with psychosis compared to controls at Moi Teaching and Referral Hospital in Eldoret, Kenya. Methods A sample of 297 patients with schizophrenia, schizoaffective disorder, or bipolar mood disorder; and 300 controls matched for age and sex were included in this analysis. A study specific researcher-administered questionnaire was used to collect data on demographics, antipsychotic medication use, smoking, alcohol intake, diet, and physical activity. Weight, height, abdominal circumference, and blood pressure were also collected to calculate the Framingham 10-year Cardiovascular Risk Score (FRS), while blood was drawn for measurement of glucose level and lipid profile. Pearson’s chi-squared tests and t-tests were employed to assess differences in cardiovascular risk profiles between patients and controls, and a linear regression model was used to determine predictors of 10-year cardiovascular risk in patients. Results Compared to controls, patients with psychosis were more likely to have smoked in their lifetimes (9.9% vs. 3.3%, p = 0.006) or to be current smokers (13.8% vs. 7%, p = 0.001). Over 97% of patients with psychosis consumed fewer than five servings of fruits and vegetables per week; 78% engaged in fewer than three days of vigorous exercise per week; and 48% sat for more than three hours daily. The estimated 10-year risk of CVD was relatively low in this study: the FRS in patients was 3.16, compared to 2.93 in controls. The estimated 10-year cardiovascular risk in patients was significantly associated with female sex (p = 0.007), older patients (p < 0.001), current tobacco smoking (p < 0.001), and metabolic syndrome (p < 0.001). Conclusion In the setting of Eldoret, there is suboptimal physical exercise and intake of healthy diet among patients with psychosis and controls. While the estimated risk score among patients is relatively low in our study, these data may be useful for informing future studies geared towards informing interventions to promote healthy lifestyles in this population.
- ItemOpen AccessPsychological trauma and posttraumatic stress disorder in a South African birth cohort study(2015) Koen, Nastassja; Stein, Dan J; Ramesar, RajkumarPsychological trauma - including exposure to intimate partner violence (IPV) - is highly prevalent in South Africa, and may result in posttraumatic stress disorder (PTSD) in a subset of individuals. Pregnant women and new mothers are particularly vulnerable; and trauma exposure and PTSD in this sub-group may be associated with a number of adverse maternal-child sequelae including poor birth outcomes and impaired infant neurodevelopment. Risk factors for psychological trauma exposure, and for subsequent PTSD, are likely to include environmental and genetic influences. Given the high burden of trauma and related disorders, the unique genetic ancestry, and the relative paucity of empirical data, further work in South African populations is warranted. This thesis aimed to investigate a number of questions about trauma and PTSD in the Drakenstein Child Health Study (an ongoing South African birth cohort study), including their risk factors, their impact on infant birth anthropometry and development, and their genetic correlations. This thesis includes five publications, all presenting data from the Drakenstein Child Health Study. Pregnant women were recruited from two clinics in the Drakenstein sub-district - a peri-urban community outside Cape Town, Western Cape. Sociodemographic characteristics; psychosocial risk factors (including depression, stressful life events, psychological distress and alcohol and substance misuse); trauma exposure (childhood trauma, IPV and lifetime trauma); and PTSD were assessed using validated and reliable self-reported questionnaires, as well as diagnostic psychiatric interviews.
- ItemOpen AccessThe developmental effects of HIV and alcohol: a comparison of gestational outcomes among babies from South African communities with high prevalence of HIV and alcohol use(BioMed Central, 2017-05-08) Donald, Kirsten A M; Fernandez, Anne; Claborn, Kasey; Kuo, Caroline; Koen, Nastassja; Zar, Heather; Stein, Dan JBackground: There is growing evidence of the negative impact of alcohol on morbidity and mortality of individuals living with HIV but limited evidence of in utero efects of HIV and alcohol on exposure on infants. Methods: We conducted a population-based birth cohort study (N = 667 mother-infant dyads) in South Africa to investigate whether maternal alcohol use and HIV afected gestational outcomes. Descriptive data analysis was conducted for all variables using frequency distributions, measures of central tendency, and estimates of variance. Hierarchical multiple regression was conducted to determine whether maternal alcohol use, maternal HIV status and other risk factors (socioeconomic status, smoking, depression) predicted infant outcomes. Results: Our results showed severity of recent alcohol use and lifetime alcohol use predicted low birth weight. Similarly lifetime alcohol use predicted shorter infant length, smaller head length, smaller head circumference, and early gestational age. However, HIV status was not a signifcant predictor of gestational outcomes. Conclusions: The unexpected fnding that maternal HIV status did not predict any of the gestational outcomes may be due to high rates of ART usage among HIV-infected mothers. The potentially negative efects of HIV on gestational outcomes may have been attenuated by improved maternal health due to high coverage of antiretroviral treatment in South Africa. Interventions are needed to reduce alcohol consumption among pregnant mothers and to support healthy growth and psychosocial development of infants.