Fetal and postnatal metal dysregulation in autism : Nature Communications

 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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Variation in an Iron Metabolism Gene Moderates the Association Between Blood Lead Levels and Attention-Deficit/Hyperactivity Disorder in Children. - PubMed - NCBI

Although attention-deficit/hyperactivity disorder (ADHD) is a heritable neurodevelopmental condition, there is also considerable scientific and public interest in environmental modulators of its etiology. Exposure to neurotoxins is one potential source of perturbation of neural, and hence psychological, development. Exposure to lead in particular has been widely investigated and is correlated with neurodevelopmental outcomes, including ADHD. To investigate whether this effect is likely to be causal, we used a Mendelian randomization design with a functional gene variant. In a case-control study, we examined the association between ADHD symptoms in children and blood lead level as moderated by variants in the hemochromatosis (HFE) gene. The HFE gene regulates iron uptake and secondarily modulates lead metabolism. Statistical moderation was observed: The magnitude of the association of blood lead with symptoms of ADHD was altered by functional HFE genotype, which is consistent with a causal hypothesis."



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Variation in an Iron Metabolism Gene Moderates the Association Between Blood Lead Levels and Attention-Deficit/Hyperactivity Disorder in Children. - PubMed - NCBI

Although attention-deficit/hyperactivity disorder (ADHD) is a heritable neurodevelopmental condition, there is also considerable scientific and public interest in environmental modulators of its etiology. Exposure to neurotoxins is one potential source of perturbation of neural, and hence psychological, development. Exposure to lead in particular has been widely investigated and is correlated with neurodevelopmental outcomes, including ADHD. To investigate whether this effect is likely to be causal, we used a Mendelian randomization design with a functional gene variant. In a case-control study, we examined the association between ADHD symptoms in children and blood lead level as moderated by variants in the hemochromatosis (HFE) gene. The HFE gene regulates iron uptake and secondarily modulates lead metabolism. Statistical moderation was observed: The magnitude of the association of blood lead with symptoms of ADHD was altered by functional HFE genotype, which is consistent with a causal hypothesis.

Lead exposure in mothers can affect future generations -- ScienceDaily

It's a known fact that babies in the womb can be affected by low levels of lead exposure. If a pregnant woman is exposed to lead, the lead passes through the placenta into the baby's developing bones and other organs. Pregnant women with a past exposure to lead can also affect the unborn child's brain, causing developmental problems later in life. Previous research studies have suggested that exposure to heavy metal toxicants can influence a person's global DNA methylation profile.

In the recent Wayne State study led by Douglas Ruden, Ph.D., professor in the Department of Obstetrics & Gynecology and the Institute of Environmental Health Sciences, director of epigenomics, and program leader in the Center for Urban Responses to Environmental Stressors, he and his research team revealed that lead exposure can cause specific changes in DNA methylation, which can be detected in dried blood spots beyond one generation. The neonatal blood spots from both the mothers and children in this study were obtained from the Michigan Neonatal Biobank, a unique resource that has most of the neonatal dried blood spots from children born in Michigan since 1984.

Lead in kids’ blood linked with behavioral and emotional problems

Emotional and behavioral problems show up even with low exposure to
lead, and as blood lead levels increase in children, so do the
problems, according to research funded by the National Institute of
Environmental Health Sciences (NIEHS), part of the National Institutes
of Health. The results were published online June 30 in the journal
JAMA Pediatrics.

“This research focused on lower blood lead levels than

most other studies and adds more evidence that there is no safe lead
level,” explained NIEHS Health Scientist Administrator Kimberly Gray,
Ph.D. “It is important to continue to study lead exposure in children
around the world, and to fully understand short-term and long-term
behavioral changes across developmental milestones. It is
well-documented that lead exposure lowers the IQ of children.” 

Blood lead concentrations measured in more than 1,300
preschool children in China were associated with increased risk of
behavioral and emotional problems, such as being anxious, depressed, or
aggressive. The average blood lead level in the children was 6.4
micrograms per deciliter.

Here's the paper:-

Blood Lead Concentrations and Children’s Behavioral and Emotional ProblemsA Cohort Study

Lead in ancient Rome’s city waters

Thirty years ago, Jerome Nriagu argued in a milestone paper that Roman civilization collapsed as a result of lead poisoning. Clair Patterson, the scientist who convinced governments to ban lead from gasoline, enthusiastically endorsed this idea, which nevertheless triggered a volley of publications aimed at refuting it. Although today lead is no longer seen as the prime culprit of Rome’s demise, its status in the system of water distribution by lead pipes (fistulæ) still stands as a major public health issue. By measuring Pb isotope compositions of sediments from the Tiber River and the Trajanic Harbor, the present work shows that “tap water” from ancient Rome had 100 times more lead than local spring waters.

Prenatal exposure to environmental contaminants and behavioural problems at age 7-8years.

Animal studies showed that the developing brain is particularly
sensitive to chemical exposure. Human studies carried out in areas with
high exposures have proven neurodevelopmental disorders in relation to
e.g. lead and PCBs. Whether these chemicals are associated with
behavioural problems in childhood at current environmental levels is not
well known. Therefore, we assessed the association between prenatal
exposure to lead, cadmium, PCBs, dioxin-like compounds, HCB and p,p'-DDE
and behavioural problems in 7-8year old children. Prenatal exposure
data were obtained from the Flemish mother-new-born cohort. Lead,
cadmium, PCBs, dioxin-like compounds, HCB and p,p'-DDE were analysed in
cord blood. When the child reached 7-8years, 270 mothers completed the
Strengths and Difficulties Questionnaire assessing their children's
behavioural health. We found that doubling the prenatal lead exposure
(cord blood lead levels) was associated with a 3.43 times higher risk
for hyperactivity in both boys and girls. In addition, total
difficulties were 5.08 times more likely in the highest tertile for
prenatal lead exposure compared to the lowest tertile. In girls, total
difficulties were 4.92 more likely when doubling cord blood p,p'-DDE,
whereas no significant association was found in boys. Further, we noted
in boys a 1.53 times higher risk for emotional problems when doubling
cord blood cadmium, whereas no significant association was found in
girls. These results indicate that the presence of environmental
contaminants influences the mental health of the next generation.

Lead, mercury, and cadmium exposure and attention deficit hyperactivity disorder in children

 There is limited research examining the relationship between lead (Pb) exposure and medically diagnosed attention deficit hyperactivity disorder (ADHD) in children. The role of mercury (Hg) and cadmium (Cd) exposures in ADHD development is even less clear.

OBJECTIVES:

To examine the relationship between Pb, Hg, and Cd and ADHD in children living inside and outside a Lead Investigation Area (LIA) of a former lead refinery in Omaha, NE.

METHODS:

We carried out a case-control study with 71 currently medically diagnosed ADHD cases and 58 controls from a psychiatric clinic and a pediatric clinic inside and outside of the LIA. The participants were matched on age group (5-8, 9-12 years), sex, race (African American or Caucasians and others), and location (inside or outside LIA). We measured whole blood Pb, total Hg, and Cd using inductively coupled plasma mass spectrometry.

RESULTS:

Inside the LIA, the 27 cases had blood Pb geometric mean (GM) 1.89µg/dL and the 41 controls had 1.51µg/dL. Outside the LIA, the 44 cases had blood Pb GM 1.02µg/dL while the 17 controls had 0.97µg/dL. After adjustment for matching variables and maternal smoking, socioeconomic status, and environmental tobacco exposure, each natural log unit blood Pb had an odds ratio of 2.52 with 95% confidence interval of 1.07-5.92. Stratification by the LIA indicated similar point estimate but wider CIs. No associations were observed for Hg or Cd.

CONCLUSIONS:

Postnatal Pb exposure may be associated with higher risk of clinical ADHD, but not the postnatal exposure to Hg or Cd.

Infantile exposure to lead and late-age cognitive decline: Relevance to Alzheimer's Disease.`

BACKGROUND:

Early-life lead (Pb) exposure induces overexpression of the amyloid beta precursor protein and its amyloid beta product in older rats and primates. We exposed rodents to Pb during different life span periods and examined cognitive function in old age and its impact on biomarkers associated with Alzheimer's disease (AD).

METHODS:

Morris, Y, and the elevated plus mazes were used. Western blot, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay were used to study the levels of AD biomarkers.

RESULTS:

Cognitive impairment was observed in mice exposed as infants but not as adults. Overexpression of AD-related genes (amyloid beta precursor protein and β-site amyloid precursor protein cleaving enzyme 1) and their products, as well as their transcriptional regulator-specificity protein 1 (Sp1)-occurred only in older mice with developmental exposure to Pb.

CONCLUSIONS:

A window of vulnerability to Pb neurotoxicity exists in the developing brain that can influence AD pathogenesis and cognitive decline in old age.

Prenatal exposure to environmental contaminants and behavioural problems at age 7-8years.

Animal studies showed that the developing brain is particularly sensitive to chemical exposure. Human studies carried out in areas with high exposures have proven neurodevelopmental disorders in relation to e.g. lead and PCBs. Whether these chemicals are associated with behavioural problems in childhood at current environmental levels is not well known. Therefore, we assessed the association between prenatal exposure to lead, cadmium, PCBs, dioxin-like compounds, HCB and p,p'-DDE and behavioural problems in 7-8year old children. Prenatal exposure data were obtained from the Flemish mother-new-born cohort. Lead, cadmium, PCBs, dioxin-like compounds, HCB and p,p'-DDE were analysed in cord blood. When the child reached 7-8years, 270 mothers completed the Strengths and Difficulties Questionnaire assessing their children's behavioural health. We found that doubling the prenatal lead exposure (cord blood lead levels) was associated with a 3.43 times higher risk for hyperactivity in both boys and girls. In addition, total difficulties were 5.08 times more likely in the highest tertile for prenatal lead exposure compared to the lowest tertile. In girls, total difficulties were 4.92 more likely when doubling cord blood p,p'-DDE, whereas no significant association was found in boys. Further, we noted in boys a 1.53 times higher risk for emotional problems when doubling cord blood cadmium, whereas no significant association was found in girls. These results indicate that the presence of environmental contaminants influences the mental health of the next generation.

Lead acts to trigger schizophrenia in mutant DISC1 mice

 "Mice engineered with a human gene for schizophrenia (mutant DISC1) and exposed to lead during early life exhibited behaviors and structural changes in their brains consistent with schizophrenia. Scientists at Columbia University's Mailman School of Public Health and the Johns Hopkins University School of Medicine say their findings suggest a synergistic effect between lead exposure and a genetic risk factor, and open an avenue to better understanding the complex gene-environment interactions that put people at risk for schizophrenia and other mental disorders."

Blood Lead Levels High In 535,000 Kids In The USA

More than half-a-million children aged 1 to 5 years had blood lead levels higher than 5 µg/dL, the new threshold-for-concern, according to a Morbidity and Mortality Weekly Report issued by the CDC this week

See the unfortunate inventor Thomas Midgeley 

Higher levels of several toxic metals found in children with autism

 "In a recently published study in the journal Biological Trace Element Research, Arizona State University researchers report that children with autism had higher levels of several toxic metals in their blood and urine compared to typical children. The study involved 55 children with autism ages 5-16 years compared to 44 controls of similar age and gender."
The autism group had significantly higher levels of lead in their red blood cells (+41 percent) and significantly higher urinary levels of lead (+74 percent), thallium (+77 percent), tin (+115 percent), and tungsten (+44 percent). Lead, thallium, tin, and tungsten are toxic metals that can impair brain development and function, and also interfere with the normal functioning of other body organs and systems.

Women 16-49 at risk of multiple pollutants, which could harm brain development of fetuses and babies

In a recent study, more than half of women of childbearing age had median or higher levels of at least two of three pollutants that could harm brain development. Nearly 23 percent of American women of childbearing age met or exceeded the median blood levels for all three environmental chemical pollutants -- lead, mercury, and PCBs -- tracked in an analysis of data on thousands of women by Brown University researchers. All but 17.3 percent of the women aged 16 to 49 were at or above the median blood level for one or more of these chemicals, which are passed to fetuses through the placenta and to babies through breast milk.

EHP – Prenatal Methylmercury, Postnatal Lead Exposure, and Evidence of Attention Deficit Hyperactivity Disorder among Inuit Children in Arctic Québec

Prenatal exposure to methylmercury (MeHg) and polychlorinated biphenyls (PCBs) has been associated with impaired performance on attention tasks in previous studies, but the extent to which these cognitive deficits translate into behavioral problems in the classroom and attention deficit hyperactivity disorder (ADHD) remains unknown. By contrast, lead (Pb) exposure in childhood has been associated with ADHD and disruptive behaviors in several studies.

Objectives: This study examined the relation of developmental exposure to MeHg, PCBs, and Pb to behavioral problems at school age in Inuit children exposed from their traditional diet.

Methods: In a prospective longitudinal study conducted in the Canadian Arctic, exposure to contaminants was measured at birth and at school age. An assessment of child behavior (N = 279; mean age = 11.3 years) was obtained from the child’s classroom teacher on the Teacher Report Form (TRF) from the Child Behavior Checklist, and the Disruptive Behavior Disorders Rating Scale (DBD).

Results: Cord blood mercury concentrations were associated with higher TRF symptom scores for attention problems and DBD scores consistent with ADHD. Current blood Pb concentrations were associated with higher TRF symptom scores for externalizing problems and with symptoms of ADHD (hyperactive-impulsive type) based on the DBD.

Conclusions: To our knowledge, this study is the first to identify an association between prenatal MeHg and ADHD symptomatology in childhood and the first to replicate previously reported associations between low-level childhood Pb exposure and ADHD in a population exposed to Pb primarily from dietary sources.

Prenatal lead levels, plasma amyloid β levels, and gene expression in young adulthood.

Animal studies suggest that early-life lead exposure influences gene expression and production of proteins associated with Alzheimer's disease (AD).

OBJECTIVES:

We attempted to assess the relationship between early-life lead exposure and potential biomarkers for AD among young men and women. We also attempted to assess whether early-life lead exposure was associated with changes in expression of AD-related genes.

METHODS:

We used sandwich enzyme-linked immunosorbent assays (ELISA) to measure plasma concentrations of amyloid β proteins Aβ40 and Aβ42 among 55 adults who had participated as newborns and young children in a prospective cohort study of the effects of lead exposure on development. We used RNA microarray techniques to analyze gene expression.

RESULTS:

Mean plasma Aβ42 concentrations were lower among 13 participants with high umbilical cord blood lead concentrations (≥ 10 μg/dL) than in 42 participants with lower cord blood lead concentrations (p = 0.08). Among 10 participants with high prenatal lead exposure, we found evidence of an inverse relationship between umbilical cord lead concentration and expression of ADAM metallopeptidase domain 9 (ADAM9), reticulon 4 (RTN4), and low-density lipoprotein receptor-related protein associated protein 1 (LRPAP1) genes, whose products are believed to affect Aβ production and deposition. Gene network analysis suggested enrichment in gene sets involved in nerve growth and general cell development.

CONCLUSIONS:

Data from our exploratory study suggest that prenatal lead exposure may influence Aβ-related biological pathways that have been implicated in AD onset. Gene network analysis identified further candidates to study the mechanisms of developmental lead neurotoxicity.

Lead Poisoning In Children Significantly Reduced By Prenatal Remediation Strategy

An initiative in St. Louis targeted the homes of pregnant women to receive inspection and remediation of lead hazards before the birth of a child. According to a study just published in the American Journal of Obstetrics and Gynecology this measure prevented childhood lead poisoning and reduced the overall burden of lead toxicity in children.

In what ways does lead damage the brain?

Exposure to lead wreaks havoc in the brain, with consequences that include lower IQ and reduced potential for learning. But the precise mechanism by which lead alters nerve cells in the brain has largely remained unknown. Lead affects a growth factor , BDNF, modifying its transport. The researchers also explored how lead curbs production of BDNF in the cell nucleus. One factor, they say, may be a protein called methyl CpG binding protein 2, or MeCP2, which has been linked with RETT syndrome and autism spectrum disorders and acts to "silence" BDNF gene transcription.

Lead Levels In Lipstick Much Higher Than Previously Thought

A recent study conducted by the U.S Food And Drug Administration (FDA) reveals that over 400 popular lipstick brands contain twice as much lead as previously believed - up to 7.19 parts per million (ppm).

A Strategy for Comparing the Contributions of Environmental Chemicals and Other Risk Factors to Children's Neurodevelopment.

The contributions of methylmercury, organophosphate pesticides and lead to neurodevelopmental morbidity are substantial, exceeding those of many non-chemical risk factors.