Autism: What is the Cause?
Parenthood appears to be all about feeling guilty. And when your child suffers from autism or an autism spectrum disorder (ASD), self-flagellating questions abound. Should we have had him/her vaccinated? Did I feed them the wrong foods? Should I have raised them differently? Did they inherit this from my family/my spouse’s family? Whose fault is it and is it mine? Combined with the challenges of caring for the affected child and meeting their unique needs, this worry and confusion can be overwhelming.
For this reason, many AITSE members have requested that we provide an article on the causes of autism. And since ASDs are on the rise, having only been diagnosed in 0.04% of the population just 40 years ago, but now affecting between 0.3 and 0.66 % of people, a careful analysis of the possible causes is definitely warranted. Doubtless, some of this increase is due to improvements in diagnostic techniques, but that is unlikely to be the entire explanation for a tenfold hike in incidence of ASDs.
A review of the literature soon reveals that the reason for confusion about the cause of ASDs is simply that the exact cause is unknown. In addition, it is very likely that there is not just one cause, but that ASDs are the result of the unfortunate interaction of a number of factors, just like Type I diabetes, which can also be caused by a combination of heredity and lifestyle. Similarly, SA Currenti, the author of a recent review of the latest peer-reviewed literature published in Cell Mol Neurobiol suggests that ASDs are the result of genetic susceptibilities working together with various environmental factors. (They cover infection, toxins, vitamins, and vaccination.) A 2011 article in Evolutionary Psychology presents another viewpoint: that ASDs may be a result of the natural selection of “solitary foragers.”
Heredity/Genetic Factors: Research does indicate that there is a genetic basis for ASDs, but that it is probably multifactorial. Much work is now concentrated on rare mutations that affect the protein mecp2. This protein is highly expressed in neurons (there is a lot of it in nerve cells) and is important in turning off genes (~cellular instructions). It appears that some ASD patients cannot turn off the genes that are controlled by mecp2 class proteins. Interestingly, this protein is encoded on the X-chromosome, possibly explaining why ASDs occur in males four times more frequently than in females and sometimes appear to be inherited through the mother. However, it is important to realize that, although the evidence indicates that there is a genetic basis to ASDs, this cannot be the whole story. After all, evolution (changes in the genome) cannot explain the exponential increase in the number of diagnosed cases over the last 15 years–evolution simply does not happen that fast.
Infection: Genetic studies on the families of children with ASDs have revealed a possible correlation between autism and immune system dysfunction. First, some research, as yet inconclusive, suggests that mothers of children with ASDs may be producing antibodies against the fetal brain. Other work appears to show that maternal respiratory, vaginal, urinary, or flu infection during pregnancy, particularly when fever is present, may increase the risk of the child developing ASDs. Both infection and the use of tylenol (a pregnancy category B drug) change maternal and fetal levels of IL-6 (a chemical vital to central nervous system development), but more work is required before any certainty about a causative relationship between infection, treatment of that infection and ASDs is possible.
Vaccination: The April AITSE newsletter featured an article on the exposure of fraudulent studies published by Dr. Andrew Wakefield connecting MMR vaccination with autism. Certainly, the timing appeared right for this to be a real causative agent. After all, the symptoms of ASDs appear at the same age as the MMR vaccine is given. In addition, the exponential increase in children with ASDs has occurred over the same time frame as an increase in vaccination with MMR. However, coincidence does not mean causation. In fact, Dr. Wakefield’s research has since been discredited, even though he continues to protest his innocence, referring the reader to peer-reviewed articles that he says back his work. Unfortunately, a quick review of these articles reveal that they document a correlation between ASDs and digestive problems, not ASDs and vaccination. (Incidentally, the link between ASDs and gastrointestinal problems is also under debate.) Those AITSE members desiring more information are referred to this balanced and well-referenced article on the risks and benefits of individual vaccines.
Mercury/Thimerosal: Where there may be a correlation between ASDs and vaccination is in the use of preparations that contain thimerosal (approximately 50% mercury) as a preservative. It has been shown that autistic children have an intrinsic deficit in mercury excretion. This may be exacerbated by the fact that on average they use more antibiotics, which additionally reduce mercury excretion. As a result, children with ASD have double the amount of mercury in their baby teeth (a way to measure long term exposure). Note that this does not elucidate whether increased levels of mercury are a cause or a consequence of ASDs. However, some research does show that overdoses of mercury lead to neurological deficits and autistic symptoms, so there may be a causative link. And, when all the above is added to the fact that thimerosal was often used as a preservative in vaccine preparations (still is in the multi-dose influenza vaccine), leading to children being exposed many times the EPA recommended dosage of mercury, the idea that vaccination may be a causative agent in the development of autism does not seem so outlandish.
Vitamins/Folic Acid: At about the same time as the numbers of diagnosed cases of ASD began to rise, physicians began to prescribe use of folic acid supplements to all pregnant mothers. Since folate reduces the incidence of spina bifida by 70%, this is a good thing. However, it has also been shown that many children with ASDs have a reduced ability to utilize folic acid because of a mutation in gene for the MTHFR enzyme. Since folic acid supplementation stops at birth, it has been hypothesized that these children, who would have been miscarried had their mothers not used folic acid during pregnancy, end up at risk for later development of ASDs because folic acid supplementation often ceases at birth.
Interestingly enough, another supplement that has been investigated with regard to its possible role in ASDs is vitamin D. Several research groups have shown that vitamin D plays a role in neural development and assert that deficiencies are harmful in many ways. Since 90% of our vitamin D comes from skin exposed to sunlight, the post-1989 warning to mothers to keep their children out of the sun may have come with an unintentional side-effect of increasing the children’s risk for development of ASDs. The fact that autism occurs more frequently in African Americans, where 96% have insufficient vitamin D levels, than in Caucasians, where 37% have enough vitamin D, adds weight to the hypothesis. It is also interesting to realize that females are more efficient in making vitamin D than males (and males have a higher frequency of ASDs), but of course correlation does not mean causation.
Natural Selection/Evolution: What about evolution? The hypothesis by University of Southern California doctoral student Jared Reser is that autism may have evolved as human ancestors searched for food as “solitary foragers” during times of food scarcity. Basically, he is equating ASDs with introversion (the validity of this assumption is questionable) and says this tendency could have been adaptive. He claims that it is not so now because times have changed and modern mothers feed their children. Therefore, they are not forced to use their maladaptive tendencies towards repetitive behavior in a positive way, like finding food. In addition, in modern society we “cage” children with ASDs in a “confining environment” (school), thus resulting in self-injurous behavior. He appears to allege that those with ASDs would be better off roaming the plains in search of food.
Jared is writing his first paper as a doctoral candidate and so, should be given credit for a very imaginative hypothesis. But, his professors should be held accountable for their lamentable lack of guidance. The young man then goes on to bury himself even deeper in the evolutionary psychology mumbo jumbo and begins to compare the behavior of those with ASDs with that of orangutans and the behavior of non-autistics with that of chimpanzees. He does give a disclaimer on page 221, saying that “no offense is intended towards autistic individuals in this comparison with orangutans,” but by then the reader is finding it hard to focus on his meaning for laughing at this poor student’s politically correct squirming.
At the beginning of the paper Jared says, “evolutionary perspectives on disease can elucidate pathophysiology and ultimately inform treatment strategy.” One hopes that the treatment strategy he is recommending is not to take those with ASDs out of school and make them forage for their own food!
Seriously, it is evident from the above that ASDs probably are caused by a combination of at least one, and probably more, genetic and several environmental factors. Evolution does not make significant changes over the space of 20 years, and so the genetic factors have probably been around for a long time. Therefore, to reverse the current exponential increase of ASD cases, we need to concentrate on elucidation of the environmental factors that can contribute to development of ASDs. For those of you contributing to autism research, AITSE suggests you ask some questions about just what it is they are working on. Those of you with loved ones who struggle with ASDs, feel free to read around for yourself (the review mentioned above is good) when deciding whether to take measures like avoiding giving them a flu vaccine, tuna and mercury containing foods, avoiding unnecessary antibiotics, giving a folic acid supplement, and spending some time in the sun. These measures have some basis in science, but which if any might be helpful has not really been elucidated.
The purpose of AITSE is to educate and increase integrity in science. One hopes that a possible “side effect” of this may be to give people some peace, as they are informed about the facts and realize that it is not their fault. Then they can concentrate on the job ahead: helping their precious child/relative to be all they can be, even with ASD.