Autism is one of three disorders that falls under the umbrella of Autism Sprectrum Disorders (ASD). It is characterized by impaired communication and social skills and repetitive/restricted behaviours, all occurring prior to 3yrs of age. The other two disorders falling under the ASD are Asperger’s syndrome, which lacks the cognitive impairments present in autism, and Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS) which is diagnosed when all characteristics for either autism or Asperger’s are not present.
Autism rates worldwide have steadily increased since the 1980’s, although there is controversy as to whether this represents an actual increase in the occurrence of the disorder, or improved diagnostics. Nevertheless, the cause of autism remains unclear and is likely due to a multitude of genetic and environmental factors, that differ between individuals. First, let’s dispel the elephant in the room. Because the symptoms of autism begin to present at approximately the same time as the child’s MMR vaccination, the blame turned to the vaccine. Unfortunately, this theory was bolstered by Andrew Wakefield, who published a paper in The Lancet in 1998 suggesting that there was a link between the MMR vaccine and autism. This paper has since been retracted and Wakefield’s work has been called by some “an elaborate fraud”, involving misreporting of data, unethical treatment of subjects (children in this case), and conflicts of interest. What’s sad is that all of this caused many parents to stop vaccinating their children, leading to a resurgence in the occurrence of measles, resulting in preventable deaths. ANYWAYS, this could be a whole post on its own, so I’ll move on.
It is well known that factors in our environment (be it pollution, nutritional intake, physical activity, etc.) can alter normal functions of some of our genes, thereby producing phenotypic (ie. traits that we can see such as morphology, development, behavior, etc) differences. Nutritional factors play a huge role in the normal functioning of our genes, and therefore deficiencies or excesses can cause abnormal gene products to be produced. There is some indirect evidence that nutritional factors may play a role in the development of autism. The potential role of two of these factors, folic acid and vitamin D, were the subject of a review paper (cited below), which also reviewed genetic abnormalities, the role of the immune system, and heavy metal effects.
Folic acid is a B vitamin important for many functions including DNA synthesis and repair, and the production of red blood cells. Perhaps its most well-known role is that of preventing neural tube defects (NTDs, specifically spina bifida) in the developing embryo. Approximately 20yrs ago health agencies began advising women of child-bearing age to take a folic acid supplement and this has resulted in a 70% decrease in the incidence of NTDs as well as a decrease in the severity of defects when they occur.
So, what does folic acid have to do with autism? Due to a genetic polymorphism (a difference in DNA sequence between individuals) autistic individuals tend to show 50% decreased activity of a certain enzyme (MTHFR) that is required to metabolize folate. So even if these children have a sufficient intake of folate in their diets, their ability to metabolize it is only 50% of normal, and therefore deficiency may occur. In a strange way, the push for women to pre-natally supplement with folate may have contributed to the increase in autism rates that seemed to begin around the same time. Without maternal folate supplementation, miscarriage rates of fetuses with the abnormal MTHFR enzyme would have been higher than that resulting from pre-natal folate supplementation. So more children with the decreased ability to metabolize folate survived, which may be linked to the increased occurrence of autism. So the suggestion is to supplement children with folate to ensure those with the abnormal MTHFR enzyme get enough to make up for the decreased ability to metabolize.
Vitamin D is another factor that may play a role in the development of autism in some individuals. Vitamin D plays many roles in the body such as growth and remodeling of bone, neuromuscular functions, decreasing inflammation, and affecting genes that are involved in cell survival and death. Vitamin D is also important for neural development as a regulator of cell division and up-regulator of neurotrophins, which are crucial to the development, survival, and function of neurons. The majority, 90% actually, of our vitamin D supply comes from sun exposure, rather than diet. UVB light causes the transformation of a precursor molecule in our skin into an inactive form of vitamin D which is then further processed by the liver and kidneys into the active form (also called calcitrol).
Due to rising skin cancer rates in the late 80’s, sun avoidance was being recommended, and it was around this time that autism rates began to increase. There is lots of indirect evidence suggesting that a decrease in vitamin D production may be linked to the development of autism. Estrogen can increase vitamin D metabolism into the active form, while testosterone can not, possibly explaining the greater prevalence of autism in boys compared to girls (4:1). Autism rates are also higher in African Americans vs caucasians. Darker skin requires a greater amount of UVB rays to produce sufficient amounts of vitamin D. Shockingly, one study carried out in the US found that only 37% of white women and 4% of black women had sufficient amounts of vitamin D during pregnancy. While possible mechanisms of vitamin D deficiency-induced autism have not yet been shown, it is likely to again be due to a genetic polymorphism present in certain individuals. A candidate gene is CYP27B1, an enzyme that is required for the transformation of inactive vitamin D into its active form. A genetic polymorphism of this gene may lead to vitamin D deficiency, however the role this may have in the development of autism has not been examined yet.
So, in summary, both folic acid and vitamin D deficiency may contribute to the increase in autism seen in the past 20yrs or so. While potential mechanisms have not yet been verified, it is likely that some autistic individuals carry genetic polymorphisms resulting in a decreased activity of enzymes involved in the normal functioning of these important vitamins. While the indirect evidence is very interesting and indeed warrants further investigation, it is important to note that as of yet there is no direct evidence of these theories. Even if one or both of these theories are verified, they will only explain a proportion of cases, since there are many autistic children who do not show, or never have shown, deficiencies of either of these vitamins. It has proven difficult to determine a single mechanism, gene, or environmental factor responsible for the development of autism and therefore there is likely a variety of different factors, that when expressed alone or in combination with each other, in the “right” embryonic and genetic environment, lead to children who will be at higher risk of developing neurological disorders.
Citation: Currenti SA. Understanding and Determining the Etiology of Autism. Cell Mol Neurobiol (2010) 30:161–171. DOI 10.1007/s10571-009-9453-8