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1.
Artigo em Inglês | MEDLINE | ID: mdl-33445227

RESUMO

INTRODUCTION: The risk factors for a first episode of psychosis in low and middle-income countries (LMICs) are not well described. The study compared the association of different risk factors in patients with first-episode psychosis patients and healthy controls from an LMIC context. METHODS: A comparative, descriptive, cross-sectional study was performed in antipsychotic naïve first-episode psychosis patients and healthy controls at the National referral hospital in Uganda. Standardized tools were used to assess sociodemographic (e.g., age, sex, socioeconomic status) and clinical (e.g., childhood trauma, quality of life) variables. First episode psychosis participants were compared to healthy controls in terms of sociodemographic and clinical variables, and logistic regression was used to determine predictors of FEP. RESULTS: Our final sample included 198 antipsychotic naïve first-episode psychosis participants and 82 controls. Most participants were female (68.5%) with a mean age of 29.4 years. After adjusting for age and sex, FEP patients when compared to controls were less likely to be female [AOR 0.18 (95%CI 0.03-0.85; p = .031)], more likely to have experienced emotional abuse [AOR 1.30 (95%CI 1.02-1.65; p = .032)] and more likely to have a poor quality of life [AOR 0.93 (95%CI 0.89-0.97; p = .002)]. DISCUSSION: The risk factors for a first episode of psychosis in this low and middle-income population were like those described in high-income countries. Further studies on interventions to prevent the transition to psychotic disorders in this sub-groups of patients are recommended. Also, the use of specialized early intervention services in improving the quality of life needs to be evaluated.

2.
Mol Psychiatry ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33414500

RESUMO

Maternal anxiety during pregnancy is associated with adverse foetal, neonatal, and child outcomes, but biological mechanisms remain unclear. Altered foetal DNA methylation (DNAm) has been proposed as a potential underlying mechanism. In the current study, we performed a meta-analysis to examine the associations between maternal anxiety, measured prospectively during pregnancy, and genome-wide DNAm from umbilical cord blood. Sixteen non-overlapping cohorts from 12 independent longitudinal studies of the Pregnancy And Childhood Epigenetics Consortium participated, resulting in a combined dataset of 7243 mother-child dyads. We examined prenatal anxiety in relation to genome-wide DNAm and differentially methylated regions. We observed no association between the general symptoms of anxiety during pregnancy or pregnancy-related anxiety, and DNAm at any of the CpG sites, after multiple-testing correction. Furthermore, we identify no differentially methylated regions associated with maternal anxiety. At the cohort-level, of the 21 associations observed in individual cohorts, none replicated consistently in the other cohorts. In conclusion, contrary to some previous studies proposing cord blood DNAm as a promising potential mechanism explaining the link between maternal anxiety during pregnancy and adverse outcomes in offspring, we found no consistent evidence for any robust associations between maternal anxiety and DNAm in cord blood. Larger studies and analysis of DNAm in other tissues may be needed to establish subtle or subgroup-specific associations between maternal anxiety and the foetal epigenome.

3.
PLoS One ; 16(1): e0245086, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33428652

RESUMO

BACKGROUND: A high prevalence of metabolic syndrome and its components in patients with psychotic disorders may increase the risk for cardiovascular diseases. Unfortunately, relatively little work in this field has emerged from low-resourced contexts. This study investigated the prevalence, correlates, and treatment patterns of metabolic disorders in patients with psychotic disorders in Western Kenya. METHODS: 300 patients with psychosis and 300 controls were recruited at Moi Teaching and Referral Hospital in Eldoret, Kenya. Data on demographic characteristics, weight, height, abdominal circumference, blood pressure, blood glucose, lipid profile, and treatments were collected. Categorical and continuous data were compared between the patient and control groups using Pearson's chi-squared tests and t-tests, respectively. Variables found to be significantly different between these groups were included in logistic regression models to determine potential predictors of metabolic syndrome. RESULTS: Compared to controls, patients with psychosis were found to have a higher mean random blood glucose [5.23 vs 4.79, p = 0.003], higher body mass index [5.23 vs 4.79, p = 0.001], higher triglycerides [1.98 vs 1.56, p<0.001], larger waist circumference [89.23 vs 86.39, p = 0.009] and lower high density lipoprotein [1.22 vs 1.32, p<0.001]. The odds of developing metabolic syndrome were increased with age [OR = 1.05, CI: 1.02-1.07] and presence of a psychotic disorder [OR = 2.09 [CI 1.23-3.55]; and were reduced with female gender [OR 0.41, CI 0.25-0.67], among those who were never married [OR 0.52, CI 0.28-0.94] and among the widowed/separated/ divorced marital status [OR 0.38, CI 0.17-0.81]. While the majority of patients received treatment with olanzapine, there was no association between olanzapine use and metabolic syndrome and its components. More than half of the patients in this study sample were not receiving treatment for the various components of metabolic syndrome. CONCLUSION: In the study setting of Eldoret, metabolic syndrome and its components were more prevalent among patients with psychotic disorders than in controls; and a clear treatment gap for these disorders was evident. There is a need for efforts to ensure adequate screening and treatment for these physical disorders in resource-limited settings.

4.
Schizophr Res Cogn ; 22: 100187, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32874938

RESUMO

Introduction: Several studies of neuropsychological measures have been undertaken in patients with psychotic disorders from low- and middle-income countries (LMICs). It is, however, unclear if the measures used in these studies are appropriate for cognitive screening in clinical settings. We undertook a systematic review to determine if measures investigated in research on psychotic disorders in LMICs meet the clinical utility criteria proposed by The Working Group on Screening and Assessment. Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses were employed. We determined if tests had been validated against a comprehensive test battery, the duration and scope of the tests, the personnel administering the tests, and the means of administration. Results: A total of 31 articles were included in the review, of which 11 were from Africa. The studies included 3254 participants with psychosis and 1331 controls. 3 studies reported on the validation of the test against a comprehensive cognitive battery. Assessments took 1 h or less to administer in 6/31 studies. The average number of cognitive domains assessed was four. Nonspecialized staff were used in only 3/31 studies, and most studies used pen and paper tests (17/31). Conclusion: Neuropsychological measures used in research on psychotic disorders in LMICs typically do not meet the Working Group on Screening and Assessment clinical utility criteria for cognitive screening. Measures that have been validated in high-income countries but not in LMICs that do meet these criteria, such as the Brief Assessment of Cognition in Schizophrenia, therefore deserve further study in LMIC settings.

5.
Eur Respir J ; 55(3)2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31949118

RESUMO

INTRODUCTION: Indoor air pollution and maternal smoking during pregnancy are associated with respiratory symptoms in infants, but little is known about the direct association with lung function or interactions with genetic risk factors. We examined associations of exposure to indoor particulate matter with a 50% cut-off aerodynamic diameter of 10 µm (PM10) and maternal smoking with infant lung function and the role of gene-environment interactions. METHODS: Data from the Drakenstein Child Health Study, a South African birth cohort, were analysed (n=270). Lung function was measured at 6 weeks and 1 year of age, and lower respiratory tract infection episodes were documented. We measured pre- and postnatal PM10 exposures using devices placed in homes, and prenatal tobacco smoke exposure using maternal urine cotinine levels. Genetic risk scores determined from associations with childhood-onset asthma in the UK Biobank were used to investigate effect modifications. RESULTS: Pre- and postnatal exposure to PM10 as well as maternal smoking during pregnancy were associated with reduced lung function at 6 weeks and 1 year as well as with lower respiratory tract infection in the first year. Due to a significant interaction between the genetic risk score and prenatal exposure to PM10, infants carrying more asthma-related risk alleles were more susceptible to PM10-associated reduced lung function (pinteraction=0.007). This interaction was stronger in infants with Black African ancestry (pinteraction=0.001) and nonexistent in children with mixed ancestry (pinteraction=0.876). CONCLUSIONS: PM10 and maternal smoking exposures were associated with reduced lung function, with a higher susceptibility for infants with an adverse genetic predisposition for asthma that also depended on the infant's ancestry.

6.
Pediatr Pulmonol ; 55(1): 236-244, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31571431

RESUMO

OBJECTIVE: The association of perinatal psychological adversity (ie, stressors and distress) with infant lung function (ILF) and development is not well studied in Africa and elsewhere. We determined the association between maternal perinatal psychological adversity and ILF in African infants. DESIGN: Prospective longitudinal follow up of the Drakenstein Child Health Study birth cohort. PARTICIPANTS: Seven hundred and sixty-two infants aged 6 to 10 weeks and 485 infants who had data for both maternal perinatal psychological adversity and ILF (measured at 6 to 10 weeks and 12 months). METHODS: The main analyses were based on cross-sectional measures of ILF at each assessment (6 to 10 weeks or 12 months), using generalized linear models, and then on the panel-data of both longitudinal ILF assessments, using generalised estimating equations, that allowed specification of the within-group correlation structure. RESULTS: Prenatal intimate partner violence (IPV) exposure was associated with reduced respiratory resistance at 6 to 10 weeks (beta coefficient [ß] = -.131, P = .023); postnatal IPV with reduced ratio of time to peak tidal expiratory flow over total expiratory time (tPTEF /tE ) at 12 months (ß = -.206, P = .016); and prenatal depression with lower respiratory rate at 6 to 10 weeks (ß = -.044, P = .032) and at 12 months (ß = -.053, P = .021). Longitudinal analysis found an association of prenatal IPV with reduced tPTEF /tE (ß = -.052, P < .0001); postnatal IPV with decreased functional residual capacity (FRC; ß = -.086, P < .0001); prenatal posttraumatic stress disorder with increased FRC (ß = .017, P < .0001); prenatal depression with increased FRC (ß = .026, P < .0001) and postnatal depression with increased FRC (ß = .021, P < .0001). CONCLUSION: Screening for psychological adversity and understanding the mechanisms involved may help identify children at risk of altered lung development and inform approaches to treatment.


Assuntos
Grupo com Ancestrais do Continente Africano/psicologia , Depressão , Violência por Parceiro Íntimo , Pulmão/fisiologia , Mães/psicologia , Estresse Psicológico , Adulto , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Gravidez , Testes de Função Respiratória , África do Sul , Adulto Jovem
7.
PLoS One ; 14(11): e0222399, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31751344

RESUMO

BACKGROUND: Maternal physical and mental health during pregnancy are key determinants of birth outcomes. There are relatively few prospective data that integrate physical and mental maternal health measures with birth outcomes in low- and middle-income country settings. We aimed to investigate maternal health during pregnancy and the impact on birth outcomes in an African birth cohort study, the Drakenstein Child Health Study. METHODS: Pregnant women attending 2 public health clinics, Mbekweni (serving a predominantly black African population) and TC Newman (predominantly mixed ancestry) in a poor peri-urban area of South Africa were enrolled in their second trimester and followed through childbirth. All births occurred at a single public hospital. Maternal sociodemographic, physical and psychosocial characteristics were comprehensively assessed. Multivariable linear regression models were used to explore associations between maternal health and birth outcomes. RESULTS: Over 3 years, 1137 women (median age 25.8 years; 21% HIV-infected) gave birth to 1143 live babies. Most pregnancies were uncomplicated but gestational diabetes (1%), anaemia (22%) or pre-eclampsia (2%) occurred in a minority. Most households (87%) had a monthly income of less than USD 350; only 27% of moms were employed and food insecurity was common (37%). Most babies (80%) were born by vaginal delivery at full term; 17% were preterm, predominantly late preterm. Only 74 (7%) of babies required hospitalisation immediately after birth and only 2 babies were HIV-infected. Food insecurity, socioeconomic status, pregnancy-associated hypertension, pre-eclampsia, gestational diabetes and mixed ancestry were associated with lower infant gestational age while maternal BMI at enrolment was associated with higher infant gestational age. Primigravida or alcohol use during pregnancy were negatively associated with infant birth weight and head circumference. Maternal BMI at enrolment was positively associated with birth weight and gestational diabetes was positively associated with birth weight and head circumference for gestational age. Smoking during pregnancy was associated with lower infant birth weight. CONCLUSION: Several modifiable risk factors including food insecurity, smoking, and alcohol consumption during pregnancy were identified as associated with negative birth outcomes, all of which are amenable to public health interventions. Interventions to address key exposures influencing birth outcomes are needed to improve maternal and child health in low-middle income country settings.


Assuntos
Saúde Materna , Resultado da Gravidez , Adulto , Peso ao Nascer , Feminino , Abastecimento de Alimentos , Infecções por HIV/epidemiologia , Cabeça/anatomia & histologia , Cabeça/crescimento & desenvolvimento , Humanos , Recém-Nascido , Estudos Longitudinais , Transtornos Mentais/epidemiologia , Tamanho do Órgão , Gravidez , Complicações na Gravidez/epidemiologia , Estudos Prospectivos , Fatores de Risco , Fatores Socioeconômicos , África do Sul/epidemiologia , Adulto Jovem
8.
Cell ; 179(3): 589-603, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31607513

RESUMO

Genome-wide association studies (GWASs) have focused primarily on populations of European descent, but it is essential that diverse populations become better represented. Increasing diversity among study participants will advance our understanding of genetic architecture in all populations and ensure that genetic research is broadly applicable. To facilitate and promote research in multi-ancestry and admixed cohorts, we outline key methodological considerations and highlight opportunities, challenges, solutions, and areas in need of development. Despite the perception that analyzing genetic data from diverse populations is difficult, it is scientifically and ethically imperative, and there is an expanding analytical toolbox to do it well.


Assuntos
Estudo de Associação Genômica Ampla/métodos , Técnicas de Genotipagem/métodos , Genética Humana/métodos , Confiabilidade dos Dados , Variação Genética , Genética Populacional/métodos , Genética Populacional/normas , Estudo de Associação Genômica Ampla/normas , Técnicas de Genotipagem/normas , Genética Humana/normas , Humanos , Linhagem
9.
PLoS Med ; 16(9): e1002920, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31560687

RESUMO

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 [ß = -0.74; 95% CI -1.46 to -0.03, p = 0.042], receptive language [ß = -1.10; 95% CI -1.70 to -0.49, p < 0.001], expressive language [ß = -1.65; 95% CI -2.46 to -0.84, p < 0.001], and fine motor [ß = -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.


Assuntos
Comportamento Infantil , Desenvolvimento Infantil , Deficiências do Desenvolvimento/epidemiologia , Determinantes Sociais da Saúde , Fatores Socioeconômicos , Fatores Etários , Peso ao Nascer , Pré-Escolar , Deficiências do Desenvolvimento/fisiopatologia , Deficiências do Desenvolvimento/prevenção & controle , Deficiências do Desenvolvimento/psicologia , Escolaridade , Feminino , Humanos , Masculino , Saúde Materna , Fatores de Proteção , Medição de Risco , Fatores de Risco , Fatores Sexuais , África do Sul/epidemiologia
10.
J Affect Disord ; 259: 279-287, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31454590

RESUMO

BACKGROUND: Perinatal depression affects 21-50% of women in South Africa and poses significant health risks to mothers and children. Trajectories of depressive symptoms change over time and have not been well characterized during the perinatal period in low and middle-income countries. METHODS: Data from women enrolled in a population-based birth cohort study in Paarl, South Africa with at least 3 depression measures from pregnancy through 18 months postpartum (N = 831) were analyzed. Depressive symptoms were measured continuously using the Edinburgh Postnatal Depression Scale (EPDS). Group-based trajectory models were used to estimate trajectories of depressive symptoms during the perinatal period and multinomial multivariable models to identify predictors of trajectory group membership. RESULTS: Five distinct trajectory patterns of depressive symptoms were identified: moderate levels of depressive symptoms during pregnancy but minimal postpartum (3.5%), minimal levels during pregnancy and increasing postpartum (3.7%), unstable levels peaking at 12 months postpartum (6.6%), mild levels with slight decrease postpartum (82.9%), and severe levels during pregnancy and postpartum (3.1%). Membership in the chronic severe symptom group was associated with stressful life events, sexual intimate partner violence and tobacco use. LIMITATIONS: Modeling limitations prevented determining how changes in psychosocial predictors over time may influence depressive symptom trajectories. CONCLUSIONS: Mild to severe depressive symptoms during pregnancy/postpartum were common among this South African cohort. Interventions to treat women with severe chronic depressive symptoms with co-occurring psychosocial issues are urgently needed.


Assuntos
Depressão/epidemiologia , Complicações na Gravidez/epidemiologia , Adulto , Depressão/diagnóstico , Depressão/etiologia , Depressão/psicologia , Depressão Pós-Parto/diagnóstico , Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/etiologia , Depressão Pós-Parto/psicologia , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Mães/psicologia , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/etiologia , Complicações na Gravidez/psicologia , Escalas de Graduação Psiquiátrica , Fatores de Risco , Índice de Gravidade de Doença , África do Sul/epidemiologia , Adulto Jovem
11.
Nat Commun ; 10(1): 2548, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31186427

RESUMO

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike's information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.


Assuntos
Metilação de DNA/genética , DNA/sangue , Interação Gene-Ambiente , Estudos de Coortes , Epigênese Genética , Feminino , Sangue Fetal , Genótipo , Humanos , Recém-Nascido , Masculino , Gravidez , Fatores de Risco
12.
Transl Psychiatry ; 9(1): 120, 2019 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-30902966

RESUMO

There have been considerable recent advances in understanding the genetic architecture of Tourette syndrome (TS) as well as its underlying neurocircuitry. However, the mechanisms by which genetic variation that increases risk for TS-and its main symptom dimensions-influence relevant brain regions are poorly understood. Here we undertook a genome-wide investigation of the overlap between TS genetic risk and genetic influences on the volume of specific subcortical brain structures that have been implicated in TS. We obtained summary statistics for the most recent TS genome-wide association study (GWAS) from the TS Psychiatric Genomics Consortium Working Group (4644 cases and 8695 controls) and GWAS of subcortical volumes from the ENIGMA consortium (30,717 individuals). We also undertook analyses using GWAS summary statistics of key symptom factors in TS, namely social disinhibition and symmetry behaviour. SNP effect concordance analysis (SECA) was used to examine genetic pleiotropy-the same SNP affecting two traits-and concordance-the agreement in single nucelotide polymorphism (SNP) effect directions across these two traits. In addition, a conditional false discovery rate (FDR) analysis was performed, conditioning the TS risk variants on each of the seven subcortical and the intracranial brain volume GWAS. Linkage disequilibrium score regression (LDSR) was used as validation of the SECA method. SECA revealed significant pleiotropy between TS and putamen (p = 2 × 10-4) and caudate (p = 4 × 10-4) volumes, independent of direction of effect, and significant concordance between TS and lower thalamic volume (p = 1 × 10-3). LDSR lent additional support for the association between TS and thalamus volume (p = 5.85 × 10-2). Furthermore, SECA revealed significant evidence of concordance between the social disinhibition symptom dimension and lower thalamus volume (p = 1 × 10-3), as well as concordance between symmetry behaviour and greater putamen volume (p = 7 × 10-4). Conditional FDR analysis further revealed novel variants significantly associated with TS (p < 8 × 10-7) when conditioning on intracranial (rs2708146, q = 0.046; and rs72853320, q = 0.035) and hippocampal (rs1922786, q = 0.001) volumes, respectively. These data indicate concordance for genetic variation involved in disorder risk and subcortical brain volumes in TS. Further work with larger samples is needed to fully delineate the genetic architecture of these disorders and their underlying neurocircuitry.


Assuntos
Hipocampo/patologia , Vias Neurais/fisiopatologia , Polimorfismo de Nucleotídeo Único , Putamen/patologia , Síndrome de Tourette/genética , Estudos de Casos e Controles , Análise Mutacional de DNA , Pleiotropia Genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Hipocampo/diagnóstico por imagem , Humanos , Desequilíbrio de Ligação , Imagem por Ressonância Magnética , Putamen/diagnóstico por imagem , Síndrome de Tourette/fisiopatologia
13.
BMJ Open ; 9(3): e018277, 2019 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-30867198

RESUMO

OBJECTIVES: Better understanding of psychosocial risk factors for food insecurity (FI) during pregnancy and how they interact is crucial, given long-term health implications for maternal and child health. We investigated the association between maternal childhood trauma as well as intimate partner violence (IPV) and FI among pregnant women in South Africa, in the Drakenstein Child Health Study, and whether maternal depression mediates these relationships. SETTING: Two primary care clinics in Paarl, South Africa. PARTICIPANTS: 992 pregnant women; inclusion criteria were clinic attendance and remaining in area for at least 1 year; women were excluded if a minor. METHODS: We examined psychosocial predictors of FI using multivariate regression. Mediation analyses investigated whether depression mediated the relationship between IPV and FI as well as between childhood trauma and FI, including disaggregation by two study communities. FI was assessed using an adapted US Department of Agriculture food security scale; households were coded as food insecure where 2 of 5 affirmative responses were recorded. RESULTS: Among 992 pregnant women, there were high rates of IPV (7%-27%), depression (24%) and childhood trauma (34%). In multivariate cross-sectional analysis, emotional IPV (adjusted OR [aOR] 1.60; 95% CI 1.04 to 2.46), depression (aOR 1.05; 95% CI 1.01 to 1.08) and childhood trauma (aOR 1.52; 95% CI 1.08 to 2.15) predicted FI. In mediation models, depression partially mediated the relationship between emotional IPV and FI as well as physical IPV and FI; depression partially mediated the relationship between childhood trauma and FI. Differing degrees of mediation were found when applied to communities. CONCLUSIONS: Antenatal maternal depression, IPV and childhood trauma were highly prevalent and associated with FI. Depression, IPV and trauma screening services should be considered within routine antenatal care and may offer an opportunity to identify and intervene. Community-level differences in risk and in mediation analyses indicate that contextual tailoring of interventions may be important.


Assuntos
Experiências Adversas da Infância/estatística & dados numéricos , Depressão/epidemiologia , Abastecimento de Alimentos/estatística & dados numéricos , Violência por Parceiro Íntimo , Serviços de Saúde Mental/normas , Complicações na Gravidez/epidemiologia , Gestantes/psicologia , Adulto , Feminino , Humanos , Violência por Parceiro Íntimo/psicologia , Violência por Parceiro Íntimo/estatística & dados numéricos , Determinação de Necessidades de Cuidados de Saúde , Gravidez , Prevalência , Psicologia , Fatores de Risco , África do Sul/epidemiologia , Serviços de Saúde da Mulher/normas
14.
J Affect Disord ; 245: 885-896, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30699873

RESUMO

BACKGROUND: There have been considerable recent advances in understanding the genetic architecture of anxiety disorders and posttraumatic stress disorder (PTSD), as well as the underlying neurocircuitry of these disorders. However, there is little work on the concordance of genetic variations that increase risk for these conditions, and that influence subcortical brain structures. We undertook a genome-wide investigation of the overlap between the genetic influences from single nucleotide polymorphisms (SNPs) on volumes of subcortical brain structures and genetic risk for anxiety disorders and PTSD. METHOD: We obtained summary statistics of genome-wide association studies (GWAS) of anxiety disorders (Ncases = 7016, Ncontrols = 14,745), PTSD (European sample; Ncases = 2424, Ncontrols = 7113) and of subcortical brain structures (N = 13,171). SNP Effect Concordance Analysis (SECA) and Linkage Disequilibrium (LD) Score Regression were used to examine genetic pleiotropy, concordance, and genome-wide correlations respectively. SECAs conditional false discovery was used to identify specific risk variants associated with anxiety disorders or PTSD when conditioning on brain related traits. RESULTS: For anxiety disorders, we found evidence of significant concordance between increased anxiety risk variants and variants associated with smaller amygdala volume. Further, by conditioning on brain volume GWAS, we identified novel variants that associate with smaller brain volumes and increase risk for disorders: rs56242606 was found to increase risk for anxiety disorders, while two variants (rs6470292 and rs683250) increase risk for PTSD, when conditioning on the GWAS of putamen volume. LIMITATIONS: Despite using the largest available GWAS summary statistics, the analyses were limited by sample size. CONCLUSIONS: These preliminary data indicate that there is genome wide concordance between genetic risk factors for anxiety disorders and those for smaller amygdala volume, which is consistent with research that supports the involvement of the amygdala in anxiety disorders. It is notable that a genetic variant that contributes to both reduced putamen volume and PTSD plays a key role in the glutamatergic system. Further work with GWAS summary statistics from larger samples, and a more extensive look at the genetics underlying brain circuits, is needed to fully delineate the genetic architecture of these disorders and their underlying neurocircuitry.


Assuntos
Transtornos de Ansiedade/genética , Transtornos de Ansiedade/psicologia , Variação Genética/genética , Vias Neurais/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/genética , Transtornos de Estresse Pós-Traumáticos/psicologia , Tonsila do Cerebelo/diagnóstico por imagem , Transtornos de Ansiedade/fisiopatologia , Encéfalo/diagnóstico por imagem , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Desequilíbrio de Ligação , Masculino , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/fisiopatologia
15.
Child Abuse Negl ; 86: 336-348, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30241702

RESUMO

Intimate partner violence (IPV) is a significant global problem, prevalent in low and middle-income countries (LMICs). IPV is particularly problematic during the perinatal and early postnatal period, where it is linked with negative maternal and child health outcomes. There has been little examination of profiles of IPV and early life adversity in LMIC contexts. We aimed to characterize longitudinal IPV and to investigate maternal maltreatment in childhood as a predictor of IPV exposure during pregnancy and postnatally in a low resource setting. This study was nested in the Drakenstein Child Health Study, a longitudinal birth cohort. Maternal IPV (emotional, physical and sexual) was measured at six timepoints from pregnancy to two years postpartum (n = 832); sociodemographic variables and maternal maltreatment in childhood were measured antenatally at 28-32 weeks' gestation. Associations between maternal maltreatment in childhood and IPV latent class membership (to identify patterns of maternal IPV exposure) were estimated using multinomial and logistic regression. We observed high levels of maternal maltreatment during childhood (34%) and IPV during pregnancy (33%). In latent class analysis separating by IPV sub-type, two latent classes of no/low and moderate sexual IPV and three classes of low, moderate, and high emotional and physical IPV (separately) were detected. In combined latent class analysis, including all IPV sub-types together, a low, moderate and high exposure class emerged as well as a high antenatal/decreasing postnatal class. Moderate and high classes for all IPV sub-types and combined analysis showed stable intensity profiles. Maternal childhood sexual abuse, physical abuse and neglect, and emotional abuse predicted membership in high IPV classes, across all domains of IPV (aORs between 1.99 and 5.86). Maternal maltreatment in childhood was associated with increased probability of experiencing high or moderate intensity IPV during and around pregnancy; emotional neglect was associated with decreasing IPV class for combined model. Intervening early to disrupt this cycle of abuse is critical to two generations.


Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Maus-Tratos Infantis/psicologia , Violência por Parceiro Íntimo/psicologia , Sobreviventes Adultos de Maus-Tratos Infantis/estatística & dados numéricos , Grupo com Ancestrais do Continente Africano/psicologia , Grupo com Ancestrais do Continente Africano/estatística & dados numéricos , Criança , Estudos de Coortes , Exposição à Violência/psicologia , Exposição à Violência/estatística & dados numéricos , Feminino , Humanos , Violência por Parceiro Íntimo/estatística & dados numéricos , Abuso Físico/psicologia , Abuso Físico/estatística & dados numéricos , Gravidez , Prevalência , Estudos Prospectivos , Fatores de Risco , África do Sul/epidemiologia
16.
J Interpers Violence ; : 886260518796522, 2018 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-30160637

RESUMO

Violence against women remains a significant public health problem globally. The majority of longitudinal studies documenting the negative impact of intimate partner violence (IPV) on the mental health of women come from high-income countries. The aim of this study was to investigate the longitudinal association between emotional, physical, or sexual IPV and depression symptoms among South African women in a prospective cohort study. Participants were 981 South African women enrolled in the Drakenstein Child Health Study-a cohort study investigating the early life determinants of child health. Interview data from four time-points (antenatal care visit, 6 months, 12 months, and 18 months postpartum) were included. The primary independent variable was self-reported emotional, physical, and sexual IPV in the past 12 months. Depressive symptoms were assessed at each time-point with the Edinburgh Postnatal Depression Scale (EPDS); a cutoff score of ⩾13 was used to define significant depression symptoms. We used pooled-multivariable logistic regression models to determine associations between the three different forms of IPV and significant depression symptoms while adjusting for time-fixed and time-updated covariates. The mean age of the sample at antenatal care visit was 27 years (standard deviation = 6.0). In the adjusted model including all forms of IPV and adjusting for sociodemographic and clinical characteristics, substance use, and childhood trauma, emotional (adjusted odds ratio [aOR] =1.55, 95% confidence interval (CI): [1.02, 2.34]; p = .039)] and sexual (aOR = 2.02, 95% CI: [1.10, 3.72]; p < .001) IPV were significantly associated with significant depression symptoms. The relationship between physical IPV and significant depression symptoms was not statistically significant (aOR = 0.68, 95% CI: [0.44, 1.05]; p = .485). Our study confirms findings from high-income countries of the association between IPV and depressive symptoms among women in South Africa. Routine screening for IPV, including emotional IPV and intervention programs for IPV among women, is needed in South Africa.

17.
Brain Behav Immun ; 73: 320-330, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29791872

RESUMO

Prenatal exposure to maternal stress and depression has been identified as a risk factor for adverse behavioral and neurodevelopmental outcomes in early childhood. However, the molecular mechanisms through which maternal psychopathology shapes offspring development remain poorly understood. We applied transcriptome-wide screens to 149 umbilical cord blood samples from neonates born to mothers with posttraumatic stress disorder (PTSD; n = 20), depression (n = 31) and PTSD with comorbid depression (n = 13), compared to carefully matched trauma exposed controls (n = 23) and healthy mothers (n = 62). Analyses by maternal diagnoses revealed a clear pattern of gene expression signatures distinguishing neonates born to mothers with a history of psychopathology from those without. Co-expression network analysis identified distinct gene expression perturbations across maternal diagnoses, including two depression-related modules implicated in axon-guidance and mRNA stability, as well as two PTSD-related modules implicated in TNF signaling and cellular response to stress. Notably, these disease-related modules were enriched with brain-expressed genes and genetic risk loci for autism spectrum disorder and schizophrenia, which may imply a causal role for impaired developmental outcomes. These molecular alterations preceded changes in clinical measures at twenty-four months, including reductions in cognitive and socio-emotional outcomes in affected infants. Collectively, these findings indicate that prenatal exposure to maternal psychological distress induces neuronal, immunological and behavioral abnormalities in affected offspring and support the search for early biomarkers of exposures to adverse in utero environments and the classification of children at risk for impaired development.


Assuntos
Transtornos do Neurodesenvolvimento/genética , Efeitos Tardios da Exposição Pré-Natal/genética , Estresse Psicológico/genética , Adulto , Transtorno do Espectro Autista/genética , Cordocentese/métodos , Depressão/fisiopatologia , Depressão/psicologia , Feminino , Sangue Fetal/metabolismo , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mães/psicologia , Transtornos do Neurodesenvolvimento/etiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Fatores de Risco , Esquizofrenia/genética , África do Sul , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Estresse Psicológico/fisiopatologia , Transcriptoma/genética
19.
Alcohol Clin Exp Res ; 42(2): 369-377, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29197115

RESUMO

BACKGROUND: Cohort studies have noted associations between hazardous alcohol use during pregnancy and infant growth outcomes, but many have not controlled for potential psychosocial confounders. To assess the unique contribution of hazardous alcohol use, we examined its effect on infant growth outcomes while controlling for maternal psychosocial stressors and hazardous tobacco and drug use in a cohort of 986 pregnant South African women enrolled into the Drakenstein Child Health Study between 2012 and 2015. METHODS: Data on psychosocial stressors and maternal risk behaviors were collected between 28 and 32 weeks of gestation. Participants were categorized as hazardous alcohol users if they obtained moderate or high scores (>10) on the Alcohol, Smoking and Substance Involvement Screening Test at this assessment or retrospectively reported drinking at least 2 drinks weekly during any trimester of pregnancy. Infant growth outcomes were recorded at delivery. Multivariable regression models examined correlates of hazardous alcohol use and associations between hazardous alcohol use and birth outcomes. RESULTS: Overall, 13% of mothers reported hazardous alcohol use. Recent exposure to intimate partner violence (adjusted odds ratio (aOR) = 2.08; 95% confidence interval (CI): 1.37, 3.18) and hazardous tobacco use (aOR = 5.03; 95% CI: 2.97, 8.52) were significant correlates of hazardous alcohol use. After controlling for potential psychosocial confounders, hazardous alcohol use remained associated with lower infant weight-for-age (B = -0.35, 95% CI: -0.56, -0.14), height-for-age (B = -0.46, 95% CI: -0.76, -0.17), and head-circumference-for-age z-scores (B = -0.43, 95% CI: -0.69, -0.17). CONCLUSIONS: Interventions to reduce hazardous alcohol use among pregnant women in South Africa are needed to prevent alcohol-related infant growth restrictions. As these growth deficits may lead to neurodevelopmental consequences, it is critical to identify alcohol-related growth restrictions at birth and link exposed infants to early interventions for neurodevelopment.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Fumar Cigarros/epidemiologia , Retardo do Crescimento Fetal/epidemiologia , Violência por Parceiro Íntimo/estatística & dados numéricos , Complicações na Gravidez/epidemiologia , Estresse Psicológico/epidemiologia , Adulto , Peso ao Nascer , Estudos de Coortes , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Masculino , Análise Multivariada , Razão de Chances , Gravidez , África do Sul/epidemiologia , Adulto Jovem
20.
Clin Epigenetics ; 9: 75, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28770015

RESUMO

BACKGROUND: 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.


Assuntos
Metilação de DNA , DNA/análise , Sangue Fetal/química , Análise de Sequência de DNA/métodos , Estudos de Coortes , Ilhas de CpG , Contaminação por DNA , Epigênese Genética , Feminino , Humanos , Recém-Nascido , Modelos Lineares , Masculino , Mães , Análise de Sequência com Séries de Oligonucleotídeos/métodos
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