The Role of Zinc and Copper in Autism Spectrum Disorders

Acta Neurobiol Exp 2013 2Children with Autism spectrum disorders (ASDs) appear to be at risk for zinc (Zn) deficiency, copper (Cu) toxicity, have often low Zn/Cu ratio, and often disturbed metallothionein (MT) system functioning. The evidence presented in this paper suggests that providing Zn to autistic children may be an important component of a treatment protocol, especially in children with Zn deficiency. It is important to monitor and follow the values for both Cu and Zn together during Zn therapy, because these two trace elements are both antagonists in function, and essential for living cells. 

The review article by Geir Bjørklund is published in Acta Neurobiologiae Experimentalis (2013; 73 (2): 225–236). This peer-reviewed journal is published by Nencki Institute of Experimental Biology in Warsaw, Poland.

 

Geir Bjørklund

The role of zinc and copper in autism spectrum disorders

Acta Neurobiol Exp (Wars) 2013; 73 (2): 225-236 

 

ABSTRACT

Autism spectrum disorders (ASDs) are a group of developmental disabilities that can cause significant social, communication and behavioral challenges. Several studies have suggested a disturbance in the copper (Cu) and zinc (Zn) metabolism in ASDs. Zinc deficiency, excess Cu levels, and low Zn/Cu ratio are common in children diagnosed with an ASD. The literature also suggests that mercury accumulation may occur as a cause or consequence of metallothionein (MT) dysfunction in children diagnosed with an ASD, which may be one of the causes of Zn deficiency. MTs are proteins with important functions in metal metabolism and protection. Zinc and Cu bind to and participate in the control of the synthesis of MT proteins. Studies indicate that the GABAergic system may be involved in ASDs, and that Zn and Cu may play a role in this system.

 

Exposure to high pollution levels during pregnancy may increase risk of having child with autism

AutismWomen in the U.S. exposed to high levels of air pollution while pregnant were up to twice as likely to have a child with autism as women who lived in areas with low pollution, according to a new study from Harvard School of Public Health (HSPH). It is the first large national study to examine links between autism and air pollution across the U.S.

“Our findings raise concerns since, depending on the pollutant, 20% to 60% of the women in our study lived in areas where risk of autism was elevated,” said lead author Andrea Roberts, research associate in the HSPH Department of Social and Behavioral Sciences.

The study appeared online June 18, 2013 in Environmental Health Perspectives.

Exposure to diesel particulates, lead, manganese, mercury, methylene chloride and other pollutants are known to affect brain function and to affect the developing baby. Two previous studies found associations between exposure to air pollution during pregnancy and autism in children, but those studies looked at data in just three locations in the U.S.

The researchers examined data from Nurses’ Health Study II, a long-term study based at Brigham and Women’s Hospital involving 116,430 nurses that began in 1989. Among that group, the authors studied 325 women who had a child with autism and 22,000 women who had a child without the disorder. They looked at associations between autism and levels of pollutants at the time and place of birth. They used air pollution data from the U.S. Environmental Protection Agency to estimate women’s exposure to pollutants while pregnant. They also adjusted for the influence of factors such as income, education, and smoking during pregnancy.

The results showed that women who lived in the 20% of locations with the highest levels of diesel particulates or mercury in the air were twice as likely to have a child with autism as those who lived in the 20% of areas with the lowest levels.

Other types of air pollution—lead, manganese, methylene chloride, and combined metal exposure—were associated with higher autism risk as well. Women who lived in the 20% of locations with the highest levels of these pollutants were about 50% more likely to have a child with autism than those who lived in the 20% of areas with the lowest concentrations.

Most pollutants were associated with autism more strongly in boys than girls. However, since there were few girls with autism in the study, the authors said this finding should be examined further.

Senior author Marc Weisskopf, associate professor of environmental and occupational epidemiology at HSPH, said, “Our results suggest that new studies should begin the process of measuring metals and other pollutants in the blood of pregnant women or newborn children to provide stronger evidence that specific pollutants increase risk of autism. A better understanding of this can help to develop interventions to reduce pregnant women’s exposure to these pollutants.”

 

Reference

Roberts AL, Lyall K, Hart JE, Laden F, Just AC, Bobb JF, Koenen KC, Ascherio A, Weisskopf MG. Perinatal air pollutant exposures and autism spectrum disorder in the children of Nurses’ Health Study II participants. Environmental Health Perspectives, online June 18, 2013.

 

1-in-50 U.S. school kids has autism: Gov’t survey

A government survey of parents says 1-in-50 U.S. schoolchildren has autism, surpassing earlier federal estimate for the disorder. Health officials say the new number doesn’t mean autism is occurring more often. But it does suggest that doctors are diagnosing autism more frequently, especially in children with milder problems. The earlier government estimate of 1-in-88 comes from a study that many consider more rigorous. It looks at medical and school records instead of relying on parents.

For decades, autism meant kids with severe language, intellectual and social impairments and unusual, repetitious behaviors. But the definition has gradually expanded and now includes milder, related conditions. The new report released on March 20, 2013 by the Centers for Disease Control and Prevention would mean at least 1 million children have autism. The number is important: Government officials look at how common each illness or disorder is when weighing how to spend limited public health funds. It’s also controversial.

The new statistic comes from a national phone survey of more than 95,000 parents in 2011 and 2012. Less than a quarter of the parents contacted agreed to answer questions, and it’s likely that those with autistic kids were more interested than other parents in participating in a survey on children’s health, CDC officials said. Still, CDC officials believe the survey provides a valid snapshot of how many families are affected by autism, said Stephen Blumberg, the CDC report’s lead author.

The study that came up with the 1-in-88 estimate had its own limitations. It focused on 14 states, only on children 8 years old, and the data came from 2008. Updated figures based on medical and school records are expected next year. “We’ve been underestimating” how common autism is, said Michael Rosanoff of Autism Speaks, an advocacy group. He believes the figure is at least 1-in-50.

There are no blood or biologic tests for autism, so diagnosis is not an exact science. It’s identified by making judgments about a child’s behavior. Physicians have been looking for autism at younger and younger ages, and experts have tended to believe most diagnoses are made in children by age 8. However, the new study found significant proportions of children were diagnosed at older ages.

Dr. Roula Choueiri, a neurodevelopmental pediatrician at Tufts Medical Center in Boston, said she’s seen that happening at her clinic. Those kids “tend to be the mild ones, who may have had some speech delays, some social difficulties,” she wrote in an email. But they have more problems as school becomes more demanding and social situations grow more complex, she added.

The greatest change in prevalence estimates was seen in boys and for adolescents aged 14 to 17 years old. Also, children who were first diagnosed in or after 2008 were more likely to have milder autism than those diagnosed in or before 2007, which may be because of increased awareness among parents and doctors and better diagnostic testing.

 

References 

Blumberg SJ, Bramlett MD, Kogan MD, Schieve LA, Jones JR. Changes in Prevalence of Parent-reported Autism Spectrum Disorder in School-aged U.S. Children: 2007 to 2011–2012. National Health Statistics Reports 2013; Number 65: 1-11.

Autism and Developmental Disabilities Monitoring Network Surveillance Year 2008 Principal Investigators; Centers for Disease Control and Prevention. Prevalence of autism spectrum disorders–Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2008. MMWR Surveill Summ. 2012; 61 (3): 1-19.

 

 

Autism Warning Signs

10 early warning signs of autismistockphoto “Could my child have autism?” With one in 88 children being diagnosed with autism, according to the CDC’s latest estimate, that’s what many new parents want to know. Autism is generally not diagnosed until age three, but signs of developmental delay can begin to appear as early as six months of age.

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Autism-spectrum disorders: 24 warning signs Pictures – CBS NewsView Autism-spectrum disorders: 24 warning signs photos in CBS News’ Autism-spectrum disorders: 24 warning signs photo gallery

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Folic acid supplements early in pregnancy may reduce child’s risk of autism by 40 percent

Large study in Norway finds early timing of supplements is critical:

JAMAPrenatal folic acid supplements appear to reduce the risk for autistic spectrum disorders, according to a study published today (February 13) in the Journal of the American Medical Association (JAMA).

The Centers for Disease Control and Prevention estimate that about 1 in 88 children in the U.S. have been identified with an Autism Spectrum Disorder (ASD). ASDs are amongst the most heritable of mental disorders, but little is known about how the disorder develops. Consequently, methods for diagnosis, prevention, and treatment are limited.

Folic acid (Vitamin B9) is required for DNA synthesis and repair in the human body, and its naturally occurring form—folate—is found in leafy vegetables, peas, lentils, beans, eggs, yeast, and liver. Taking folic acid supplements during early pregnancy is known to protect against spina bifida and other neural tube defects in children. In the United States, Canada, and Chile, folic acid is added to flour, so as to automatically provide these supplements to consumers. Norway does not enrich its flour, and since 1998, the Norwegian Directorate of Health has recommended that all women planning to become pregnant take a daily supplement of folic acid from one month before the start of pregnancy through the first trimester.

Despite this policy, studies from North America and Europe have shown that many pregnant women have a lower dietary intake of folate than what is necessary to prevent neural tube defects.

The report in JAMA emerged from the Norwegian Mother and Child Cohort Study (MoBa) and its sub-study of autism, the Autism Birth Cohort (ABC) Study. This international collaboration (see list of members below) comprises the largest prospective birth cohort devoted to the investigation of gene-environment interactions and biomarker discovery for neuropsychiatric disorders.

A total of 85,176 MoBa babies—born from 2002-2008—and their parents participated in the study. Prenatal dietary habits were recorded, and families were regularly surveyed for 3-10 years to measure the development of autism spectrum disorders. A total of 270 cases of autism spectrum disorders were identified in the study population (114 autistic disorder; 56 Asperger syndrome; 100 atypical or unspecified autism; i.e., pervasive developmental disorder not otherwise specified, PDD-NOS).

Mothers who took folic acid supplements in early pregnancy had a 40% reduced risk of having children with autistic disorder compared with mothers who did not take folic acid. The reduction in risk was observed in those who took folic acid during the time interval from 4 weeks before to 8 weeks after the start of pregnancy. Autistic disorder is the most severe form of autism spectrum disorders in children. No reduction in risk was observed for PDD-NOS. For Asperger syndrome, the number of children was too low to obtain sufficient statistical power in the analyses.

The use of folic acid in early pregnancy increased substantially from 2002 to 2008 among women who participated in MoBa. In 2002, 43% of mothers took folic acid supplements; by 2008, 85% of mothers did. However, many women began taking folic acid later than recommended, and only half started before the beginning of pregnancy.

The timing of a mother’s intake of folate appears to be a critical factor. Her child’s risk of autism was reduced only when the supplements were taken between 4 weeks before to 8 weeks after the start of pregnancy.

“We examined the rate of autism spectrum disorders in children born to mothers who did or did not take folic acid during pregnancy. There was a dramatic reduction in the risk of autistic disorder in children born to mothers who took folic acid supplements,” says Pål Surén, first author and epidemiologist at the Norwegian Institute of Public Health (NIPH).

The researchers also analyzed whether the risk of autistic disorder was influenced by the use of other dietary supplements. They did not find any association between the mother’s use of fish oil supplements (cod liver oil and omega-3 fatty acids) in early pregnancy and the risk of autistic disorder, and no association for the mother’s use of other vitamins and minerals.

In recent years, researchers have started to investigate whether folic acid has other beneficial effects on the development of the fetus’ brain and spinal cord. A study of language development from MoBa, published in 2011, showed that children whose mothers took folic acid supplements in early pregnancy had only half the risk of severe language delay at age three years compared with other children. A separate 2011 study from the University of California, Davis, demonstrated a lower risk of autism spectrum disorders in children of mothers who had used prenatal vitamin supplements during pregnancy. Prenatal vitamin supplements contain folic acid in combination with other vitamins and minerals.

Joint senior author Ezra Susser, professor of Epidemiology at Columbia University’s Mailman School of Public Health and professor of Psychiatry at the College of Physicians and Surgeons, stated, “Our findings extend earlier work on the significance of folate in brain development and raise the possibility of an important and inexpensive public health intervention for reducing the burden of autism spectrum disorders.”

“This elegant work illustrates the power of the ABC cohort for not only chipping away at the riddle of what causes autism, but for developing new methods for early recognition, prevention and treatment,” says W. Ian Lipkin, John Snow Professor of Epidemiology at the Mailman School of Public Health and principal investigator of the ABC cohort.

 

Reference

Surén P, Roth C, Bresnahan M, Haugen M, Hornig M, Hirtz D, Lie KK, Lipkin WI, Magnus P, Reichborn-Kjennerud T, Schjølberg S, Smith GD, Øyen AS, Susser E, Stoltenberg C. Association Between Maternal Use of Folic Acid Supplements and Risk of Autism Spectrum Disorders in Children. JAMA 2013; 309 (6): 570-577.

 

Prenatal folic acid supplementation associated with lower risk of autism

JAMAIn a study that included approximately 85,000 Norwegian children, maternal use of supplemental folic acid from 4 weeks before to 8 weeks after the start of pregnancy was associated with a lower risk of autistic disorder in children, according to a study appearing in the February 13 issue of JAMA.

“Supplementation with folic acid around the time of conception reduces the risk of neural tube defects in children. This protective effect has led to mandatory fortification of flour with folic acid in several countries, and it is generally recommended that women planning to become pregnant take a daily supplement of folic acid starting 1 month before conception,” according to background information in the article. It has not been determined whether prenatal folic acid supplements protect against other neurodevelopmental disorders.

Pal Surén, M.D., M.P.H., of the Norwegian Institute of Public Health, Oslo, and colleagues investigated the association between the use of maternal folic acid supplements before and in early pregnancy and the subsequent risk of autism spectrum disorders (ASDs) (autistic disorder, Asperger syndrome, pervasive developmental disorder-not otherwise specified [PDD-NOS]) in children. The study sample of 85,176 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study (MoBa). The children were born in 2002-2008; by the end of follow-up on March 31, 2012, the age range was 3.3 through 10.2 years (average age, 6.4 years). The exposure of primary interest was use of folic acid from 4 weeks before to 8 weeks after the start of pregnancy, defined as the first day of the last menstrual period before conception. Analyses were adjusted for maternal education level, year of birth, and parity (the number of live-born children a woman has delivered).

A total of 270 children (0.32 percent) in the study sample have been diagnosed with ASDs: 114 (0.13 percent) with autistic disorder, 56 (0.07 percent) with Asperger syndrome, and 100 (0.12 percent) with PDD-NOS. The researchers found that there was an inverse association between folic acid use and subsequent risk of autistic disorder. Autistic disorder was present in 0.10 percent (64/61,042) of children whose mothers took folic acid, compared with 0.21 percent (50/24,134) in children whose mothers did not take folic acid, representing a 39 percent lower odds of autistic disorder in children of folic acid users.

Characteristics of women who used folic acid within the exposure interval included being more likely to have college- or university-level education, to have planned the pregnancy, to be nonsmokers, to have a pre-pregnancy body mass index below 25, and to be first-time mothers.

“No association was found with Asperger syndrome or PDD-NOS, but power was limited. Similar analyses for prenatal fish oil supplements showed no such association with autistic disorder, even though fish oil use was associated with the same maternal characteristics as folic acid use,” the authors write.

The researchers note that the inverse association found for folic acid use in early pregnancy was absent for folic acid use in mid pregnancy.

“Our main finding was that maternal use of folic acid supplements around the time of conception was associated with a lower risk of autistic disorder. This finding does not establish a causal relation between folic acid use and autistic disorder but provides a rationale for replicating the analyses in other study samples and further investigating genetic factors and other biological mechanisms that may explain the inverse association,” the authors conclude.

 

Reference

Surén P, Roth C, Bresnahan M, Haugen M, Hornig M, Hirtz D, Lie KK, Lipkin WI, Magnus P, Reichborn-Kjennerud T, Schjølberg S, Smith GD, Øyen AS, Susser E, Stoltenberg C. Association Between Maternal Use of Folic Acid Supplements and Risk of Autism Spectrum Disorders in Children. JAMA 2013; 309 (6): 570-577.

 

Mad Child Disease (Lecture)

Is the autism epidemic a “mad child disease” linked to mercury? This lecture was presented by Boyd Haley, Ph.D. at the 22nd Annual Meeting of the Doctors for Disaster Preparedness held in San Diego, California; June 2004.

Evidence of Parallels Between Mercury Intoxication and the Brain Pathology in Autism

Although there may be genetic or developmental components to autism, the evidence in this current review of the brain findings in autism clearly indicates the reality of brain injury in Autism Spectrum Disorders (ASD); moreover, the brain injury symptoms which characterize autism closely correspond to those seen in sub-acute mercury (Hg) intoxication. The evidence presented in this paper is consistent with Hg being identified as either causal or contributory, working synergistically with other compounds or pathogens in producing the brain pathology observed in those diagnosed with ASD.

Their review article is published in Acta Neurobiologiae Experimentalis (2012; 72 (2): 113-153). This peer-reviewed journal is published by Nencki Institute of Experimental Biology in Warsaw, Poland. 

 

Janet K. Kern, David A. Geier, Tapan Audhya, Paul G. King, Lisa K. Sykes, and Mark R. Geier

Evidence of parallels between mercury intoxication and the brain pathology in autism

Acta Neurobiol Exp (Wars) 2012; 72 (2): 113-153 

 

ABSTRACT

The purpose of this review is to examine the parallels between the effects mercury intoxication on the brain and the brain pathology found in autism spectrum disorder (ASD). This review finds evidence of many parallels between the two, including: (1) microtubule degeneration, specifically large, long-range axon degeneration with subsequent abortive axonal sprouting (short, thin axons); (2) dentritic overgrowth; (3) neuroinflammation; (4) microglial/astrocytic activation; (5) brain immune response activation; (6) elevated glial fibrillary acidic protein; (7) oxidative stress and lipid peroxidation; (8) decreased reduced glutathione levels and elevated oxidized glutathione; (9) mitochondrial dysfunction; (10) disruption in calcium homeostasis and signaling; (11) inhibition of glutamic acid decarboxylase (GAD) activity; (12) disruption of GABAergic and glutamatergic homeostasis; (13) inhibition of IGF-1 and methionine synthase activity; (14) impairment in methylation; (15) vascular endothelial cell dysfunction and pathological changes of the blood vessels; (16) decreased cerebral/cerebellar blood flow; (17) increased amyloid precursor protein; (18) loss of granule and Purkinje neurons in the cerebellum; (19) increased pro-inflammatory cytokine levels in the brain (TNF-alppha, IFN-gamma, IL-1beta, IL-8); and (20) aberrant nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB). This review also discusses the ability of mercury to potentiate and work synergistically with other toxins and pathogens in a way that may contribute to the brain pathology in ASD. The evidence suggests that mercury may be either causal or contributory in the brain pathology in ASD, possibly working synergistically with other toxic compounds or pathogens to produce the brain pathology observed in those diagnosed with an ASD.

 

Biomarkers for Autism Discovered

An important step towards developing a rapid, inexpensive diagnostic method for autism has been taken by Uppsala University, among other universities. Through advanced mass spectrometry the researchers managed to capture promising biomarkers from a tiny blood sample. The study has just been published in the prestigious journal Nature Translational Psychiatry.

There are no acknowledged biomarkers for autism today. Researchers at Berzelii Centre and the Science for Life Laboratory in Uppsala who, in collaboration with colleagues at Linnaeus University in Sweden and the Faculty of Medicine in Tehran, Iran, who have discovered some promising biomarkers.

Many diseases are caused by protein alterations inside and outside the body’s cells. By studying protein patterns in tissue and body fluids, these alterations can be mapped to provide important information about underlying causes of disease. Sometimes protein patterns can also be used as biomarkers to enable diagnosis or as a prognosticating tool to monitor the development of a disease. In the current study disruptions of the nervous system were in focus when the scientists studied protein patterns in autism spectrum disorder (ASD).

To identify potential biomarkers (peptides or proteins), the researchers performed a detailed protein analysis of blood plasma from children with ASD compared with a control group. Using advanced mass spectrometric methods, they succeeded in identifying peptides consisting of fragments of a protein whose natural function is in the immune system, the complement factor C3 protein.

The study is based on blood samples from a relatively limited group of children, but the results indicate the potential of our methodological strategy. There is already a known connection between this protein and ASD, which further reinforces the findings, says Jonas Bergquist, professor of analytical chemistry and neurochemistry at the Department of Chemistry – BMC (Biomedical Centre) in Uppsala.

The hope is that this new set of biomarkers ultimately will lead to a reliable blood-based diagnostic tool.

 

Reference

Momeni N, Bergquist J, Brudin L, Behnia F, Sivberg B, Joghataei MT, Persson BL. A novel blood-based biomarker for detection of autismspectrum disorders. Transl Psychiatry (2012) 2, e91, doi:10.1038/tp.2012.19

 

Diet and Autism

Researcher Karl-Ludvig Reichelt and his colleagues at the National Hospital in Oslo have found that autistics have more peptides, or fragments of proteins in the urine than healthy people. The effect of this peptide accumulation is an opium-like effect in the brain. The autistics function better socially and achieve greater benefit from teaching and other stimulus when they eat a diet with low protein content without gluten and dairy products. The Norwegian nutrition physiologist Dag Viljen Poleszynski is also interviewed in this film. This is a trailer of the film FOOD? (2005).