AHRQ

AHRQ / Time Trends

Diagnostic Substitution for Intellectual Disability: A Flawed Explanation for the Rise in Autism

Abstract

Time trends in autism spectrum disorder (ASD) and intellectual disability (ID) prevalence from the United States Individuals with Disabilities Education Act data were computed from 2000 to 2011 for each state and each age from 6 to 17. These trends did not support the hypothesis that diagnostic substitution for ID can explain the ASD rise over recent decades, although the hypothesis appeared more plausible when the data were aggregated across all states and ages. Nationwide ID prevalence declined steeply over the last two decades, but the decline was driven mainly by ~15 states accounting for only one-fourth of the U.S. school population. More commonly, including in the most populous states, ID prevalence stayed relatively constant while ASD prevalence rose sharply.

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  • June 6, 2017
AHRQ / Glial Cells / Males / Neurons / Toxicants

Gestational Exposure to Air Pollution Alters Cortical Volume, Microglial Morphology, and Microglia-Neuron Interactions in a Sex-Specific Manner

Excerpts:

“…several large scale epidemiological studies have recently linked prenatal air pollution exposure with an increased risk of neurodevelopmental disorders such as autism spectrum disorder (ASD).”

“We have demonstrated that prenatal exposure to DEP in mice, i.e., to the pregnant dams throughout gestation, results in a persistent vulnerability to behavioral deficits in adult offspring, especially in males, which is intriguing given the greater incidence of ASD in males to females (∼4:1).”

“DEP exposure increased inflammatory cytokine protein and altered the morphology of microglia, consistent with activation or a delay in maturation, only within the embryonic brains of male mice…”

“Consistent with this hypothesis, we found increased microglial-neuronal interactions in male offspring that received DEP compared to all other groups. Taken together, these data suggest a mechanism by which prenatal exposure to environmental toxins may affect microglial development and long-term function, and thereby contribute to the risk of neurodevelopmental disorders.”

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  • May 31, 2017
AHRQ / Arsenic / Cadmium / Detoxification / Mercury / Thimerosal / Toxicants

Blood Mercury, Arsenic, Cadmium, and Lead in Children with Autism Spectrum Disorder.

Abstract
Environmental factors have been implicated in the etiology of autism spectrum disorder (ASD); however, the role of heavy metals has not been fully defined. This study investigated whether blood levels of mercury, arsenic, cadmium, and lead of children with ASD significantly differ from those of age- and sex-matched controls. One hundred eighty unrelated children with ASD and 184 healthy controls were recruited. Data showed that the children with ASD had significantly (p < 0.001) higher levels of mercury and arsenic and a lower level of cadmium. The levels of lead did not differ significantly between the groups. The results of this study are consistent with numerous previous studies, supporting an important role for heavy metal exposure, particularly mercury, in the etiology of ASD. It is desirable to continue future research into the relationship between ASD and heavy metal exposure.

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  • May 8, 2017
AHRQ / Epidemiology / Preterm / Unvaccinated / Vaccine Schedule

Preterm birth, vaccination and neurodevelopmental disorders: a cross-sectional study of 6- to 12-year-old vaccinated and unvaccinated children

Excerpt:
“No association was found between preterm birth and NDD in the absence of vaccination, but vaccination was significantly associated with NDD in children born at term (OR 2.7, 95% CI: 1.2, 6.0). However, vaccination coupled with preterm birth was associated with increasing odds of NDD, ranging from 5.4 (95% CI: 2.5, 11.9) compared to vaccinated but non-preterm children, to 14.5 (95% CI: 5.4, 38.7) compared to children who were neither preterm nor vaccinated.”

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  • April 24, 2017
AHRQ / Folate / Methylation / Oxidative Stress / Transsulfuration

Classification and adaptive behavior prediction of children with autism spectrum disorder based upon multivariate data analysis of markers of oxidative stress and DNA methylation

Abstract
and psychometric tools. However, physiological measurements should support these behavioral diagnoses in the future in order to enable earlier and more accurate diagnoses. Stepping towards this goal of incorporating biochemical data into ASD diagnosis, this paper analyzes measurements of metabolite concentrations of the folate-dependent one-carbon metabolism and transulfuration pathways taken from blood samples of 83 participants with ASD and 76 age-matched neurotypical peers. Fisher Discriminant Analysis enables multivariate classification of the participants as on the spectrum or neurotypical which results in 96.1% of all neurotypical participants being correctly identified as such while still correctly identifying 97.6% of the ASD cohort. Furthermore, kernel partial least squares is used to predict adaptive behavior, as measured by the Vineland Adaptive Behavior Composite score, where measurement of five metabolites of the pathways was sufficient to predict the Vineland score with an R2 of 0.45 after cross-validation. This level of accuracy for classification as well as severity prediction far exceeds any other approach in this field and is a strong indicator that the metabolites under consideration are strongly correlated with an ASD diagnosis but also that the statistical analysis used here offers tremendous potential for extracting important information from complex biochemical data sets.

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  • March 16, 2017
AHRQ / C677T / Folate / Glutathione / Methionine / Methylation / MTHFR / Oxidative Stress / Transsulfuration

Classification and adaptive behavior prediction of children with autism spectrum disorder based upon multivariate data analysis of markers of oxidative stress and DNA methylation

Abstract
The number of diagnosed cases of Autism Spectrum Disorders (ASD) has increased dramatically over the last four decades; however, there is still considerable debate regarding the underlying pathophysiology of ASD. This lack of biological knowledge restricts diagnoses to be made based on behavioral observations and psychometric tools. However, physiological measurements should support these behavioral diagnoses in the future in order to enable earlier and more accurate diagnoses. Stepping towards this goal of incorporating biochemical data into ASD diagnosis, this paper analyzes measurements of metabolite concentrations of the folate-dependent one-carbon metabolism and transulfuration pathways taken from blood samples of 83 participants with ASD and 76 age-matched neurotypical peers. Fisher Discriminant Analysis enables multivariate classification of the participants as on the spectrum or neurotypical which results in 96.1% of all neurotypical participants being correctly identified as such while still correctly identifying 97.6% of the ASD cohort. Furthermore, kernel partial least squares is used to predict adaptive behavior, as measured by the Vineland Adaptive Behavior Composite score, where measurement of five metabolites of the pathways was sufficient to predict the Vineland score with an R2 of 0.45 after cross-validation. This level of accuracy for classification as well as severity prediction far exceeds any other approach in this field and is a strong indicator that the metabolites under consideration are strongly correlated with an ASD diagnosis but also that the statistical analysis used here offers tremendous potential for extracting important information from complex biochemical data sets.

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  • March 16, 2017
AHRQ / Autism Biomarkers / BDNF

Brain-Derived Neurotrophic Factor Levels in Autism: A Systematic Review and Meta-Analysis

Excerpt:

“A meta-analysis of blood BDNF in 887 patients with ASD and 901 control subjects demonstrated significantly higher BDNF levels in ASD compared to controls with the SMD of 0.47 (95% CI 0.07-0.86, p = 0.02). In addition subgroup meta-analyses were performed based on the BDNF specimen. The present meta-analysis study led to conclusion that BDNF might play role in autism initiation/ propagation and therefore it can be considered as a possible biomarker of ASD.”

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  • January 30, 2017

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