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Billy Johnson, MD, Ph.D

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   Recent articles by
Billy Johnson, MD, Ph.D

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Childhood Autism on the Rise, Why? (Part 1)
by Billy Johnson, MD, Ph.D   
Rated "G" by the Author.
Last edited: Saturday, March 01, 2008
Posted: Wednesday, February 27, 2008

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Childhood Autism on the Rise?
Nowadays parents have genuine reason to be worried about a frightening disease whose cause is not known—autism. There is no telling whose young child will be next. Childhood autism is now found in about 1 in 150 children displaying a range of behaviors, including inability to socialize or expressing themselves. Could this disease too be linked to silent inflammation as a result of environmental causes like radiation, toxins and pesticides? The causes of autism remain under investigation with no clear data at the present time to identify the reasons that some children suffer from the disorder. Parts 1 & 2 of the article look at possible causes, and Part 3 & 4 will try to provide some basic common sense approaches to help a child with autism. Excerpt from "New Prescription for Childhood Obesity"

Childhood Autism on the Rise. Why? (Part 1)

Genetics versus Environmental Causes

Nowadays parents have genuine reason to be worried about a frightening disease whose cause is not known – autism. There is no telling whose young child will be next. Autism is a complex developmental disability that typically appears during the first three years of life and is characterized by a neurological disorder that affects the normal development of the brain, particularly in the areas of social interaction and communication skills. Childhood autism is now found in about 1 in 150 children displaying a range of behaviors, including inability to socialize or express themselves. About as many as 1.5 million Americans today are believed to have some form of autism. And this number is on the rise. It’s estimated that the prevalence of autism could reach 4 million Americans in the next decade.

Is autism linked to free radicals and oxidative stress triggered by environmental causes like poor diet and nutrition, including radiation, pollutants, toxins and pesticides? The causes of autism remain under investigation with no clear data at the present time to identify the reasons why some children suffer from the disorder. In this review, I will explore the possibility that autism is caused by a combination of genetic and environmental factors. Which of these factors explain the acute rise of autism?

Genetic Influences
Genes: Most experts speculate that genetic factors account for the most significant cause for autism. So much so that early studies estimated that genetic may be responsible for over 90% of childhood autism based on studies of twins. However, these studies have been challenged and most experts will say it’s an overestimation. Nevertheless, many studies have shown that parents with a family history of autism are more likely to have children with autism. Also many families with one autistic child are more likely to have more than one autistic child. The genetics of autism is complex and the results of several studies have been inconclusive. This is because the disease may require the expression of several genes that may interact with each other or with environmental factors in a complex way. Several suspected genes have been located, but the mutations that increase autism risk have yet to be identified.

The problem with the genetic factors is that our genes have not changed within the last thousands of years. Therefore, this alone cannot explain the rising incidence of childhood autism seen within the last decade. Is it possible that something else far ominous is going on here? Yes, there is – the environmental causes, which also coincides well with the rising incidence of adult diseases in young children, such as type 2 diabetes, heart disease, high blood pressure, and even inflammatory obesity. This is a trend never imagined fifteen to twenty years ago. To look for the real cause of childhood autism, one has to explore the environmental causes, including those involved in the prenatal environment, particularly, during the first eight weeks of pregnancy. I will try to explore this thesis in greater details later. For now keep in mind that genetic factors may play a role, but the environmental factors may even play a bigger role by turning on genes that express the autism spectrum disorders. In other words, without the intervention of external environmental causes, even a history of genetic predisposition may not increase risk of autism at such an alarming rate.

Environmental Influences. How Important are They?
Pre-prenatal Environment
Some studies have found an association between parental characteristics and autism, such as advanced maternal and paternal age. Older parents have a higher chance of having a child with autism. These associations may reflect environmental causes instead of a genetic cause, such as lifestyle choices, poor health with advanced age, obesity and physical inactivity. Other possibilities include recreational drugs, smoking and alcohol consumption before and during pregnancy could increase risk of autism as part of fetal alcohol syndrome or alcohol induced birth defects? This debate is ongoing.

Prenatal Environment
Chemical Agents
Childhood autism has been linked to birth defect agents acting during the first eight weeks of gestation when the fetus’s organs, including the brain are rapidly developing. The agents responsible are called teratogens – environmental agents that cause birth defects. These include exposure of the embryo to toxic agents like thalidomide, which was used as a sleeping pill and to treat morning sickness during pregnancy. The drug was banned in the 1960s after it was found to cause limb deformities in children of women who took the drug early in their pregnancy. Other drugs include valproic acid (antiepileptic agent), or misoprostol, which is used to prevent NSAID-induced gastric ulcers, or to induce labor as an abortifacient. It’s a synthetic prostaglandin analogue. Rubella infection in the mother has also been implicated. Fortunately, these cases are rare today.

Alcohol (grain alcohol), like whisky and vodka, has also been implicated to increase autism risk, as part of fetal alcohol syndrome or birth defects associated with alcohol consumption during pregnancy. Alcohol may act by inducing damaging free radicals and oxidative stress, including insulin resistance and silent low-grade inflammation. All known teratogens appear to act during the first eight weeks of gestation when the developing fetus is most vulnerable – suggesting the possibility that autism may be initiated or arises very early in fetal development. Agents and infections contracted in early pregnancy may adversely affect the development of the brain and nervous system more than agents and infections occurring in late pregnancy, like the second or third trimesters.

High Blood Sugar (Gestational Diabetes & Diabetes)
One crucial area involving the maternal environment that may have adverse effects on fetal brain development early in pregnancy is gestational diabetes or preexisting diabetes. The prevalence of this disease makes it worthy of serious attention. It’s estimated that 1 in 100 women of childbearing age has high blood sugar before getting pregnant. Another 5 percent of pregnant women develop high blood sugar during pregnancy making it one of the most common health problems in obstetrics. High blood sugar at conception and in the early eight weeks of pregnancy is strongly associated with serious birth defects, miscarriage and stillbirths. Is it possible that high blood sugar in early pregnancy could also increase risk of autism?

There are reasons to believe that it could. One explanation is that poorly controlled maternal diabetes may cause blood sugar to accumulate in the brain of the fetus causing oxidative stress and inflammation that damages brain cells and tissues. This scenario is similar to some of the complications seen in cases of high blood sugar or type 2 diabetes in adults in which there is a strong association to vascular inflammation such as arteriosclerosis and stroke that may cause Alzheimer’s or dementia by limiting blood flow to the brain. The damage caused by high blood sugar involves glycation – a process that is central to diabetes-related complications – the same process causing food to brown in an oven. Glycation is defined as the process in which sugar molecules react with proteins to produce damaging free radicals and inflammatory compounds in the body.

Glycation of glucose and proteins cause damage to healthy cells and their components (DNA, lipids, proteins, and cell membranes) causing an overwhelming production of free radicals and inflammatory hormones, that damage blood vessels and nerves, including brain cells. Perhaps, this process could cause autism, especially if it happens in the first eight weeks of conception when the embryo is very vulnerable. Furthermore, most women with irregular periods may not even be aware that they are pregnant until close to the eight week.

Due to the nature of diabetes, poorly controlled blood sugar during pregnancy may result in high levels of free radicals that cause oxidative stress, which is ultimately responsible for the damage caused by the disease. Both glycation and oxidative stress are central to understanding damage caused by diabetes-associated pregnancy. This is the rational for the need to increase the antioxidants levels in meals to help counteract oxidative stress and reduce diabetes-related complications, particularly during pregnancy which may expose the developing fetus to a very hostile environment. Unfortunately, most diabetes therapy is focused solely on lowering blood sugar, instead of addressing the possible root cause – glycation and oxidative stress.

However, there is good news for women contemplating pregnancy who are at risk for diabetes or gestational diabetes. In 1991, John L. Kitzmiller, M.D. and others at the University of California, San Francisco, showed that controlling blood sugar before pregnancy in women with previously high blood sugar significantly reduced the risk of birth defects. You can also protect yourself and your fetus by eating foods high in antioxidants and phytonutrients to help counteract damaging free radicals and oxidative stress.

Low Levels of Insulin-Like Growth Factor
In a new study, levels of insulin-like growth factor-1(IGF-1) — a key substance in brain development is low in young children with autism. IGF-1 is a substance that stimulates cell growth and differentiation both before and after birth. Scientists in Finland measured levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-2 (IGF-2) in the cerebrospinal fluid of 25 children with autism and 16 age-matched children without disabilities. The researchers found significantly reduced IGF-1 levels in autistic children less than five years of age, but not in older children. No differences in IGF-2 levels were seen between autistic children and controls, except that IGF-2 concentration was correlated with age in controls but not in the autistic children.

The researchers noted that cerebellar abnormalities of the brain are a consistent finding in autism, and that IGF-1 is crucial to the survival of Purkinje cells in the cerebellum. They therefore concluded that low levels of IGF-1 during the critical period of brain growth and differentiation might be insufficient to support normal Purkinje cell development. As a result, the early and critical development of the brain in autistic children is affected leading to autism.

These findings provides hope that in the near future, effective treatment will be available by administering IGF-1 early in development in order to increase the brain level of IGF-1.

Too Few Neurons in the Brain Controlling Emotions
In a 2006 study, scientists found fewer neurons in the amygdala of males with autism than non-disabled males. The amygdala is a region of the brain involved in memory and expressing emotions. The amygdala in autistic children appears to undergo an abnormal pattern of postnatal development that includes early enlargement and ultimately reduced number of neurons.

Folic Acid (Folate)
Folic acid is a B-vitamin taken during the early months of pregnancy to help prevent disabling or fatal birth defects of the brain and spine. Folic acid is also needed to make red blood cells, DNA, and chemical components of the nervous system. However, there are suggestions that folic acid taken during pregnancy might play a role in causing autism by modulating gene expression without affecting its DNA (through epigenetic mechanism). This is still a hypothesis.

Fetal Testosterone
The fetal testosterone theory suggests that elevated levels of testosterone in the amniotic fluid of pregnant mothers may cause the brain of the fetus to develop more towards “male” dominant traits (improved ability to see patterns and analyze complex systems) over “female” dominant traits emphasizing communication and empathy. Some investigators have published several reports suggesting that elevated levels of fetal testosterone could produce behaviors similar to those observed in autistic children. The studies are controversial and the idea that baby boys and girls respond differently to objects and people is contradicted by many other studies.

Ultrasound or sonogram is a very popular investigative and diagnostic tool that is widely used in obstetrics. There is no scientific evidence linking prenatal ultrasound exposure and autism, but the data on human fetal exposure during diagnostic ultrasound is limited. However, a controversial study in 2006 found that prolonged exposure of mouse embryos to ultrasound waves caused a small number of neurons to fail to acquire their proper orientation during neuronal migration. It is highly unlikely that fetal ultrasound increases risks of autism considering the number of fetal exposure during the first trimester in America and other developed countries.

Other Perinatal Environmental Factors
A 2007 review of risk factors for autism found an association with some perinatal and obstetric conditions:
•Low birth weight and post-date gestation
•Hypoxia (insufficient oxygen) during childbirth
•Premature infants who survived bleeding in the brain that injures the cerebellum (cerebellar hemorrhagic injury) were more likely to show symptoms of autism than controls without brain injury.
Parts 2,3 & 4 to foloow---keep checking.
Author of New Prescription for Childhood Obesity--Buy Now.


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Reviewed by Eileen Granfors 2/27/2008
Wow! Very informative. Some new interesting ideas to check out. My grandson has autism, and though he is responding to interactive and nutrional therapy, he is still non-verbal (30 months), and we are working with him as much as we can. He has a new baby sister. Eileen

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