Psychological trauma and posttraumatic stress disorder in a South African birth cohort study

Psychological 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

Prevalence 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

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 \u3c 0.001), current tobacco smoking (p \u3c 0.001), and metabolic syndrome (p \u3c 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

The 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

BACKGROUND: 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 effects 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 affected 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 significant predictor of gestational outcomes. CONCLUSIONS: The unexpected finding 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 effects 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

Large scale genetic research on neuropsychiatric disorders in african populations is needed

In recent years there have been significant insights into the complex aetiologies of neurodevelopmental brain disorders. For example, neuropsychiatric genetics has achieved success with the identification of 108 loci for schizophrenia (Schizophrenia Working Group of the Psychiatric Genomics Consortium, 2014). Furthermore, meta-analyses of genomewide association study (GWAS) results encompassing thousands of samples have been completed for other psychiatric disorders including attention-deficit/hyperactivity disorder (ADHD), autis

Risk and protective factors for child development: An observational South African birth cohort.

BACKGROUND: Approximately 250 million (43%) children under the age of 5 years in low- and middle-income countries (LMICs) are failing to meet their developmental potential. Risk factors are recognised to contribute to this loss of human potential. Expanding understanding of the risks that lead to poor outcomes and which protective factors contribute to resilience in children may be critical to improving disparities. METHODS AND FINDINGS: The Drakenstein Child Health Study is a population-based birth cohort in the Western Cape, South Africa. Pregnant women were enrolled between 20 and 28 weeks' gestation from two community clinics from 2012 to 2015; sociodemographic and psychosocial data were collected antenatally. Mothers and children were followed through birth until 2 years of age. Developmental assessments were conducted by trained assessors blinded to background, using the Bayley-III Scales of Infant and Toddler Development (BSID-III), validated for use in South Africa, at 24 months of age. The study assessed all available children at 24 months; however, some children were not able to attend, because of loss to follow-up or unavailability of a caregiver or child at the correct age. Of 1,143 live births, 1,002 were in follow-up at 24 months, and a total of 734 children (73%) had developmental assessments, of which 354 (48.2%) were girls. This sample was characterised by low household employment (n = 183; 24.9%) and household income (n = 287; 39.1% earning 1 domain affected, and 75 (10.2%) had delay in all domains. Bivariate and multivariable analyses revealed several factors that were associated with developmental outcomes. These included protective factors (maternal education, higher birth weight, and socioeconomic status) and risk factors (maternal anaemia in pregnancy, depression or lifetime intimate partner violence, and maternal HIV infection). Boys consistently performed worse than girls (in cognition [β = -0.74; 95% CI -1.46 to -0.03, p = 0.042], receptive language [β = -1.10; 95% CI -1.70 to -0.49, p < 0.001], expressive language [β = -1.65; 95% CI -2.46 to -0.84, p < 0.001], and fine motor [β = -0.70; 95% CI -1.20 to -0.20, p = 0.006] scales). There was evidence that child sex interacted with risk and protective factors including birth weight, maternal anaemia in pregnancy, and socioeconomic factors. Important limitations of the study include attrition of sample from birth to assessment age and missing data in some exposure areas from those assessed. CONCLUSIONS: This study provides reliable developmental data from a sub-Saharan African setting in a well-characterised sample of mother-child dyads. Our findings highlight not only the important protective effects of maternal education, birth weight, and socioeconomic status for developmental outcomes but also sex differences in developmental outcomes and key risk and protective factors for each group

Antenatal maternal intimate partner violence exposure is associated with sex-specific alterations in brain structure among young infants: Evidence from a South African birth cohort.

Maternal psychological distress during pregnancy has been linked to adverse outcomes in children with evidence of sex-specific effects on brain development. Here, we investigated whether in utero exposure to intimate partner violence (IPV), a particularly severe maternal stressor, is associated with brain structure in young infants from a South African birth cohort. Exposure to IPV during pregnancy was measured in 143 mothers at 28-32 weeks' gestation and infants underwent structural and diffusion magnetic resonance imaging (mean age 3 weeks). Subcortical volumetric estimates were compared between IPV-exposed (n = 63; 52% female) and unexposed infants (n = 80; 48% female), with white matter microstructure also examined in a subsample (IPV-exposed, n = 28, 54% female; unexposed infants, n = 42, 40% female). In confound adjusted analyses, maternal IPV exposure was associated with sexually dimorphic effects in brain volumes: IPV exposure predicted a larger caudate nucleus among males but not females, and smaller amygdala among females but not males. Diffusivity alterations within white matter tracts of interest were evident in males, but not females exposed to IPV. Results were robust to the removal of mother-infant pairs with pregnancy complications. Further research is required to understand how these early alterations are linked to the sex-bias in neuropsychiatric outcomes later observed in IPV-exposed children

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations

DICER1 and microRNA regulation in post-traumatic stress disorder with comorbid depression

DICER1 is an enzyme that generates mature microRNAs (miRNAs), which regulate gene expression post-transcriptionally in brain and other tissues and is involved in synaptic maturation and plasticity. Here, through genome-wide differential gene expression survey of post-traumatic stress disorder (PTSD) with comorbid depression (PTSD&Dep), we find that blood DICER1 expression is significantly reduced in cases versus controls, and replicate this in two independent cohorts. Our follow-up studies find that lower blood DICER1 expression is significantly associated with increased amygdala activation to fearful stimuli, a neural correlate for PTSD. Additionally, a genetic variant in the 3′ un-translated region of DICER1, rs10144436, is significantly associated with DICER1 expression and with PTSD&Dep, and the latter is replicated in an independent cohort. Furthermore, genome-wide differential expression survey of miRNAs in blood in PTSD&Dep reveals miRNAs to be significantly downregulated in cases versus controls. Together, our novel data suggest DICER1 plays a role in molecular mechanisms of PTSD&Dep through the DICER1 and the miRNA regulation pathway