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1.
Brain Res ; 1759: 147386, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33631208

RESUMO

BACKGROUND/OBJECTIVE: The "neural noise" hypothesis suggests that individuals with dyslexia have high glutamate concentrations associated with their reading challenges. Different reading intervention programs have showed low GLX (a combined measure for glutamine and glutamate obtained with in vivo magnetic resonance spectroscopy) in association with reading improvement. Several studies demonstrated improved reading and increased activation in the anterior cingulate cortex following an-executive-function (EF)-based reading intervention. The goals of the current study are two-fold: 1) to determine if the effect of the EF-based reading program extends also to the metabolite concentrations and in particular, on the GLX concentrations in the anterior cingulate cortex; 2) to expand the neural noise hypothesis in dyslexia also to neural networks supporting additional parts of the reading networks, i.e. in specific regions related to executive function skills. METHODS: Children with dyslexia and typical readers were trained on the EF-based reading program. Reading ability was assessed before and after training while spectroscopy data was obtained at the end of the program. The association between change in reading scores following intervention and GLX concentrations was examined. RESULTS: Greater "gains" in word reading were associated with low GLX, Glu, Cr, and NAA concentrations for children with dyslexia compared to typical readers. CONCLUSIONS: These results suggest that the improvement reported following the EF-based reading intervention program also involved a low GLX concentration, as well as additional metabolites previously associated with better reading ability (Glx, Cr, NAA) which may point at the decreased neural noise, especially in the anterior cingulate cortex, as a possible mechanism for the effect of this program.

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.
Health Equity ; 4(1): 489-499, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33269333

RESUMO

Purpose: Maternal stress and psychological dysfunction in pregnancy are independently linked with fetal neurodevelopment. Stress encompasses environmental stressors and psychological and physiological responses. Stressors and psychopathology co-occur with patterns differing by race/ethnicity. We aimed to extend environmental mixtures methodology to elucidate prenatal stress associations with infant negative affectivity (NA) in a racially/ethnically mixed cohort. Methods: Participants were mother/infant dyads (n=445) in a prospective pregnancy cohort study in two urban US settings in 2011-2018. During pregnancy, women completed the Life Stressor Checklist-Revised, Crisis in Family Systems-Revised, Edinburgh Postnatal Depression Scale, and post-traumatic stress disorder (PTSD) Checklist-Civilian version; the Infant Behavior Questionnaire-Revised assessed NA in 6-month olds. Using weighted quantile sum (WQS) regression, we developed a weighted maternal stress index encompassing lifetime and current life events and symptoms of depression and PTSD. Stress-by-race/ethnicity interactions allowed differential contributions of individual stress domains by maternal race/ethnicity. Results: Mothers were majority black (44%) or Hispanic (37%). Stress questionnaire and infant NA scores were similar by race/ethnicity. The WQS prenatal stress score was positively associated with infant NA (ß: 0.40 [95% confidence interval 0.16-0.64]). PTSD was the strongest contributor to the WQS score in Hispanic women (59%), whereas in black women, lifetime stress and depressive symptoms accounted for 38% and 35%, respectively, of the association with NA. Conclusions: Extending environmental mixtures methodology to stress research may disentangle complex associations among lifetime and current stressful life events and psychological symptomatology and their contributions to early childhood neurobehavioral outcomes. Consideration of effect modification by race/ethnicity may inform understanding of differing vulnerability across racial/ethnic groups.

4.
Biol Psychiatry ; 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-33229036

RESUMO

BACKGROUND: Disrupted placental functioning due to stress can have lifelong implications. Cumulative stress and trauma are likely to have lasting impacts on maternal physiological functioning and offspring development, resulting in increased risk for later-life complex disorders for which racial disparities exist. METHODS: This study examined the association between maternal lifetime stress and placental mitochondrial DNA mutational load in an urban multiethnic cohort. Maternal lifetime exposure to stressful events was assessed using the validated Life Stressor Checklist-Revised. Whole mitochondrial DNA sequencing was performed and mutations were determined for 365 placenta samples with complete exposure and covariate data. Multivariable regression was used to model maternal lifetime stress in relation to placental mitochondrial DNA mutational load. Racial/ethnic differences were examined by cross-product terms and contrast statements. Gene-wise analyses were conducted. RESULTS: We identified 13,189 heteroplasmies (Phred score > 10,000, minor allele frequency < 0.5, number of mutant reads > 1). Women experiencing increased psychosocial stress over their lifetime exhibited a higher number of total placental mitochondrial mutations (ß = .23, 95% confidence interval = .03 to .42) and heteroplasmic mutations (ß = .18, 95% confidence interval = .05 to .31) but not homoplasmic mutations (ß = -.008, 95% confidence interval = -.03 to .01); the strongest associations were observed among Black women and genes coding for NADH dehydrogenase and cytochrome c oxidase subunits. CONCLUSIONS: Cumulative maternal lifetime stress is associated with a greater mitochondrial mutational load, particularly among Black women. The impact of racial/ethnic differences in mutational load on placental function directly affecting offspring development and/or leading to chronic disease disparities warrants further investigation.

5.
Environ Health Perspect ; 127(10): 107007, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31663780

RESUMO

BACKGROUND: The autonomic nervous system plays a key role in maintaining homeostasis and responding to external stimuli. In adults, exposure to fine particulate matter (PM2.5) has been associated with reduced heart rate variability (HRV), an indicator of cardiac autonomic control. OBJECTIVES: Our goal was to investigate the associations of exposure to fine particulate matter (PM2.5) with HRV as an indicator of cardiac autonomic control during early development. METHODS: We studied 237 maternal-infant pairs in a Boston-based birth cohort. We estimated daily residential PM2.5 using satellite data in combination with land-use regression predictors. In infants at 6 months of age, we measured parasympathetic nervous system (PNS) activity using continuous electrocardiogram monitoring during the Repeated Still-Face Paradigm, an experimental protocol designed to elicit autonomic reactivity in response to maternal interaction and disengagement. We used multivariable linear regression to examine average PM2.5 exposure across pregnancy in relation to PNS withdrawal and activation, indexed by changes in respiration-corrected respiratory sinus arrhythmia (RSAc)-an established metric of HRV that reflects cardiac vagal tone. We examined interactions with infant sex using cross-product terms. RESULTS: In adjusted models we found that a 1-unit increase in PM2.5 (in micrograms per cubic meter) was associated with a 3.53% decrease in baseline RSAc (95% CI: -6.96, 0.02). In models examining RSAc change between episodes, higher PM2.5 was generally associated with reduced PNS withdrawal during stress and reduced PNS activation during recovery; however, these associations were not statistically significant. We did not observe a significant interaction between PM2.5 and sex. DISCUSSION: Prenatal exposure to PM2.5 may disrupt cardiac vagal tone during infancy. Future research is needed to replicate these preliminary findings. https://doi.org/10.1289/EHP4434.


Assuntos
Poluentes Atmosféricos/toxicidade , Sistema Nervoso Autônomo/efeitos dos fármacos , Coração/efeitos dos fármacos , Exposição Materna/estatística & dados numéricos , Material Particulado/toxicidade , Adulto , Poluentes Atmosféricos/análise , Boston , Feminino , Humanos , Lactente , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal
6.
Environ Res ; 175: 71-78, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31103795

RESUMO

BACKGROUND: Exposure to traffic-related air pollution (TRAP) has been linked to childhood anxiety symptoms. Neuroimaging in patients with anxiety disorders indicate altered neurochemistry. OBJECTIVES: Evaluate the impact of TRAP on brain metabolism and its relation to childhood anxiety symptoms in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS). METHODS: Adolescents (n = 145) underwent magnetic resonance spectroscopy. Brain metabolites, including myo-inositol, N-acetylaspartate, creatine, choline, glutamate, glutamate plus glutamine, and glutathione were measured in the anterior cingulate cortex. Anxiety symptoms were assessed using the Spence Children's Anxiety Scale. TRAP exposure in early-life, averaged over childhood, and during the 12 months prior to imaging was estimated using a validated land use regression model. Associations between TRAP exposure, brain metabolism, and anxiety symptoms were estimated using linear regression and a bootstrapping approach for testing mediation by brain metabolite levels. RESULTS: Recent exposure to high levels of TRAP was associated with significant increases in myo-inositol (ß = 0.26; 95%CI 0.01, 0.51) compared to low TRAP exposure. Recent elevated TRAP exposure (ß = 4.71; 95% CI 0.95, 8.45) and increased myo-inositol levels (ß = 2.98; 95% CI 0.43, 5.52) were also significantly associated with increased generalized anxiety symptoms with 12% of the total effect between TRAP and generalized anxiety symptoms being mediated by myo-inositol levels. CONCLUSIONS: This is the first study of children to utilize neuroimaging to link TRAP exposure, metabolite dysregulation in the brain, and generalized anxiety symptoms among otherwise healthy children. TRAP may elicit atypical excitatory neurotransmission and glial inflammatory responses leading to increased metabolite levels and subsequent anxiety symptoms.


Assuntos
Ansiedade , Encéfalo , Inositol , Poluição Relacionada com o Tráfego , Adolescente , Ansiedade/etiologia , Encéfalo/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Inositol/análise , Espectroscopia de Ressonância Magnética , Masculino , Poluição Relacionada com o Tráfego/efeitos adversos
7.
Front Hum Neurosci ; 12: 466, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30532701

RESUMO

Children with dyslexia exhibit slow and inaccurate reading, as well as problems in executive functions. Decreased signal activation in brain regions related to visual processing and executive functions has been observed with functional magnetic resonance imaging with reports of sex differences in brain patterns for visual processing regions. However, the underlying neurochemistry associated with deficits in executive functions for children with dyslexia has not been thoroughly evaluated. Reading ability and executive functions were assessed in fifty-three children [ages 8-12 years old, dyslexia (n = 24), and typical readers (n = 30)]. We employed short echo, single voxel, proton magnetic resonance spectroscopy to evaluate the perigenual anterior cingulate cortex (ACC). Pearson correlations were calculated between metabolite concentrations and measures of reading, processing speed, and executive function. Logistic regression models were used to determine the effects of brain metabolite concentrations, processing speed, and reading scores on dyslexia status. Differences by child's sex were also examined. Compared to typical readers, higher global executive composite t-score is associated with greater odds for dyslexia (OR 1.14; 95% CI 1.05, 1.23); increased processing speed appears to be protective for dyslexia (OR 0.95; 95% 0.89-1.00). After adjustment for multiple comparisons, females with dyslexia showed strong and significant negative correlations between processing speed and myo-inositol (r = -0.55, p = 0.005) and choline (r = -0.54, p = 0.005) concentrations; effect modification by sex was confirmed in linear regression models (psex∗Cho = 0.0006) and (psex∗mI = 0.01). These associations were not observed for males or the group as a whole. These findings suggest that children with dyslexia share difficulty in one or more areas of executive function, specifically those related to response time. Also, metabolite changes in the ACC may be present in children with dyslexia, especially for females, and may hold value as possible markers for dyslexia.

8.
J Pediatr ; 203: 301-308, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30197200

RESUMO

OBJECTIVES: To evaluate associations between maternal lifetime traumatic stress and offspring birthweight and examine modifying effects of third trimester cortisol and fetal sex. STUDY DESIGN: Analyses included 314 mother-infant dyads from an ethnically mixed pregnancy cohort. Maternal lifetime trauma was reported via the Life Stressor Checklist-Revised. Fenton birthweight for gestational age z-scores (BWGA-z) were calculated. A 3-cm scalp-nearest maternal hair segment collected at birth was assayed to reflect cumulative third trimester cortisol secretion. Multivariable regression was used to investigate associations between maternal lifetime trauma and BWGA-z and examine 2- and 3-way interactions with cortisol and fetal sex. Because subjects with low or high cortisol levels could represent susceptible populations, varying coefficient models that relax the linearity assumption on cortisol level were used to assess the modification of maternal lifetime trauma associations with BWGA-z as a function of cortisol. RESULTS: Women were primarily minorities (41% Hispanic, 26% black) with ≤12 years education (63%); 63% reported ≥1 traumatic event. Prenatal cortisol modified the association between maternal lifetime trauma and birthweight. Women with higher lifetime trauma and increased cortisol had significantly lower birthweight infants in males; among males exposed to the 90th percentile of cortisol, a 1-unit increase in trauma score was associated with a 0.19-unit decrease in BWGA-z (95% CI, -0.34 to -0.04). Associations among females were nonsignificant, regardless of cortisol level. CONCLUSIONS: These findings underscore the need to consider complex interactions among maternal trauma, disrupted in utero cortisol production, and fetal sex to fully elucidate intergenerational effects of maternal lifetime trauma.


Assuntos
Cabelo/química , Hidrocortisona/análise , Mães , Estresse Psicológico/fisiopatologia , Adulto , Peso ao Nascer , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Feminino , Idade Gestacional , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Masculino , Análise Multivariada , Gravidez , Fatores Sexuais
9.
Epigenetics ; 13(6): 665-681, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30001177

RESUMO

Evolving evidence links maternal stress exposure to changes in placental DNA methylation of specific genes regulating placental function that may have implications for the programming of a host of chronic disorders. Few studies have implemented an epigenome-wide approach. Using the Infinium HumanMethylation450 BeadChip (450K), we investigated epigenome-wide placental DNA methylation in relation to maternal experiences of traumatic and non-traumatic stressors over her lifetime assessed using the Life Stressor Checklist-Revised (LSC-R) survey (n = 207). We found differential DNA methylation at epigenome-wide statistical significance (FDR = 0.05) for 112 CpGs. Additionally, we observed three clusters that exhibited differential methylation in response to high maternal lifetime stress. Enrichment analyses, conducted at an FDR = 0.20, revealed lysine degradation to be the most significant pathway associated with maternal lifetimes stress exposure. Targeted enrichment analyses of the three largest clusters of probes, identified using the gap statistic, were enriched for genes associated with endocytosis (i.e., SMAP1, ANKFY1), tight junctions (i.e., EPB41L4B), and metabolic pathways (i.e., INPP5E, EEF1B2). These pathways, also identified in the top 10 KEGG pathways associated with maternal lifetime stress exposure, play important roles in multiple physiological functions necessary for proper fetal development. Further, two genes were identified to exhibit multiple probes associated with maternal lifetime stress (i.e., ANKFY1, TM6SF1). The methylation status of the probes belonging to each cluster and/or genes exhibiting multiple hits, may play a role in the pathogenesis of adverse health outcomes in children born to mothers with increased lifetime stress exposure.


Assuntos
Metilação de DNA , Epigênese Genética , Placenta/metabolismo , Estresse Psicológico/genética , Adulto , Feminino , Genoma Humano , Humanos , Gravidez
10.
Respir Res ; 19(1): 76, 2018 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-29703190

RESUMO

BACKGROUND: In utero exposure to particulate matter with an aerodynamic diameter of less than 2.5 µm (PM2.5) has been linked to child lung function. Overlapping evidence suggests that child sex and exposure timing may modify effects and associations may be mediated through glutathione S-transferase P1 (GSTP1) methylation. METHODS: We prospectively examined associations among prenatal PM2.5 exposure and child lung function and GSTP1 methylation in an urban pregnancy cohort study. We employed a validated satellite-based spatiotemporally resolved prediction model to estimate daily prenatal PM2.5 exposure over gestation. We used Baysian distributed lag interaction models (BDLIMs) to identify sensitive windows for prenatal PM2.5 exposure on child lung function and nasal epithelia GSTP1 methylation at age 7 years, and to examine effect modification by child sex. RESULTS: BDLIMs identified a sensitive window for prenatal PM2.5 exposure at 35-40 weeks gestation [cumulative effect estimate (CEE) = - 0.10, 95%CI = - 0.19 to - 0.01, per µg/m3 increase in PM2.5] and at 36-40 weeks (CEE = - 0.12, 95%CI = - 0.20 to - 0.01) on FEV1 and FVC, respectively, in boys. BDLIMs also identified a sensitive window of exposure at 37-40 weeks gestation between higher prenatal PM2.5 exposure and increased GSTP1 percent methylation. The association between higher GSTP1 percent methylation and decreased FEV1 was borderline significant in the sample as a whole (ß = - 0.37, SE = 0.20, p = 0.06) and in boys in stratified analyses (ß = - 0.56, SE = 0.29, p = 0.05). CONCLUSIONS: Prenatal PM2.5 exposure in late pregnancy was associated with impaired early childhood lung function and hypermethylation of GSTPI in DNA isolated from nasal epithelial cells. There was a trend towards higher GSTP1 percent methylation being associated with reduced FEV1. All findings were most evident among boys.


Assuntos
Metilação de DNA/fisiologia , Glutationa S-Transferase pi/metabolismo , Mucosa Nasal/metabolismo , Material Particulado/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Caracteres Sexuais , Adulto , Poluentes Atmosféricos/efeitos adversos , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Tamanho da Partícula , Gravidez , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Estudos Prospectivos
12.
Environ Int ; 112: 49-58, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29248865

RESUMO

BACKGROUND: Prenatal ambient fine particulate matter (PM2.5) and maternal chronic psychosocial stress have independently been linked to changes in mithochondrial DNA copy number (mtDNAcn), a marker of mitochondrial response and dysfunction. Further, overlapping research shows sex-specific effects of PM2.5 and stress on developmental outcomes. Interactions among PM2.5, maternal stress, and child sex have not been examined in this context. METHODS: We examined associations among exposure to prenatal PM2.5, maternal lifetime traumatic stressors, and mtDNAcn at birth in a sociodemographically diverse pregnancy cohort (N=167). Mothers' daily exposure to PM2.5 over gestation was estimated using a satellite-based spatio-temporally resolved prediction model. Lifetime exposure to traumatic stressors was ascertained using the Life Stressor Checklist-Revised; exposure was categorized as high vs. low based on a median split. Quantitative real-time polymerase chain reaction (qPCR) was used to determine mtDNAcn in placenta and cord blood leukocytes. Bayesian Distributed Lag Interaction regression models (BDLIMs) were used to statistically model and visualize the PM2.5 timing-dependent pattern of associations with mtDNAcn and explore effect modification by maternal lifetime trauma and child sex. RESULTS: Increased PM2.5 exposure across pregnancy was associated with decreased mtDNAcn in cord blood (cumulative effect estimate=-0.78; 95%CI -1.41, -0.16). Higher maternal lifetime trauma was associated with reduced mtDNAcn in placenta (ß=-0.33; 95%CI -0.63, -0.02). Among women reporting low trauma, increased PM2.5 exposure late in pregnancy (30-38weeks gestation) was significantly associated with decreased mtDNAcn in placenta; no significant association was found in the high trauma group. BDLIMs identified a significant 3-way interaction between PM2.5, maternal trauma, and child sex. Specifically, PM2.5 exposure between 25 and 40weeks gestation was significantly associated with increased placental mtDNAcn among boys of mothers reporting high trauma. In contrast, PM2.5 exposure in this same window was significantly associated with decreased placental mtDNAcn among girls of mothers reporting low trauma. Similar 3-way interactive effects were observed in cord blood. CONCLUSIONS: These results indicate that joint exposure to PM2.5 in late pregnancy and maternal lifetime trauma influence mtDNAcn at the maternal-fetal interface in a sex-specific manner. Additional studies will assist in understanding if the sex-specific patterns reflect distinct pathophysiological processes in addition to mitochondrial dysfunction.


Assuntos
DNA Mitocondrial/efeitos dos fármacos , Exposição Materna/estatística & dados numéricos , Material Particulado/toxicidade , Variações do Número de Cópias de DNA/efeitos dos fármacos , Feminino , Humanos , Masculino , Gravidez
13.
Infancy ; 22(4): 492-513, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28983193

RESUMO

Little research has examined the impact of maternal lifetime trauma exposure on infant temperament. We examined associations between maternal trauma history and infant negative affectivity and modification by prenatal cortisol exposure in a sociodemographically diverse sample of mother-infant dyads. During pregnancy, mothers completed measures of lifetime trauma exposure and current stressors. Third-trimester cortisol output was assessed from maternal hair. When infants were 6 months old, mothers completed the Infant Behavior Questionnaire-Revised. In analyses that controlled for infant sex and maternal age, education, race/ethnicity, and stress during pregnancy, greater maternal trauma exposure was associated with increased infant distress to limitations and sadness. Higher and lower prenatal cortisol exposure modified the magnitude and direction of association between maternal trauma history and infant rate of recovery from arousal. The association between maternal trauma history and infant distress to limitations was somewhat stronger among infants exposed to higher levels of prenatal cortisol. The analyses suggested that maternal lifetime trauma exposure is associated with several domains of infant negative affectivity independently of maternal stress exposures during pregnancy and that some of these associations may be modified by prenatal cortisol exposure. The findings have implications for understanding the intergenerational impact of trauma exposure on child developmental outcomes.

14.
Am J Epidemiol ; 186(11): 1227-1236, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28595325

RESUMO

Psychosocial stress contributes to placental oxidative stress. Mitochondria are vulnerable to oxidative stress, which can lead to changes in mitochondrial DNA copy number (mtDNAcn). We examined associations of maternal lifetime stress, current negative life events, and depressive and posttraumatic-stress-disorder symptom scores with placental mtDNAcn in a racially/ethnically diverse sample (n = 147) from the Programming of Intergenerational Stress Mechanisms (PRISM) study (Massachusetts, March 2011 to August 2012). In linear regression analyses adjusted for maternal age, race/ethnicity, education, prenatal fine particulate matter exposure, prenatal smoking exposure, and the sex of the child, all measures of stress were associated with decreased placental mtDNAcn (all P values < 0.05). Weighted-quantile-sum (WQS) regression showed that higher lifetime stress and depressive symptoms accounted for most of the effect on mtDNAcn (WQS weights: 0.25 and 0.39, respectively). However, among white individuals, increased lifetime stress and posttraumatic stress disorder symptoms explained the majority of the effect (WQS weights: 0.20 and 0.62, respectively) while among nonwhite individuals, lifetime stress and depressive symptoms accounted for most of the effect (WQS weights: 0.27 and 0.55, respectively). These analyses are first to link increased maternal psychosocial stress with reduced placental mtDNAcn and add to literature documenting racial/ethnic differences in the psychological sequelae of chronic stress that may contribute to maternal-fetal health.


Assuntos
Variações do Número de Cópias de DNA , DNA Mitocondrial/sangue , Depressão/fisiopatologia , Estresse Oxidativo/fisiologia , Placenta , Complicações na Gravidez/psicologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Estresse Psicológico/fisiopatologia , Afro-Americanos/psicologia , Afro-Americanos/estatística & dados numéricos , Biomarcadores/sangue , DNA Mitocondrial/genética , Depressão/genética , Escolaridade , Grupo com Ancestrais do Continente Europeu/psicologia , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Feminino , Hispano-Americanos/psicologia , Hispano-Americanos/estatística & dados numéricos , Humanos , Recém-Nascido , Modelos Lineares , Masculino , Massachusetts/epidemiologia , Estresse Oxidativo/genética , Gravidez , Complicações na Gravidez/etnologia , Complicações na Gravidez/etiologia , Complicações na Gravidez/genética , Estudos Prospectivos , Transtornos de Estresse Pós-Traumáticos/genética , Estresse Psicológico/genética
15.
Epigenomics ; 9(3): 231-240, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28234020

RESUMO

AIM: We compared predictive modeling approaches to estimate placental methylation using cord blood methylation. MATERIALS & METHODS: We performed locus-specific methylation prediction using both linear regression and support vector machine models with 174 matched pairs of 450k arrays. RESULTS: At most CpG sites, both approaches gave poor predictions in spite of a misleading improvement in array-wide correlation. CpG islands and gene promoters, but not enhancers, were the genomic contexts where the correlation between measured and predicted placental methylation levels achieved higher values. We provide a list of 714 sites where both models achieved an R2 ≥0.75. CONCLUSION: The present study indicates the need for caution in interpreting cross-tissue predictions. Few methylation sites can be predicted between cord blood and placenta.


Assuntos
Metilação de DNA , Epigênese Genética , Sangue Fetal/metabolismo , Genoma Humano , Modelos Genéticos , Placenta/metabolismo , Ilhas de CpG , Elementos Facilitadores Genéticos , Feminino , Humanos , Gravidez , Regiões Promotoras Genéticas , Máquina de Vetores de Suporte
16.
Psychosom Med ; 79(1): 91-100, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27359172

RESUMO

OBJECTIVE: Traumatic stressors, including child abuse and/or interpersonal violence over a woman's lifecourse, can affect the health of her children. This study examines the associations between maternal lifetime interpersonal trauma (IPT) and children's asthma by age 6 years (n = 857). METHODS: Pregnant women completed the Revised Conflict Tactics Scale; IPT exposure was categorized as unexposed (55%), early (childhood and/or teen years only, 25%), late (adulthood and/or index pregnancy, 7%), and chronic (early and late, 13%). Clinician-diagnosed asthma in children was reported by mothers at each follow-up visit until the child reached age 6 years. We examined the effects of maternal IPT categories and child's asthma using logistic regression. Using structural equation models, we also examined indirect relationships between maternal chronic IPT and child asthma operating through active asthma in pregnancy, prepregnancy BMI, prenatal smoking, and/or increased exposure to other adverse life events or environmental toxins prenatally. Effect modification by the child's sex was examined. RESULTS: Mothers were primarily Hispanic (55%) or black (30%) with less than high school education (62%). In logistic regression models, chronic maternal IPT (compared with unexposed) was associated with asthma in boys (odds ratio = 2.87, 95% confidence interval = 1.48-5.57) but not girls (odds ratio = 0.69, 95% confidence interval = 0.23-2.12; pinteraction = .042). In structural equation models, chronic IPT was associated with maternal active asthma in pregnancy (ß = 0.59, p < .001), maternal active asthma was associated with children's asthma (ß = 0.20, p = .009), and the total indirect effect for this path was significant (ß = 0.12, p = .031). Associations were most evident among boys. CONCLUSIONS: Mothers' history of chronic IPT was associated with asthma in boys. This association was mediated through active maternal asthma in pregnancy.


Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis/estatística & dados numéricos , Asma/epidemiologia , Exposição à Violência/estatística & dados numéricos , Complicações na Gravidez/epidemiologia , Adulto , Afro-Americanos/estatística & dados numéricos , Boston/epidemiologia , Criança , Feminino , Hispano-Americanos/estatística & dados numéricos , Humanos , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fatores Sexuais , Adulto Jovem
17.
Matern Child Health J ; 20(2): 250-60, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26511128

RESUMO

OBJECTIVE(S): To validate the Block98 food frequency questionnaire (FFQ) for estimating antioxidant, methyl-nutrient and polyunsaturated fatty acids (PUFA) intakes in a pregnant sample of ethnic/racial minority women in the United States (US). METHODS: Participants (n = 42) were from the Programming of Intergenerational Stress Mechanisms study. Total micronutrient intakes from food and supplements was ascertained using the modified Block98 FFQ and two 24-h dietary recalls collected at random on nonconsecutive days subsequent to completion of the FFQ in mid-pregnancy. Correlation coefficients (r) corrected for attenuation from within-person variation in the recalls were calculated for antioxidants (n = 7), methyl-nutrients (n = 8), and PUFAs (n = 2). RESULT(S): The sample was largely ethnic minorities (38 % Black, 33 % Hispanic) with 21 % being foreign born and 41 % having less than or equal to a high school degree. Significant and adequate deattenuated correlations (r ≥ 0.40) for total dietary intakes of antioxidants were observed for vitamin C, vitamin E, magnesium, and zinc. Reasonable deattenuated correlations were also observed for methyl-nutrient intakes of vitamin B6, betaine, iron, and n:6 PUFAs; however, they did not reach significance. Most women were classified into the same or adjacent quartiles (≥70 %) for total (dietary + supplements) estimates of antioxidants (5 out of 7) and methyl-nutrients (4 out of 5). CONCLUSIONS: The Block98 FFQ is an appropriate dietary method for evaluating antioxidants in pregnant ethnic/minorities in the US; it may be less efficient in measuring methyl-nutrient and PUFA intakes.


Assuntos
Inquéritos sobre Dietas/normas , Dieta/estatística & dados numéricos , Micronutrientes/administração & dosagem , Avaliação Nutricional , Gestantes/etnologia , Inquéritos e Questionários/normas , Adulto , Antioxidantes/administração & dosagem , Registros de Dieta , Suplementos Nutricionais , Ácidos Graxos Insaturados/administração & dosagem , Feminino , Humanos , Rememoração Mental , Gravidez , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estados Unidos , População Urbana , Adulto Jovem
18.
J Appl Toxicol ; 35(9): 976-91, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26046650

RESUMO

The amount of scientific research linking environmental exposures and childhood health outcomes continues to grow; yet few studies have teased out the mechanisms involved in environmentally-induced diseases. Cells can respond to environmental stressors in many ways: inducing oxidative stress/inflammation, changes in energy production and epigenetic alterations. Mitochondria, tiny organelles that each retains their own DNA, are exquisitely sensitive to environmental insults and are thought to be central players in these pathways. While it is intuitive that mitochondria play an important role in disease processes, given that every cell of our body is dependent on energy metabolism, it is less clear how environmental exposures impact mitochondrial mechanisms that may lead to enhanced risk of disease. Many of the effects of the environment are initiated in utero and integrating mitochondriomics into children's environmental health studies is a critical priority. This review will highlight (i) the importance of exploring environmental mitochondriomics in children's environmental health, (ii) why environmental mitochondriomics is well suited to biomarker development in this context, and (iii) how molecular and epigenetic changes in mitochondria and mitochondrial DNA (mtDNA) may reflect exposures linked to childhood health outcomes.


Assuntos
Exposição Ambiental , Saúde Ambiental/métodos , Poluentes Ambientais/toxicidade , Mitocôndrias/efeitos dos fármacos , Asma/induzido quimicamente , Asma/genética , Criança , Dano ao DNA , DNA Mitocondrial/efeitos dos fármacos , DNA Mitocondrial/genética , Epigênese Genética , Interação Gene-Ambiente , Humanos , Mitocôndrias/genética , Doenças Neurodegenerativas/induzido quimicamente , Doenças Neurodegenerativas/genética , Fatores de Risco
19.
Am J Respir Crit Care Med ; 192(4): 421-7, 2015 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-26106807

RESUMO

RATIONALE: The timing and duration of traffic-related air pollution (TRAP) exposure may be important for childhood wheezing and asthma development. OBJECTIVES: We examined the relationship between TRAP exposure and longitudinal wheezing phenotypes and asthma at age 7 years. METHODS: Children completed clinical examinations annually from age 1 year through age 4 years and age 7 years. Parental-reported wheezing was assessed at each age, and longitudinal wheezing phenotypes (early-transient, late-onset, persistent) and asthma were defined at age 7 years. Participants' time-weighted exposure to TRAP, from birth through age 7 years, was estimated using a land-use regression model. The relationship between TRAP exposure and wheezing phenotypes and asthma was examined. MEASUREMENTS AND MAIN RESULTS: High TRAP exposure at birth was significantly associated with both transient and persistent wheezing phenotypes (adjusted odds ratio [aOR] = 1.64; 95% confidence interval [CI], 1.04-2.57 and aOR = 2.31; 95% CI, 1.28-4.15, respectively); exposure from birth to age 1 year and age 1 to 2 years was also associated with persistent wheeze. Only children with high average TRAP exposure from birth through age 7 years were at significantly increased risk for asthma (aOR = 1.71; 95% CI, 1.01-2.88). CONCLUSIONS: Early-life exposure to TRAP is associated with increased risk for persistent wheezing, but only long-term exposure to high levels of TRAP throughout childhood was associated with asthma development.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Asma/epidemiologia , Exposição Ambiental/efeitos adversos , Sons Respiratórios/etiologia , Emissões de Veículos , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Fatores de Risco , Fatores de Tempo
20.
Artigo em Inglês | MEDLINE | ID: mdl-25328835

RESUMO

BACKGROUND: Infant temperament predicts a range of developmental and behavioral outcomes throughout childhood. Both maternal fatty acid intake and psychosocial stress exposures during pregnancy may influence infant temperament. Furthermore, maternal race may modify prenatal diet and stress effects. The goals of this study are to examine the joint effects of prenatal diet and stress and the modifying effects of race on infant behavior. METHODS: Analyses included N=255 mother-infant dyads, primarily minorities (21% Blacks; 42% Hispanics), enrolled in an urban pregnancy cohort. Maternal prenatal stress was indexed by a negative life events (NLEs) score on the Crisis in Family Systems-Revised survey. Prenatal total daily intakes of polyunsaturated fatty acids (PUFAs) (n3, n6) were estimated from a food frequency questionnaire; n3:n6 ratios were calculated. Mothers completed the Infant Behavior Questionnaire-Revised (IBQ-R), a measure of infant temperament, when the children were 6 months old. Three commonly used dimensions were derived: Orienting & Regulation, Extraversion, and Negative Affectivity. Associations among prenatal stress, maternal n3:n6 ratio, and race/ethnicity on infant temperament, controlling for maternal education and age and child sex, were examined. RESULTS: Among Blacks, prenatal stress effects on infant Orienting & Regulation scores were modified by maternal n3:n6 ratios (p=0.03): As NLEs increased, lower n3:n6 ratios predicted lower infant Orienting & Regulation scores, whereas higher n3:n6 ratios attenuated the effect of prenatal stress. There were no main or interaction effects predicting Extraversion or Negative Affectivity. CONCLUSIONS: An optimal PUFA ratio may protect the fetus from stress effects on infant behavior, particularly among Blacks. These findings may have implications for later neurodevelopment and social functioning predicted by early temperamental characteristics.

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