Autism Linked to Banned Chemicals

October 23, 2017 · Posted in Risk Factors · Comment 

boy with autismAn explanation for the increase in autism rates over the past few decades has remained elusive in the years since researcher Andrew Wakefield fabricated a link between the disorder and mercury in vaccinations that was eventually completely debunked.

In 2016, researcher Kristin Lyall of Drexel University’s A.J. Drexel Autism Institute published findings suggesting that high exposure during pregnancy to chemicals banned in the 1970s increased risk of an autism spectrum disorder.

The study looked at 1144 children born in southern California between 200 and 2003. Their mothers had participated in California’s Expanded Alphafetoprotein Prenatal Screening Program, intended to identify birth defects during pregnancy. Second trimester blood samples from these women could be used to determine to what extent their children were exposed to the chemicals while in utero. The researchers found an association between the highest exposure levels and later autism diagnoses.

Lyall and colleagues measured levels of two different classes of organochlorine chemicals: polychlorinated biphenyls (PCBs), used as lubricants, coolants, and insulators; and organochlorine pesticides (OCPs), including DDT, which was banned in 1972. All production of organochlorine chemicals was banned in the US in 1977, but they remain in the environment and are absorbed in the fat of animals that humans eat. According to Lyall, people in the US generally have detectable levels of organochlorine chemicals in their bodies.

The study revealed that exposure to two compounds in particular—PCB 138/158 and PCB 153—was linked to dramatically higher autism rates. Level of exposure is key to autism risk. Those children in the top 25 percentile of exposure were 79% and 82% more likely to have an autism diagnosis than those with the lowest levels of exposure, respectively.

High exposure to two other compounds, PCB 170 and PCB 180, increased autism risk by 50%.

The findings by Lyall and colleagues were published in the journal Environmental Health Perspectives.

Editor’s Note: Another study by Manish Arora and colleagues links autism risk to levels of lead, zinc and manganese absorbed in early life.

The myth that mercury in vaccines causes autism still lingers in our popular culture. Mercury is no longer used in vaccines, but autism rates are still increasing. Perhaps the new findings of a link between heavy metals and autism will help end the misinformation about the safety of vaccines and allow more parents to vaccinate their children without worry.

Dietary Supplements for Autism: Up-to-Date Research

October 20, 2017 · Posted in Potential Treatments · Comment 

supplements

A 2017 review article by Yong-Jiang Li and colleagues in the journal Frontiers in Psychiatry describes the current research on dietary supplements that may help improve symptoms of autism spectrum disorder.

Some of the most promising research was on vitamin D, folinic acid, and sulforaphane. Methyl B12 and digestive enzyme therapy had some positive effects, while gluten- and casein-free diets and omega-3 fatty acids did not seem to help improve autism symptoms.

Vitamin D

Li and colleagues described a randomized, controlled trial of vitamin D in 109 children with autism aged 3 to 10 years. The experimental group received doses of 300 IU/kg of body weight/day, not exceeding 5000 IU/day. By the end of the four-month study, vitamin D levels had significantly increased in the experimental group compared to the control group. Those who received vitamin D also showed significant improvement on all ratings of autism symptoms, which included general scales of autism symptoms and more specialized checklists that capture aberrant behavior and social responsiveness.

Folinic Acid

The review article also described a randomized double-blind placebo-controlled trial of folinic acid in 48 children with autism spectrum disorder and language impairment. Participants received high-dose folinic acid (2 mg/kg/day) or placebo for 12 weeks. Those who received folinic acid, a form of folic acid that can readily be used by the body, showed significant improvements in verbal communication and core autism symptoms compared to those who received placebo. Participants who tested positive for folate receptor alpha autoantibodies (FRAA), which disrupt the transportation of folate across the blood-brain barrier and are common in autism, showed greater improvements from taking folinic acid than those without this abnormality.

Sulforaphane

Sulforaphane is a phytochemical derived from cruciferous vegetables. It can create metabolic effects that resemble those of a fever, which can improve behavioral symptoms of autism. Sulforaphane also fights oxidative stress, inflammation, and DNA damage, which may play roles in autism. Li and colleagues described the first double-blind, placebo-controlled trial of sulforaphane treatment in 29 boys aged 13 to 17 years. The boys who received sulforaphane showed significant improvement in autism-related behavior, especially social interaction and communication, after 18 weeks compared to those who received placebo. Sulforaphane has low toxicity and is well tolerated. Read more

Antidepressant Use in Pregnancy Does Not Increase Autism Risk

August 29, 2017 · Posted in Current Treatments · Comment 

pregnant woman with a pillTwo large observational studies published in the journal JAMA in 2017 find no link between antidepressant use during pregnancy and risk of an autism spectrum disorder. Previous studies had suggested a link between the two, but may not have sufficiently accounted for confounding factors. In both new studies, autism rates did not differ between siblings exposed to antidepressants in utero and those who were not exposed.

One of the studies, by researcher Ayesha C. Sujan and colleagues, analyzed exposure to antidepressants in the first trimester and neurodevelopmental outcomes in almost 1.6 million Swedish children. Antidepressant use did slightly increase the chance of a preterm birth, but was not linked to autism spectrum disorder, attention-deficit hyperactivity disorder (ADHD), or small size of the fetus.

The researchers suggested that doctors and patients work together to decide how depression should be treated during pregnancy, based on severity of the depression, treatment history, and access to services.

The other study, by researcher Hilary K. Brown and colleagues, analyzed 36,000 births in Ontario, Canada and found no increased risk of autism spectrum disorder based on antidepressant exposure in utero. The study controlled for 500 characteristics such as mother’s education, age, and health history.

The journal JAMA Pediatrics also published a meta-analysis and review of 10 studies on the subject, finding that a woman’s history of psychiatric disorders weakened any link between antidepressant use during pregnancy and risk of autism spectrum disorder in her children. This implies that the underlying illness, not its treatment, may be responsible if there is any link between depression and autism. The meta-analysis was carried out by researcher Antonia Mezzacappa and colleagues.

Oxytocin Improves Facial Expressiveness in People with Autism

November 30, 2016 · Posted in Potential Treatments · Comment 

facial expressionsIn a new study by Keiho Owada and colleagues, 18 people with autism spectrum disorders had more neutral facial expressions and fewer surprised expressions than 17 typically developing people while interacting socially. Oxytocin, a hormone that promotes social bonding, was delivered to the autism group via a nasal spray for six weeks, and made the faces of the people with autism more expressive. Oxytocin also improved their reciprocity in social interactions and increased activity in the dorsomedial prefrontal cortex, as observed via functional magnetic resonance imaging (fMRI).

The study suggests not only that oxytocin can normalize facial expressions, but also that the counting of facial expressions on videos of social interactions can be used as a measure of social symptoms of autism. The research was presented at the 2016 meeting of the Society of Biological Psychiatry.

RTMS Improves Executive Function in Kids with Schizophrenia and Autism

February 10, 2016 · Posted in Current Treatments · Comment 

rTMSResearcher Stephanie Ameis reported at the 2015 meeting of the American Academy of Child and Adolescent Psychiatry that following repeated transcranial magnetic stimulation (rTMS), a treatment in which a magnetic coil placed over the scalp delivers electric pulses to the brain, children with schizophrenia and autism spectrum disorders showed improvements in executive function, including working memory. The rTMS treatment targeted the left dorsolateral prefrontal cortex.

“De Novo” Mutations in Dozens of Genes Cause Autism

July 3, 2015 · Posted in Genetics, Risk Factors · Comment 

mutations

Two studies that incorporated data from more than 50 labs worldwide have linked mutations in more than 100 different genes to autism. Scientists have a high level of statistical confidence that mutations in about 60 of those genes are responsible for autism. So-called de novo mutations (Latin for “afresh”) do not appear in the genes of parents without autism, but arise newly in the affected child. The mutations can alter whether the genes get “turned on” or transcribed (or not), leading to disturbances in the brain’s communication networks.

The studies led by Stephan Sanders and Matthew W. State appeared in the journal Nature in late 2014. The identified genes fall into three categories. Some affect the formation and function of synapses, where messages between neurons are relayed. Others affect transcription, the process by which genes instruct cells to produce proteins. Genes in the third category affect chromatin, a sort of packaging for DNA in cells.

Before the new studies, only 11 genes had been linked to autism, and the researchers involved expect to find that hundreds more are related to the illness.

Editor’s Note: This new research explains how autism could be increasing in the general population even as most adults with autism do not have children. It should also put to rest the idea, now totally discredited, that ingredients in childhood immunizations cause autism. It is clearer than ever that kids who will be diagnosed with autism are born with these mutations.

With these genetic findings, the search for new medications to treat this devastating illness should accelerate even faster.

Bottom line: Childhood immunizations don’t cause autism, newly arising mutations in the DNA of parents’ eggs or sperm do. However, parental behavior could put their children and others at risk for the measles and other serious diseases if they do not allow immunizations. The original data linking autism to immunization were fraudulent, and these new data on the genetic origins of autism provides the best hope for future treatments or prevention.

More Evidence N-Acetylcysteine Added to Risperidone Improves Irritability in Autism

June 24, 2015 · Posted in Current Treatments · Comment 

irritability in autism

We reported in 2014 that researchers Ahmad Ghanizadeh and Ebrahim Moghimi-Sarani had found that the over-the-counter nutritional supplement n-acetylcysteine (NAC) added to the atypical antipsychotic risperidone reduced irritability in autism more than placebo added to risperidone.

A randomized, double-blind, placebo-controlled clinical trial published by M. Nikoo and colleagues in Clinical Neuropharmacology in 2015 replicated these results. Forty children with autism disorders aged 4–12 years were randomized to receive either risperidone plus NAC or risperidone plus placebo. Risperidone doses were between 1 and 2 mg/day, and NAC doses were 600 to 900 mg/day. By the end of the 10-week study, those children who received NAC had significantly greater reductions in irritability and hyperactivity/noncompliance than those who received placebo.

Editor’s Note: Three placebo-controlled studies have supported the efficacy of NAC in autism. One 2012 study, by A.Y. Hardan in Biological Psychiatry, evaluated monotherapy with oral NAC. In the other two, NAC was added to treatment with risperidone.

No Evidence Chelation Therapy Can Treat Autism

June 19, 2015 · Posted in Current Treatments · Comment 

autistic kid

Some children with autism have been subjected to chelation therapy, which is used to remove heavy metals from the blood after poisoning. The rationale for using this therapy in autism was the discredited theory that autism resulted from mercury poisoning. A recent review of research on chelation therapy for autism by the Cochrane Collaboration, a nonprofit health research organization, found only one randomized controlled trial of chelation therapy, which had a flawed methodology and also found no evidence of a reduction in autism symptoms. This means there is no evidence that chelation therapy, which can lead to kidney failure or death, has any effect on autism symptoms. Based on the lack of evidence that the therapy has benefits for children with autism spectrum disorders, its great expense, and the dangers it poses, chelation therapy should not be prescribed as a treatment for autism.

Effect Size of Autism Treatments

November 21, 2014 · Posted in Current Treatments · Comment 

autistic boy

At the 2014 meeting of the American Academy of Child and Adolescent Psychiatry, Fung et al. presented a meta-analysis of treatments for autism that ranked them in terms of statistical effect size, ranging from 0.9 (large), to 0.5 to 0.8 (medium), to <0.4 (small). The only drug with a large effect size was risperidone, at 0.9. Most effect sizes were medium, including aripiprazole at 0.8 and N-acetylcysteine (NAC) at 0.7. Both clonidine and methylphenidate had effect sizes of 0.6, and tianeptine’s was 0.5.

Fung and colleagues noted that the first two on the list, the atypical antipsychotics risperidone and aripiprazole, often have problematic side effects (such as sedation, weight gain, and motor symptoms) that must be balanced against their effectiveness. In contrast, NAC is well tolerated with few side effects, and two placebo controlled studies showed that it was effective both alone and as an adjunctive treatment to the antipsychotic risperidone.

In Mice, Autism-Like Behavior Connected to Problems Pruning Dendritic Spines

September 11, 2014 · Posted in Neurobiology · Comment 
spines on a dendrite

Spines on a dendrite

Autism spectrum disorders are associated with developmental abnormalities at excitatory synapses. Dendrites, the branched projections of neurons where electrical signals are passed from one cell to the next, are covered in hundreds to thousands of spines that facilitate the synaptic connections with other neurons. These spines are created and also pruned as part of normal learning and development.

Post-mortem examination of the brains of patients with autism spectrum disorders shows increased density of dendritic spines and less pruning in certain neurons in the temporal lobe. These examinations also show impaired mTOR autophagy. MTOR is a protein that plays a role in cell growth and survival. Autophagy is the normal process by which some components of cells are broken down.

A 2014 study by Guomei Tang et al. in the journal Neuron showed that mice that are genetically altered to have overactive mTOR also have reduced dendritic spine pruning, blockade of autophagy, and increased autism-like behaviors. An immunosuppressant drug called rapamycin inhibits mTOR, and treating the mice with this drug corrected the problems with spine pruning and the autism-like behaviors. (This was not true for mice who had been altered to have another type of autophagy.) Normal spine formation was not affected by the restored pruning ability.

Tang et al. concluded that mTOR autophagy plays an important role in dendritic spine pruning, and that restoring neuronal autophagy can correct synaptic abnormalities and restore normative social behavior in mice with hyperactive mTOR.

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