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Charles Ives (insurance specialist and modern composer) wrote The Alcotts (right click to open in new tab) somewhere around 1911. It's his most accessible work, as he was one of the first experimenters with polytonal music - you'll hear some, but not too many, of the clashing polytones in this piece. He composed many melodies from the early 1900s right up until 1927, when one day he came downstairs and said he could compose no more. "Nothing sounds right." It is something of a tradition at my other blog to add music to the posts - hope you enjoy it.
And so we come round again to autism. The heartbreaking disorder where, in 30% of cases, children seem to be developing normally, only to regress and lose speech and language development somewhere between 18 and 36 months. It seems that in most children, the disorder is detectable very early with differences in gaze and response to social stimuli (1). The reason no one has been able to find a specific pathological cause or cure is because it is multifactorial - it seems that a combination of genetic, environmental, neurological, and inflammatory factors contribute to the development of autism. Today I would like to focus specifically on the inflammation and other evidence of nutritional contributing factors.
The best evidence of the actual inflammatory damage comes from the work of some neurologists and pathologists at Johns Hopkins. They were able to examine the (post-mortem) brains of several children and adults with autistic disorders, and also the spinal fluid obtained via spinal tap from autistic children and normal controls (2). They found that the most striking differences between autistic and normal brains were loss of the purkinje cell layer in the cerebellum, and also a marked activation of the microglia, which are cells in the central nervous system that are central to the inflammatory response.
The inflammatory response is our body's defense against invaders, our internal army, if you will. In autism, the army seems to be turned against itself. In their tests on spinal fluid, the researchers found elevations of many pro-inflammatory cytokines and chemoattractants for macrophages - cells that are called into action to eat and destroy invaders. It seems there is an inflammatory war going on in the brains of autistic children and adults, and the brain is the battleground.
Other studies have shown that autism is possibly an autoimmune disease of some kind (3). Only this autoimmune disease seems to work on susceptible developing brains, leading to the devastating consequences with which we are all too familiar. The word "autoimmune" means that the immune system is not only fighting external invaders or bad guys in the body, such as viruses, bacteria, or newly-formed cancer cells, but also has started to attack presumably healthy tissues of the body.
In the evolutionary medicine paradigm, autoimmune disorders are diseases of civilization, caused by our highly inflammatory diets and stressful lifestyles. And, indeed, this theory brings together the possible "bad guys" we've discussed already, gluten, casein, and then other issues with modern lifestyle that I will discuss specifically in future posts, such as insufficient vitamin D and poor micronutrition affecting brain health. I'm also pleased to say that after my first two "diet and autism" posts, a researcher has emailed me with some additional information and insights about gluten, casein, and suspected mechanisms, so I will be doing another post on that as well.
Epidemiological studies suggest that autoimmune disorders are much more common than normal in families of kids with autism. In addition, mothers with asthma, psoriasis, and type I diabetes were more likely to have autistic kids. Mothers diagnosed with asthma or allergies during the second trimester seem to have especially high risk, suggesting that a flare-up of autoimmune disease at a particular stage in fetal development might be causative. Epidemiologists at the Harvard School of Public Health did a meta-analysis of studies of prenatal risk factors and autism (4), and they found higher risk for mothers and fathers of "advanced" age, a two-fold increased risk among mothers with gestational diabetes, and also increased risk among mothers who had bleeding during pregnancy and psychiatric medication use (there are specific studies demonstrating an increased risk with depakote use during pregnancy and autism).
Inflammation, inflammation, inflammation. Psoriasis, for example, is associated with obesity (inflammation), gestational diabetes with insulin resistance and inflammation. All these diseases of civilization are floating around autism. All these diseases of civilization with multifactorial causes, genetic susceptibilities, and chronic management in lieu of cure. With associations, one never knows if one thing causes another or if a third issue is the cause for both, but associations should make one stand up and take notice, and look around for biologically plausible causations and ways to figure out, precisely, what is going on.
Is there other evidence that nutritional issues could possibly cause autism? The modern diet with an excess of processed food is paradoxical - it leads to obesity with too many calories, yet is nutritionally poor with respect to minerals, certain vitamins, and possibly even some amino acids needed for optimal brain health.
Well, a paper did come out in early 2011 with an intriguing link between autism and nutrition: Closely Spaced Pregnancies are Associated with Increased Odds of Autism in California Sibling Births. It is not direct evidence by any means, but it is striking.
Briefly, the researchers matched every single sibling birth in California from 1992-2002 with reports of getting services for autism, spent a good deal of time on the statistics and did a secondary case-controlled study to make sure they weren't missing anything. It turns out that the odds of a second child born within about 18 months of a first child (that is, an 'interpregnancy interval" or the time between pregnancies of 12 months or less) have more than a 3 fold risk of having autism than a second child born more than 3 years after the first one. Risk for second children born at interpregnancy intervals of between 12 and 36 months were middling, but risk rose abruptly at 0-12 months.
The researchers in this paper spent a great deal of time reviewing the statistics and making sure every last variable was accounted for (including age of mother, previous children with autism, age of father, education of everyone, etc.). They didn't spend a lot of time trying to figure out why the pregnancy interval timing would matter in the discussion, but they did briefly mention possible depletion of folate, omega 3 fatty acids, or stress (it is, obviously, very stressful to have a young baby and to be pregnant at the same time).
Since, during pregnancy, the fetus will tend to suck whatever nutrients are needed straight from mama, whether she can spare them or not, it is sensible that a nutritional explanation could account for the increased risk of autism in second children when the pregnancies are closely spaced. By nutrition, I mean anything from deficiencies in omega 3 fatty acids, to minerals such as zinc, magnesium or selenium, or depletion of the B vitamins, including folic acid. My suspicion is that small differences in nutritional status can increase risk at vulnerable times in the development of the fetus. The absolute causes, however, are yet to be discovered.
Here is a free, online, up to date, and comprehensive review of pregnancy, nutrition, and birth outcomes - if you are interested. This link is to a free full text academic paper entitled "Maternal Nutrition and Birth Outcomes" by Kathleen Abu-Saad and Drora Fraser.
My ultimate preventative solution is, of course, to make sure that moms-to-be out there are consuming nutrient rich diets with plenty of folate, phospholipids, minerals, omega 3s, etc. etc. etc. Eat real food, and have fun. Get some sunshine (don't get burned), and restful sleep. Not such a bad health prescription, is it? With all those variables, a proper study will never be done. But then, seems a safe enough thing to recommend, and our health is in our hands.
More articles like this one at Evolutionary Psychiatry
Copyright Emily Deans, M.D.
