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- Arora, M., et al.
(författare)
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Fetal and postnatal metal dysregulation in autism
- 2017
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Ingår i: Nat Commun. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Genetic and environmental factors contribute to the etiologies of autism spectrum disorder (ASD), but evidence of specific environmental exposures and susceptibility windows is limited. Here we study monozygotic and dizygotic twins discordant for ASD to test whether fetal and postnatal metal dysregulation increases ASD risk. Using validated tooth-matrix biomarkers, we estimate pre- and post-natal exposure profiles of essential and toxic elements. Significant divergences are apparent in metal uptake between ASD cases and their control siblings, but only during discrete developmental periods. Cases have reduced uptake of essential elements manganese and zinc, and higher uptake of the neurotoxin lead. Manganese and lead are also correlated with ASD severity and autistic traits. Our study suggests that metal toxicant uptake and essential element deficiency during specific developmental windows increases ASD risk and severity, supporting the hypothesis of systemic elemental dysregulation in ASD. Independent replication in population-based studies is needed to extend these findings.
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| 2. |
- Austin, C, et al.
(författare)
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Dynamical properties of elemental metabolism distinguish attention deficit hyperactivity disorder from autism spectrum disorder
- 2019
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 238-
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Tidskriftsartikel (refereegranskat)abstract
- Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are neurodevelopmental conditions of overlapping etiologies and phenotypes. For ASD, we recently reported altered elemental metabolic patterns in the form of short and irregular zinc and copper cycles. Here, we extend the application of these biomarkers of prenatal and early postnatal elemental metabolism to distinguish between individuals diagnosed with ADHD and/or ASD and neurotypical controls. We recruited twins discordant for ADHD, ASD and other neurodevelopmental diagnoses from national twin studies in Sweden (N = 74) diagnosed according to DSM-5 clinical consensus and standardized psychiatric instruments. Detailed temporal profiles of exposure to 10 metals over the prenatal and early childhood periods were measured using tooth biomarkers. We used recurrence quantification analysis (RQA) to characterize properties of cyclical metabolic patterns of these metals. Regularity (determinism) and complexity (entropy) of elemental cycles was consistently reduced in ADHD for cobalt, lead, and vanadium (determinism: cobalt, β = −0.03, P = 0.017; lead, β = −0.03, P = 0.016; and vanadium, β = −0.03, P = 0.01. Entropy: cobalt, β = −0.13, P = 0.017; lead, β = −0.18, P = 0.016; and vanadium, β = −0.15, P = 0.008). Further, we found elemental pathways and dynamical features specific to ADHD vs ASD, and unique characteristics associated with ADHD/ASD combined presentation. Dysregulation of cyclical processes in elemental metabolism during prenatal and early postnatal development not only encompasses pathways shared by ADHD and ASD, but also comprise features specific to either condition.
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| 4. |
- Caporale, N., et al.
(författare)
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From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375:6582
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Tidskriftsartikel (refereegranskat)abstract
- Convergent evidence associates exposure to endocrine disrupting chemicals (EDCs) with major human diseases, even at regulation-compliant concentrations. This might be because humans are exposed to EDC mixtures, whereas chemical regulation is based on a risk assessment of individual compounds. Here, we developed a mixture-centered risk assessment strategy that integrates epidemiological and experimental evidence. We identified that exposure to an EDC mixture in early pregnancy is associated with language delay in offspring. At human-relevant concentrations, this mixture disrupted hormone-regulated and disease-relevant regulatory networks in human brain organoids and in the model organisms Xenopus leavis and Danio rerio, as well as behavioral responses. Reinterrogating epidemiological data, we found that up to 54% of the children had prenatal exposures above experimentally derived levels of concern, reaching, for the upper decile compared with the lowest decile of exposure, a 3.3 times higher risk of language delay. © 2022 American Association for the Advancement of Science. All rights reserved.
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| 8. |
- de Water, E., et al.
(författare)
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Prenatal metal mixture concentrations and reward motivation in children
- 2022
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Ingår i: Neurotoxicology. - : Elsevier. - 0161-813X .- 1872-9711. ; 88, s. 124-133
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Tidskriftsartikel (refereegranskat)abstract
- Reward motivation is a complex umbrella term encompassing the cognitions, emotions, and behaviors involved in the activation, execution, and persistence of goal-directed behavior. Altered reward motivation in children is characteristic of many neurodevelopmental and psychiatric disorders. Previously difficult to operationalize, the Progressive Ratio (PR) task has been widely used to assess reward motivation in animal and human studies, including children. Because the neural circuitry supporting reward motivation starts developing during pregnancy, and is sensitive to disruption by environmental toxicants, including metals, the goal of this study was to examine the association between prenatal concentrations of a mixture of neurotoxic metals and reward motivation in children. We measured reward motivation by administering a PR test to 373 children ages 6–8 years enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) Study in Mexico City. Children were asked to press a response lever for a token reward; one press on the response lever was required to earn the first token and each subsequent token required an additional 10 lever presses. Maternal blood concentrations of lead, manganese, zinc, arsenic, cadmium, and selenium were measured using inductively-coupled plasma mass spectrometry during the 2nd and 3rd trimesters of pregnancy. We performed generalized Weighted Quantile Sum (gWQS) regression analyses to examine associations between the prenatal metal mixture and reward motivation; adjusting for child sex, birthweight and age; and maternal IQ, education, and socioeconomic status. The prenatal metal mixture was significantly associated with higher motivation as indicated by more lever presses (ß = 0.02, p < 0.001) and a shorter time between receiving the reinforcer and the first press (ß = 0.23, p = 0.01), and between subsequent presses (ß = 0.07, p = 0.005). Contributions of different metals to this association differed by trimester and child sex. These findings suggest that children with increased exposure to metal during the 2nd and 3rd trimesters of gestation demonstrate increased reward motivation, which may reflect a tendency to perseverate or hypersensitivity to positive reinforcement.
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| 9. |
- Gennings, C., et al.
(författare)
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Contrasting prenatal nutrition and environmental exposures in association with birth weight and cognitive function in children at 7 years
- 2020
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Ingår i: BMJ Nutrition, Prevention & Health. - : BMJ Publishing Group Ltd. - 2516-5542. ; 3:2, s. 162-171
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Tidskriftsartikel (refereegranskat)abstract
- Background Good nutrition is essential for individual health, a notion that is particularly true during pregnancy. We have used a nutrition index that measures the adequacy of one's diet relative to the unique nutritional needs of individuals due to, for example, their activity level, dietary restrictions, lifestyle and body size. The use of this personalised metric of dietary nutritiousness in the analysis of prenatal environmental exposures and developmental outcomes permits testing for potential mitigating effects of good nutrition. We also provide an analysis strategy for investigating the balance in beneficial food sources which are also the source of environmental toxicants. Methods A holistic measure of nutrition, My Nutrition Index (MNI), measures the nutrient quality (ie, 'nutritiousness') of a specified daily diet. MNI is calculated based on quantification of dozens of macronutrients and micronutrients that are specific to an individual's nutritional needs by incorporating dietary restrictions, subject characteristics, activity level and health behaviours. The Swedish Environmental, Longitudinal, Mother and child, Asthma and allergy Study is a Swedish pregnancy cohort, with prenatal endocrine disrupting chemicals (EDCs) exposure and dietary data available. This makes it possible to test for the potential mitigating effects of good nutrition on health and development effects in offspring from EDCs. Results Using prenatal Food Frequency Questionnaire data to construct an individual's MNI, the index was significantly and positively associated with important metabolic outcome (as measured by birth weight) and cognitive function at age 7 years (as measured by WISC IQ) in children when adjusted for covariates and prenatal concentrations of an EDC. In a stratified analysis of 'low' and 'high' fish consumption, a potential source of perfluoro-octanesulfonic acid (PFOS), the association between PFOS and birth weight was diminished in the high consumption group compared with the low consumption group. Conclusions Thus, MNI is evidently a metric of the general nutritiousness of daily diets and is useful in environmental health studies in representing the impact of good nutrition, even during pregnancy.
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