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1.
Mol Autism ; 10: 36, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31673306

RESUMO

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects more than 1% of children in the USA. ASD risk is thought to arise from both genetic and environmental factors, with the perinatal period as a critical window. Understanding early transcriptional changes in ASD would assist in clarifying disease pathogenesis and identifying biomarkers. However, little is known about umbilical cord blood gene expression profiles in babies later diagnosed with ASD compared to non-typically developing and non-ASD (Non-TD) or typically developing (TD) children. Methods: Genome-wide transcript levels were measured by Affymetrix Human Gene 2.0 array in RNA from cord blood samples from both the Markers of Autism Risk in Babies-Learning Early Signs (MARBLES) and the Early Autism Risk Longitudinal Investigation (EARLI) high-risk pregnancy cohorts that enroll younger siblings of a child previously diagnosed with ASD. Younger siblings were diagnosed based on assessments at 36 months, and 59 ASD, 92 Non-TD, and 120 TD subjects were included. Using both differential expression analysis and weighted gene correlation network analysis, gene expression between ASD and TD, and between Non-TD and TD, was compared within each study and via meta-analysis. Results: While cord blood gene expression differences comparing either ASD or Non-TD to TD did not reach genome-wide significance, 172 genes were nominally differentially expressed between ASD and TD cord blood (log2(fold change) > 0.1, p < 0.01). These genes were significantly enriched for functions in xenobiotic metabolism, chromatin regulation, and systemic lupus erythematosus (FDR q < 0.05). In contrast, 66 genes were nominally differentially expressed between Non-TD and TD, including 8 genes that were also differentially expressed in ASD. Gene coexpression modules were significantly correlated with demographic factors and cell type proportions. Limitations: ASD-associated gene expression differences identified in this study are subtle, as cord blood is not the main affected tissue, it is composed of many cell types, and ASD is a heterogeneous disorder. Conclusions: This is the first study to identify gene expression differences in cord blood specific to ASD through a meta-analysis across two prospective pregnancy cohorts. The enriched gene pathways support involvement of environmental, immune, and epigenetic mechanisms in ASD etiology.

2.
Environ Health Perspect ; 127(5): 57012, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31148503

RESUMO

BACKGROUND: Prenatal exposure to air pollution has been associated with childhood respiratory disease and other adverse outcomes. Epigenetics is a suggested link between exposures and health outcomes. OBJECTIVES: We aimed to investigate associations between prenatal exposure to particulate matter (PM) with diameter [Formula: see text] ([Formula: see text]) or [Formula: see text] ([Formula: see text]) and DNA methylation in newborns and children. METHODS: We meta-analyzed associations between exposure to [Formula: see text] ([Formula: see text]) and [Formula: see text] ([Formula: see text]) at maternal home addresses during pregnancy and newborn DNA methylation assessed by Illumina Infinium HumanMethylation450K BeadChip in nine European and American studies, with replication in 688 independent newborns and look-up analyses in 2,118 older children. We used two approaches, one focusing on single cytosine-phosphate-guanine (CpG) sites and another on differentially methylated regions (DMRs). We also related PM exposures to blood mRNA expression. RESULTS: Six CpGs were significantly associated [false discovery rate (FDR) [Formula: see text]] with prenatal [Formula: see text] and 14 with [Formula: see text] exposure. Two of the [Formula: see text] CpGs mapped to FAM13A (cg00905156) and NOTCH4 (cg06849931) previously associated with lung function and asthma. Although these associations did not replicate in the smaller newborn sample, both CpGs were significant ([Formula: see text]) in 7- to 9-y-olds. For cg06849931, however, the direction of the association was inconsistent. Concurrent [Formula: see text] exposure was associated with a significantly higher NOTCH4 expression at age 16 y. We also identified several DMRs associated with either prenatal [Formula: see text] and or [Formula: see text] exposure, of which two [Formula: see text] DMRs, including H19 and MARCH11, replicated in newborns. CONCLUSIONS: Several differentially methylated CpGs and DMRs associated with prenatal PM exposure were identified in newborns, with annotation to genes previously implicated in lung-related outcomes. https://doi.org/10.1289/EHP4522.

3.
Environ Int ; 126: 363-376, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30826615

RESUMO

BACKGROUND: Prenatal air pollution exposure has been linked to many adverse health conditions in the offspring. However, little is known about the mechanisms underlying these associations. Epigenetics may be one plausible biologic link. Here, we sought to identify site-specific and global DNA methylation (DNAm) changes, in developmentally relevant tissues, associated with prenatal exposure to nitrogen dioxide (NO2) and ozone (O3). Additionally, we assessed whether sex-specific changes in methylation exist and whether DNAm changes are consistently observed across tissues. METHODS: Genome-scale DNAm measurements were obtained using the Infinium HumanMethylation450k platform for 133 placenta and 175 cord blood specimens from Early Autism Risk Longitudinal Investigation (EARLI) neonates. Ambient NO2 and O3 exposure levels were based on prenatal address locations of EARLI mothers and the Environmental Protection Agency's AirNOW monitoring network using inverse distance weighting. We computed sample-level aggregate methylation measures for each of 5 types of genomic regions including genome-wide, open sea, shelf, shore, and island regions. Linear regression was performed for each genomic region; per-sample aggregate methylation measures were modeled as a function of quantitative exposure level with covariate adjustment. In addition, bumphunting was performed to identify differentially methylated regions (DMRs) associated with prenatal O3 and NO2 exposures in each tissue and by sex, with adjustment for technical and biological sources of variation. RESULTS: We identified global and locus-specific changes in DNA methylation related to prenatal exposure to NO2 and O3 in 2 developmentally relevant tissues. Neonates with increased prenatal O3 exposure had lower aggregate levels of DNAm at CpGs located in open sea and shelf regions of the genome. We identified 6 DMRs associated with prenatal NO2 exposure, including 3 sex-specific. An additional 3 sex-specific DMRs were associated with prenatal O3 exposure levels. DMRs initially detected in cord blood samples (n = 4) showed consistent exposure-related changes in DNAm in placenta. However, the DMRs initially detected in placenta (n = 5) did not show DNAm differences in cord blood and, thus, they appear to be tissue-specific. CONCLUSIONS: We observed global, locus, and sex-specific methylation changes associated with prenatal NO2 and O3 exposures. Our findings support DNAm is a biologic target of prenatal air pollutant exposures and highlight epigenetic involvement in sex-specific differential susceptibility to environmental exposure effects in 2 developmentally relevant tissues.


Assuntos
Poluição do Ar/análise , Metilação de DNA , Troca Materno-Fetal , Poluentes Atmosféricos/análise , Saúde da Criança , Epigenômica , Feminino , Humanos , Saúde do Lactente , Recém-Nascido , Masculino , Exposição Materna , Dióxido de Nitrogênio/análise , Ozônio/análise , Placenta/química , Gravidez
4.
Environ Health Perspect ; 126(3): 037004, 2018 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-29553459

RESUMO

BACKGROUND: Previous studies have reported associations of perinatal exposure to air toxics, including some metals and volatile organic compounds, with autism spectrum disorder (ASD). OBJECTIVES: Our goal was to further explore associations of perinatal air toxics with ASD and associated quantitative traits in high-risk multiplex families. METHODS: We included participants of a U.S. family-based study [the Autism Genetic Resource Exchange (AGRE)] who were born between 1994 and 2007 and had address information. We assessed associations between average annual concentrations at birth for each of 155 air toxics from the U.S. EPA emissions-based National-scale Air Toxics Assessment and a) ASD diagnosis (1,540 cases and 477 controls); b) a continuous measure of autism-related traits, the Social Responsiveness Scale (SRS, among 1,272 cases and controls); and c) a measure of autism severity, the Calibrated Severity Score (among 1,380 cases). In addition to the individual's air toxic level, mixed models (clustering on family) included the family mean air toxic level, birth year, and census covariates, with consideration of the false discovery rate. RESULTS: ASD diagnosis was positively associated with propionaldehyde, methyl tert-butyl ether (MTBE), bromoform, 1,4-dioxane, dibenzofurans, and glycol ethers and was inversely associated with 1,4-dichlorobenzene, 4,4'-methylene diphenyl diisocyanate (MDI), benzidine, and ethyl carbamate (urethane). These associations were robust to adjustment in two-pollutant models. Autism severity was associated positively with carbon disulfide and chlorobenzene, and negatively with 1,4-dichlorobenzene. There were no associations with the SRS. CONCLUSIONS: Some air toxics were associated with ASD risk and severity, including some traffic-related air pollutants and newly-reported associations, but other previously reported associations with metals and volatile organic compounds were not reproducible. https://doi.org/10.1289/EHP1867.

5.
Artigo em Inglês | MEDLINE | ID: mdl-29561551

RESUMO

Polycyclic aromatic hydrocarbons (PAH) are ubiquitous air pollutants associated with negative impacts on growth, development and behavior in children. Source-specific biological markers of PAH exposure are needed for targeting interventions to protect children. Nitro-derivatives of PAH can act as markers of exposure to diesel exhaust, gasoline exhaust, or general combustion sources. Using a novel HPLC-APCI-MS/MS detection method, we examined four hemoglobin (Hb) adducts of nitro-PAH metabolites and the Hb adduct of a benzo[a]pyrene (BaP) metabolite in 22 umbilical cord blood samples. The samples were collected from a birth cohort with comprehensive data on prenatal PAH exposure, including prenatal personal air monitoring and DNA adducts in maternal and umbilical cord blood. Using non-parametric analyses, heat maps, and principal component analysis (PCA), we analyzed the relationship between the five Hb adducts and previous PAH measurements, with each measurement representing a different duration of exposure. We found that Hb adducts derived from several diesel-related nitro-PAHs (2-nitrofluorene and 1-nitropyrene) were significantly correlated (r = 0.77, p ≤ 0.0001) and grouped together in PCA. Nitro-PAH derived Hb adducts were largely unrelated to previously collected measures of exposure to a number of PAH parent compounds. These measures need to be validated in a larger sample.

6.
Autism Res ; 11(1): 69-80, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29120534

RESUMO

Independent studies report that periconceptional folic acid (FA) may decrease the risk of autism spectrum disorder (ASD) while exposure to air pollution may increase ASD risk. We examined the joint effects of gestational FA and air pollution exposures in association with ASD. We studied 346 ASD cases and 260 typically developing controls from the CHARGE case-control study. Self-reported FA intake for each month of pregnancy was quantified. Estimates of exposure to near roadway air pollution (NRP) and criteria air pollutant measures were assigned based on maternal residential history. Among mothers with high FA intake (>800 µg) in the first pregnancy month, exposure to increasing levels of all air pollutants, except ozone, during the first trimester was associated with decreased ASD risk, while increased ASD risk was observed for the same pollutant among mothers with low FA intake (≤800 µg). This difference was statistically significant for NO2 (e.g., NO2 and low FA intake: OR = 1.53 (0.91, 2.56) vs NO2 and high FA intake: OR = 0.74 (0.46, 1.19), P-interaction = 0.04). Mothers exposed to higher levels (≥ median) of any air pollutant during the first trimester of pregnancy and who reported low FA intake were at a higher ASD risk compared to mothers exposed to lower levels of that air pollutant and who reported high first month FA intake. Joint effects showed significant (alpha < 0.10) departures from expected interaction for NRP and NO2 . Our results suggest that periconceptional FA intake may reduce ASD risk in those with high prenatal air pollution exposure. Further study is needed to replicate these findings in larger sample sizes and to understand mechanisms of this potential relationship.. Autism Res 2018, 11: 69-80. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We examined interactions between periconceptional folic acid (FA) and air pollution exposure on risk of ASD. Mothers exposed to higher levels of air pollution during the first trimester of pregnancy and who reported low supplemental FA intake during the first pregnancy month were at a higher ASD risk compared to mothers exposed to lower levels of air pollution and who reported high first month FA intake. Our results suggest that periconceptional FA intake may reduce ASD risk in those with high prenatal air pollution exposure.

7.
Environ Health Perspect ; 125(9): 097007, 2017 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-28934093

RESUMO

BACKGROUND: Maternal folic acid (FA) protects against developmental toxicity from certain environmental chemicals. OBJECTIVE: We examined combined exposures to maternal FA and pesticides in relation to autism spectrum disorder (ASD). METHODS: Participants were California children born from 2000-2007 who were enrolled in the Childhood Autism Risks from Genetics and the Environment (CHARGE) case-control study at age 2-5 y, were clinically confirmed to have ASD (n=296) or typical development (n=220), and had information on maternal supplemental FA and pesticide exposures. Maternal supplemental FA and household pesticide product use were retrospectively collected in telephone interviews from 2003-2011. High vs. low daily FA intake was dichotomized at 800µg (median). Mothers' addresses were linked to a statewide database of commercial applications to estimate agricultural pesticide exposure. RESULTS: High FA intake (≥800µg) during the first pregnancy month and no known pesticide exposure was the reference group for all analyses. Compared with this group, ASD was increased in association with <800µg FA and any indoor pesticide exposure {adjusted odds ratio [OR]=2.5 [95% confidence interval (CI): 1.3, 4.7]} compared with low FA [OR=1.2 (95% CI: 0.7, 2.2)] or indoor pesticides [OR=1.7 (95% CI: 1.1, 2.8)] alone. ORs for the combination of low FA and regular pregnancy exposure (≥6 mo) to pet pesticides or to outdoor sprays and foggers were 3.9 (95% CI: 1.4, 11.5) and 4.1 (95% CI: 1.7, 10.1), respectively. ORs for low maternal FA and agricultural pesticide exposure 3 mo before or after conception were 2.2 (95% CI: 0.7, 6.5) for chlorpyrifos, 2.3 (95% CI: 0.98, 5.3) for organophosphates, 2.1 (95% CI: 0.9, 4.8) for pyrethroids, and 1.5 (95% CI: 0.5, 4.8) for carbamates. Except for carbamates, these ORs were approximately two times greater than those for either exposure alone or for the expected ORs for combined exposures under multiplicative or additive models. CONCLUSIONS: In this study population, associations between pesticide exposures and ASD were attenuated among those with high versus low FA intake during the first month of pregnancy. Confirmatory and mechanistic studies are needed. https://doi.org/10.1289/EHP604.


Assuntos
Transtorno do Espectro Autista/epidemiologia , Suplementos Nutricionais , Poluentes Ambientais/metabolismo , Ácido Fólico/uso terapêutico , Exposição Materna/estatística & dados numéricos , Praguicidas/metabolismo , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Adulto , California/epidemiologia , Estudos de Casos e Controles , Criança , Transtornos Globais do Desenvolvimento Infantil/epidemiologia , Feminino , Humanos , Masculino , Gravidez
8.
Environ Health Perspect ; 124(1): 133-40, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26068947

RESUMO

BACKGROUND: Prenatal exposure to air pollutants has been suggested as a possible etiologic factor for the occurrence of autism spectrum disorder. OBJECTIVES: We aimed to assess whether prenatal air pollution exposure is associated with childhood autistic traits in the general population. METHODS: Ours was a collaborative study of four European population-based birth/child cohorts-CATSS (Sweden), Generation R (the Netherlands), GASPII (Italy), and INMA (Spain). Nitrogen oxides (NO2, NOx) and particulate matter (PM) with diameters of ≤ 2.5 µm (PM2.5), ≤ 10 µm (PM10), and between 2.5 and 10 µm (PM(coarse)), and PM2.5 absorbance were estimated for birth addresses by land-use regression models based on monitoring campaigns performed between 2008 and 2011. Levels were extrapolated back in time to exact pregnancy periods. We quantitatively assessed autistic traits when the child was between 4 and 10 years of age. Children were classified with autistic traits within the borderline/clinical range and within the clinical range using validated cut-offs. Adjusted cohort-specific effect estimates were combined using random-effects meta-analysis. RESULTS: A total of 8,079 children were included. Prenatal air pollution exposure was not associated with autistic traits within the borderline/clinical range (odds ratio = 0.94; 95% CI: 0.81, 1.10 per each 10-µg/m3 increase in NO2 pregnancy levels). Similar results were observed in the different cohorts, for the other pollutants, and in assessments of children with autistic traits within the clinical range or children with autistic traits as a quantitative score. CONCLUSIONS: Prenatal exposure to NO2 and PM was not associated with autistic traits in children from 4 to 10 years of age in four European population-based birth/child cohort studies. CITATION: Guxens M, Ghassabian A, Gong T, Garcia-Esteban R, Porta D, Giorgis-Allemand L, Almqvist C, Aranbarri A, Beelen R, Badaloni C, Cesaroni G, de Nazelle A, Estarlich M, Forastiere F, Forns J, Gehring U, Ibarluzea J, Jaddoe VW, Korek M, Lichtenstein P, Nieuwenhuijsen MJ, Rebagliato M, Slama R, Tiemeier H, Verhulst FC, Volk HE, Pershagen G, Brunekreef B, Sunyer J. 2016. Air pollution exposure during pregnancy and childhood autistic traits in four European population-based cohort studies: the ESCAPE Project. Environ Health Perspect 124:133-140; http://dx.doi.org/10.1289/ehp.1408483.


Assuntos
Poluição do Ar/efeitos adversos , Transtorno Autístico/epidemiologia , Material Particulado/toxicidade , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Óxidos de Nitrogênio/metabolismo , Gravidez
9.
Early Hum Dev ; 91(8): 483-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26073892

RESUMO

BACKGROUND: Vitamin D is essential for proper neurodevelopment and cognitive and behavioral function. We examined associations between autism spectrum disorder (ASD) and common, functional polymorphisms in vitamin D pathways. METHODS: Children aged 24-60 months enrolled from 2003 to 2009 in the population-based CHARGE case-control study were evaluated clinically and confirmed to have ASD (n=474) or typical development (TD, n=281). Maternal, paternal, and child DNA samples for 384 (81%) families of children with ASD and 234 (83%) families of TD children were genotyped for: TaqI, BsmI, FokI, and Cdx2 in the vitamin D receptor (VDR) gene, and CYP27B1 rs4646536, GC rs4588, and CYP2R1 rs10741657. Case-control logistic regression, family-based log-linear, and hybrid log-linear analyses were conducted to produce risk estimates and 95% confidence intervals (CI) for each allelic variant. RESULTS: Paternal VDR TaqI homozygous variant genotype was significantly associated with ASD in case-control analysis (odds ratio [OR] [CI]: 6.3 [1.9-20.7]) and there was a trend towards increased risk associated with VDR BsmI (OR [CI]: 4.7 [1.6-13.4]). Log-linear triad analyses detected parental imprinting, with greater effects of paternally-derived VDR alleles. Child GC AA-genotype/A-allele was associated with ASD in log-linear and ETDT analyses. A significant association between decreased ASD risk and child CYP2R1 AA-genotype was found in hybrid log-linear analysis. There were limitations of low statistical power for less common alleles due to missing paternal genotypes. CONCLUSIONS: This study provides preliminary evidence that paternal and child vitamin D metabolism could play a role in the etiology of ASD; further research in larger study populations is warranted.


Assuntos
Transtorno do Espectro Autista/genética , Colestanotriol 26-Mono-Oxigenase/genética , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , Adulto , Estudos de Casos e Controles , Pré-Escolar , Família 2 do Citocromo P450 , Pai , Feminino , Humanos , Masculino , Vitamina D/sangue
10.
J Pers Assess ; 97(5): 506-14, 2015 Sep-Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25893676

RESUMO

Anhedonia-the reduced capacity to experience pleasure-is a trait implicated in mental and physical health. Yet, psychometric data on anhedonia measures in adolescents are absent. We conducted an in-depth psychometric analysis of the Snaith-Hamilton Pleasure Scale (SHAPS; Snaith et al., 1995 )-a self-report measure of anticipated pleasure response to 14 pleasant experiences-in adolescents. Adolescents (N = 585, M age = 14.5) completed the SHAPS and other paper-and-pencil surveys. Item response theory models were used to evaluate the psychometric performance of each SHAPS item. Correlations of the SHAPS with other personality and psychopathology measures were calculated to evaluate construct validity. Results showed that (a) certain items (e.g., reported pleasure from basic experiences like "seeing smiling faces" or "smelling flowers") provided more information about latent anhedonia than others; and (b) SHAPS scales exhibited construct-consistent convergent and discriminant validity (i.e., stronger correlations with low positive affect constructs, weaker correlations with negative affect). Reporting diminished pleasure from basic pleasant experiences accurately indicates adolescent anhedonia, which is important for future scale development and understanding the phenomenology of anhedonia in teens. These data support using the SHAPS for assessing anhedonia in epidemiological research and school-based universal prevention programming in general adolescent populations.


Assuntos
Comportamento do Adolescente/fisiologia , Anedonia/fisiologia , Escalas de Graduação Psiquiátrica/normas , Psicometria/instrumentação , Adolescente , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes
11.
Epidemiology ; 25(1): 44-7, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24240654

RESUMO

BACKGROUND: Independent studies report association of autism spectrum disorder with air pollution exposure and a functional promoter variant (rs1858830) in the MET receptor tyrosine kinase (MET) gene. Toxicological data find altered brain Met expression in mice after prenatal exposure to a model air pollutant. Our objective was to investigate whether air pollution exposure and MET rs1858830 genotype interact to alter the risk of autism spectrum disorder. METHODS: We studied 252 cases of autism spectrum disorder and 156 typically developing controls from the Childhood Autism Risk from Genetics and the Environment Study. Air pollution exposure was assigned for local traffic-related sources and regional sources (particulate matter, nitrogen dioxide, and ozone). MET genotype was determined by direct resequencing. RESULTS: Subjects with both MET rs1858830 CC genotype and high air pollutant exposures were at increased risk of autism spectrum disorder compared with subjects who had both the CG/GG genotypes and lower air pollutant exposures. There was evidence of multiplicative interaction between NO2 and MET CC genotype (P= 0.03). CONCLUSIONS: MET rs1858830 CC genotype and air pollutant exposure may interact to increase the risk of autism spectrum disorder.


Assuntos
Poluição do Ar/estatística & dados numéricos , Transtornos Globais do Desenvolvimento Infantil/genética , Interação Gene-Ambiente , Proteínas Proto-Oncogênicas c-met/genética , Estudos de Casos e Controles , Transtornos Globais do Desenvolvimento Infantil/epidemiologia , Pré-Escolar , Exposição Ambiental , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Modelos Logísticos , Masculino , Dióxido de Nitrogênio , Ozônio , Material Particulado , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Emissões de Veículos
12.
JAMA Psychiatry ; 70(1): 71-7, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23404082

RESUMO

CONTEXT: Autism is a heterogeneous disorder with genetic and environmental factors likely contributing to its origins. Examination of hazardous pollutants has suggested the importance of air toxics in the etiology of autism, yet little research has examined its association with local levels of air pollution using residence-specific exposure assignments. OBJECTIVE: To examine the relationship between traffic-related air pollution, air quality, and autism. DESIGN: This population-based case-control study includes data obtained from children with autism and control children with typical development who were enrolled in the Childhood Autism Risks from Genetics and the Environment study in California. The mother's address from the birth certificate and addresses reported from a residential history questionnaire were used to estimate exposure for each trimester of pregnancy and first year of life. Traffic-related air pollution was assigned to each location using a line-source air-quality dispersion model. Regional air pollutant measures were based on the Environmental Protection Agency's Air Quality System data. Logistic regression models compared estimated and measured pollutant levels for children with autism and for control children with typical development. SETTING: Case-control study from California. PARTICIPANTS: A total of 279 children with autism and a total of 245 control children with typical development. MAIN OUTCOME MEASURES: Crude and multivariable adjusted odds ratios (AORs) for autism. RESULTS: Children with autism were more likely to live at residences that had the highest quartile of exposure to traffic-related air pollution, during gestation (AOR, 1.98 [95% CI, 1.20-3.31]) and during the first year of life (AOR, 3.10 [95% CI, 1.76-5.57]), compared with control children. Regional exposure measures of nitrogen dioxide and particulate matter less than 2.5 and 10 µm in diameter (PM2.5 and PM10) were also associated with autism during gestation (exposure to nitrogen dioxide: AOR, 1.81 [95% CI, 1.37-3.09]; exposure to PM2.5: AOR, 2.08 [95% CI, 1.93-2.25]; exposure to PM10: AOR, 2.17 [95% CI, 1.49-3.16) and during the first year of life (exposure to nitrogen dioxide: AOR, 2.06 [95% CI, 1.37-3.09]; exposure to PM2.5: AOR, 2.12 [95% CI, 1.45-3.10]; exposure to PM10: AOR, 2.14 [95% CI, 1.46-3.12]). All regional pollutant estimates were scaled to twice the standard deviation of the distribution for all pregnancy estimates. CONCLUSIONS: Exposure to traffic-related air pollution, nitrogen dioxide, PM2.5, and PM10 during pregnancy and during the first year of life was associated with autism. Further epidemiological and toxicological examinations of likely biological pathways will help determine whether these associations are causal.


Assuntos
Poluição do Ar/efeitos adversos , Transtorno Autístico/etiologia , Material Particulado/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Transtorno Autístico/epidemiologia , California/epidemiologia , Estudos de Casos e Controles , Pré-Escolar , Monitoramento Ambiental , Feminino , Humanos , Lactente , Masculino , Dióxido de Nitrogênio/efeitos adversos , Gravidez , Inquéritos e Questionários
13.
Environ Health Perspect ; 119(6): 873-7, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21156395

RESUMO

BACKGROUND: Little is known about environmental causes and contributing factors for autism. Basic science and epidemiologic research suggest that oxidative stress and inflammation may play a role in disease development. Traffic-related air pollution, a common exposure with established effects on these pathways, contains substances found to have adverse prenatal effects. OBJECTIVES: We examined the association between autism and proximity of residence to freeways and major roadways during pregnancy and near the time of delivery, as a surrogate for air pollution exposure. METHODS: Data were from 304 autism cases and 259 typically developing controls enrolled in the Childhood Autism Risks from Genetics and the Environment (CHARGE) study. The mother's address recorded on the birth certificate and trimester-specific addresses derived from a residential history obtained by questionnaire were geocoded, and measures of distance to freeways and major roads were calculated using ArcGIS software. Logistic regression models compared residential proximity to freeways and major roads for autism cases and typically developing controls. RESULTS: Adjusting for sociodemographic factors and maternal smoking, maternal residence at the time of delivery was more likely be near a freeway (≤ 309 m) for cases than for controls [odds ratio (OR)=1.86; 95% confidence interval (CI), 1.04-3.45]. Autism was also associated with residential proximity to a freeway during the third trimester (OR=2.22; CI, 1.16-4.42). After adjustment for socioeconomic and sociodemographic characteristics, these associations were unchanged. Living near other major roads at birth was not associated with autism. CONCLUSIONS: Living near a freeway was associated with autism. Examination of associations with measured air pollutants is needed.


Assuntos
Poluentes Atmosféricos/toxicidade , Transtorno Autístico/epidemiologia , Exposição Ambiental , Emissões de Veículos/toxicidade , Poluentes Atmosféricos/análise , Transtorno Autístico/induzido quimicamente , California/epidemiologia , Estudos de Casos e Controles , Pré-Escolar , Feminino , Sistemas de Informação Geográfica , Humanos , Modelos Logísticos , Masculino , Razão de Chances , Gravidez , Características de Residência , Saúde da População Urbana , Emissões de Veículos/análise
14.
J Am Acad Child Adolesc Psychiatry ; 48(4): 441-50, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19318883

RESUMO

OBJECTIVE: New attention-deficit/hyperactivity disorder (ADHD) subtypes identified through latent class analysis have been recently proposed. Here, we assess the accuracy of simple rules based on symptom counts for the assignment of youths to clinically relevant population-derived ADHD subtypes: severe inattentive (SI) and severe combined (SC). METHOD: Data from 9,675 twins and siblings from Missouri and Australia aged 7 to 19 years were analyzed using continuous and categorical models of ADHD symptoms using principal components analysis and subtyping by DSM-IV and by latent class criteria. Cut points were derived for classifying SI and SC subtypes by positive predictive value, negative predictive value, percent positive agreement, and Matthew coefficient of agreement. RESULTS: Principal components analysis suggested two underlying factors: total number of symptoms and symptom type, with SI and SC latent class subtypes clearly mapping to distinct areas on a plot of these factors. Having six or more total symptoms and fewer than three hyperactive-impulsive symptoms accurately predicts the latent class SI subtype. The latent class SC subtype was best identified by 11 or more total symptoms and 4 or more hyperactive-impulsive. The DSM-IV ADHD subtype criteria accurately identified the SC subtype but only poorly for the SI subtype. CONCLUSIONS: Symptom counts criteria allow the simple and accurate identification of subjects with severe ADHD subtypes defined by latent class analysis. Such simple symptom counts corresponding to screening cut points selected latent class-derived SI subtype subjects with greater precision than DSM-IV criteria.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/classificação , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Adolescente , Criança , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , Adulto Jovem
15.
J Child Psychol Psychiatry ; 48(5): 464-72, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17501727

RESUMO

BACKGROUND: Most diagnostic nomenclatures do not allow for the concurrent diagnosis of autism and attention-deficit/hyperactivity disorder (ADHD). Clinic-based studies suggest autistic symptoms are common in children with ADHD, but such studies are prone to referral bias. This study assesses whether children with ADHD selected from the general twin population have elevated levels of autistic traits. METHODS: Nine hundred forty-six twins identified by Missouri birth records were assigned to DSM-IV ADHD diagnoses and seven population-derived ADHD subtypes defined through latent class analysis of DSM-IV ADHD symptoms. The Social Responsiveness Scale (SRS) was used as a quantitative measure of autistic traits. Linear regression was used to evaluate whether mean SRS scores differed between ADHD diagnostic groups. RESULTS: Mean SRS scores for DSM-IV predominantly inattentive subtype and combined subtype ADHD groups were significantly higher than for subjects without DSM-IV ADHD (p < .001, both comparisons). Five of the population-derived ADHD subtypes (talkative-impulsive, mild and severe inattentive, mild and severe combined) had significantly higher mean SRS scores compared to the latent class subtype with few ADHD symptoms (p < .001, all comparisons). DSM-IV combined subtype and the population-derived severe combined subtype had the highest mean total SRS scores and the highest mean scores for each of the three autism symptom domains, with a substantial proportion of individuals scoring in the clinically significant range. CONCLUSIONS: This study provides population-based evidence for clinically significant elevations of autistic traits in children meeting diagnostic criteria for ADHD. These results have implications for the design and interpretation of studies of both disorders.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno Autístico/diagnóstico , Adolescente , Adulto , Criança , Comportamento Infantil , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Missouri , Gêmeos
16.
Biol Psychiatry ; 62(2): 115-20, 2007 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-16950211

RESUMO

BACKGROUND: A profile of Child Behavior Checklist(CBCL) T-scores>or=70 on the attention problems, aggression, and anxious/depressed subscales has been proposed to identify juvenile bipolar disorder(JBD). We tested this hypothesis in a population-based sample. METHODS: Data for this analysis come from a birth-records-based twin sample having semi-structured interview and CBCL data (N=1,346). We compared prevalence of DSM-IV psychiatric disorders and suicidal behaviors in CBCL-JBD and non-CBCL-JBD subjects. Twin modeling assessed genetic and environmental contributions to CBCL-JBD. Associations with DRD4 and DAT1 were examined using chi-square tests. RESULTS: The prevalence of CBCL-JBD was 2.5%. No subjects with CBCL-JBD met criteria for bipolar or other mood disorders. CBCL-JBD subjects had more oppositional defiant disorder (ODD), conduct disorder(CD), and attention deficit hyperactivity disorder(ADHD). The CBCL-JBD profile was uncommon in these disorders. CBCL-JBD subjects more frequently endorsed suicidal behaviors. The CBCL-JBD profile was heritable and associated with the number of DAT1 9-repeat 3' untranslated region alleles. CONCLUSIONS: The CBCL-JBD phenotype does not correspond with a semi-structured interview assessment of JBD. ADHD, CD, and ODD are common in children with CBCL-JBD but do not account for the profile. Increased suicidal behaviors indicate substantial impairment in CBCL-JBD subjects.


Assuntos
Transtorno Bipolar/diagnóstico , Transtorno Bipolar/genética , Inventário de Personalidade/estatística & dados numéricos , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno Bipolar/epidemiologia , Criança , Estudos de Coortes , Comorbidade , Manual Diagnóstico e Estatístico de Transtornos Mentais , Doenças em Gêmeos/diagnóstico , Doenças em Gêmeos/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Feminino , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Modelos Genéticos , Determinação da Personalidade , Fenótipo , Escalas de Graduação Psiquiátrica , Psicologia do Adolescente , Psicometria , Receptores de Dopamina D4/genética
17.
Drug Alcohol Depend ; 87(2-3): 225-32, 2007 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-16987611

RESUMO

Alcohol dependence (AD) and nicotine dependence (ND) have been shown to co-occur. Results from twin studies implicate the role of genetics in the etiology of both ND and AD with substantial, yet incomplete, overlap. To test for specificity of transmission of AD and ND in an offspring of twins sample we analyzed data from a study of adolescent and adult offspring of twin fathers ascertained from the Vietnam Era Twin Registry. This sample consists of 1213 twin fathers, 862 biologic or rearing mothers, and 1270 offspring. Offspring were allocated to one of four risk groups for AD based on twin fathers' zygosity and father's and cotwins AD history. Offspring DSM-IV AD and ND were measured by structured diagnostic interview. Paternal AD and ND were significantly associated with offspring AD and ND, respectively. Bivariate probit regression results suggest specificity for transmission of AD and ND. This remained constant after controlling for offspring demographics and psychopathology and maternal AD and ND. Despite the substantial genetic overlap between the two disorders, there is evidence for genetic effects specific for AD and ND.


Assuntos
Alcoolismo/epidemiologia , Tabagismo/epidemiologia , Adolescente , Adulto , Criança , Comorbidade , Características da Família , Feminino , Humanos , Entrevistas como Assunto , Masculino , Relações Pais-Filho , Sistema de Registros , Fatores de Risco , Estados Unidos
18.
Twin Res Hum Genet ; 9(5): 623-31, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17032541

RESUMO

Long-term memory (LTM) problems are associated with many psychiatric and neurological illnesses and are commonly measured using free and cued recall tasks. Although LTM has been linked with biologic mechanisms, the etiology of distinct LTM tasks is unknown. We studied LTM in 95 healthy female twin pairs identified through birth records in the state of Missouri. Performance on tasks of free recall of unrelated words, free and cued recall of categorized words, and the vocabulary section of the Wechsler Adult Intelligence Scale (WAIS-R) were examined using structural equation modeling. Additive genetic and unique environmental factors influenced LTM and intelligence. Free recall of unrelated and categorized words, and cued recall of categorized words, were moderately heritable (55%, 38%, and 37%). WAIS-R vocabulary score was highly heritable (77%). Controlling for verbal intelligence in multivariate analyses of recall, two components of genetic influence on LTM were found; one for all three recall scores and one for free and cued categorized word recall. Recall of unrelated and categorized words is influenced by different genetic and environmental factors indicating heterogeneity in LTM. Verbal intelligence is etiologically different from LTM indicating that these two abilities utilize different brain functions.


Assuntos
Genética Comportamental , Rememoração Mental , Adulto , Sinais (Psicologia) , Feminino , Humanos , Testes de Inteligência , Estudos Prospectivos , Análise e Desempenho de Tarefas
19.
Am J Med Genet B Neuropsychiatr Genet ; 141B(3): 312-8, 2006 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-16526027

RESUMO

Statistically based classification methods have successfully refined ADHD into homogenous and heritable subtypes. External validity and impairment of these subtypes was examined using the Child Behavior Checklist (CBCL). We compared mean CBCL syndrome and competency t-scores across ADHD subtypes defined by latent class analysis in a sample of 1,346 individual twins from Missouri. The potential for comorbidity with conduct disorder (CD), oppositional defiant disorder (ODD), or major depression (MD) to increase impairment in specific ADHD subtypes was also examined. CBCL profiles confirm differences in severity, with more severe classes having increased syndrome scale and decreased competency scale CBCL scores. Clinically significant impairment was found for severe inattentive and combined subtypes and the mild combined subtype. Overall, the presence of comorbid CD, ODD, or MD did not result in increased ADHD subtype impairment. CBCL scores distinguish impairment in ADHD subtypes created through LCA. Comorbidity with CD, ODD, or MD does not significantly increase impairment among ADHD subtypes. The mild combined ADHD subtype represents a clinically significant but under-studied form of ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/classificação , Doenças em Gêmeos/classificação , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Criança , Comorbidade , Transtorno da Conduta/epidemiologia , Doenças em Gêmeos/diagnóstico , Doenças em Gêmeos/epidemiologia , Feminino , Humanos , Masculino , Missouri/epidemiologia , Reprodutibilidade dos Testes , Gêmeos Dizigóticos/genética , Gêmeos Dizigóticos/psicologia , Gêmeos Monozigóticos/genética , Gêmeos Monozigóticos/psicologia
20.
Twin Res Hum Genet ; 8(5): 459-66, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16212835

RESUMO

The prevalence and frequency of comorbidity of possible bipolar disorder was examined with attention-deficit hyperactivity disorder (ADHD) in a nonreferred population of twins. Children and adolescents aged 7 to 18 years with a history of manic symptoms were identified from a population-based twin sample obtained from state birth records (n = 1610). The sample was enriched for ADHD; however, there was also a random control sample (n = 466), which allowed a look at the population prevalence of the disorder. Juveniles with threshold or below threshold manic episodes were further assessed for comorbidity with Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) and population-defined ADHD subtypes (from latent class analysis) using Fisher's exact test. Nine juveniles who exhibited DSM-IV manic (n = 1), hypomanic (n = 2) or below threshold episodes (n = 6) were identified. The population prevalence of broadly defined mania in the random sample was 0.2%. The possible manic episodes showed significant comorbidity with population-defined severe combined and talkative ADHD subtypes. It can be concluded that there is a significant association of bipolar symptoms with two population-defined subtypes of ADHD. Episodes of possible bipolar disorders as defined by DSM-IV are uncommon in this nonreferred sample. Children and adolescents with ADHD appear to be only modestly at increased risk for bipolar disorders.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno Bipolar/complicações , Adolescente , Criança , Humanos
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