First off, it is often terribly hard to detangle environmental from genetic from random forces in any complex system, but even more so in people where every one of us has a unique genetic profile, a unique environmental history, and a complex interaction with the world around us. Right out the gate you are in a sample size of one.
Then anything biochemical / medical has to deal with the interacting complexity of that genetics with methylation of some genes, turning them on or off in response to the environment or sometimes inherited methylation.
In biological systems, methylation is catalyzed by enzymes; such methylation can be involved in modification of heavy metals, regulation of gene expression, regulation of protein function, and RNA processing. (Methylation of heavy metals can also occur outside biological systems.) Chemical methylation of tissue samples is also one method for reducing certain histological staining artifacts. The counterpart of methylation is demethylation.
Human DNA has about 80–90% of CpG sites methylated, but there are certain areas, known as CpG islands, that are GC-rich (high guanine and cytosine content, made up of about 65% CG residues), wherein none are methylated. These are associated with the promoters of 56% of mammalian genes, including all ubiquitously expressed genes. One to two percent of the human genome are CpG clusters, and there is an inverse relationship between CpG methylation and transcriptional activity. Methylation contributing to epigenetic inheritance can occur through either DNA methylation or protein methylation. Similarly, RNA methylation occurs in different RNA species viz. tRNA, rRNA, mRNA, tmRNA, snRNA, snoRNA, miRNA, and viral RNA. Different catalytic strategies are employed for RNA methylation by a variety of RNA-methyltransferases. RNA methylation is thought to have existed before DNA methylation in the early forms of life evolving on earth. N6-methyladenosine (m6A) is the most common and abundant methylation modification in RNA molecules (mRNA) present in eukaryotes. 5-methylcytosine (5-mC) also commonly occurs in various RNA molecules. Recent data strongly suggest that m6A and 5-mC RNA methylation affects the regulation of various biological processes such as RNA stability and mRNA translation, and that abnormal RNA methylation contributes to etiology of human diseases.
So good luck trying to sort out all that whirring machinery with just one or two samples of people and a couple of trials of a treatment. “Never the same way twice” comes to mind.
Yet in large populations you can find general trends. Still, the “known sound treatment” may well kill some small fraction of the population and a drug that works fine in most will have unacceptable “side effects” in others. Why medicine is a “practice”…
So take all the below references and statements with a few tons of salt. It may well be an idiosyncratic thing in one person or one population, or just a statistical quirk. Yet some trends “fit”.
Vitamin D and Autism: A Case Report of Improved Symptoms
Chinese doctors report apparent response to vitamin D in toddler with autism and call for clinical trial to evaluate safety and benefits
December 15, 2014
Doctors in China are reporting that treatment with vitamin D appeared to produce dramatic improvements in a toddler with autism. They call on researchers to conduct clinical trials to evaluate the benefits and safety in individuals with autism and low vitamin D levels.
The report appears today in Pediatrics, the journal of the American Academy of Pediatrics.
“Scientists are studying the role of vitamin D in many brain disorders, from depression to dementia,” notes developmental pediatrician Paul Wang, Autism Speaks senior vice president for medical research. “This is an area where Autism Speaks is supporting research and is watching closely for results.”
That said, Dr. Wang cautions against reading too much into a single case report. “With one case report, it’s always possible that improvements in symptoms are coincidental or that the improvement is a matter of perception or placebo effect,” he says. “It’s also true that what seems to work for one child with autism may or may not work for other children.”
Full text of the original report PDF file here:
Core Symptoms of Autism Improved After Vitamin D Supplementation
Feiyong Jia, Bing Wang, Ling Shan, Zhida Xu, Wouter G. Staal, Lin Du
Autism spectrum disorder (ASD) is a common neurodevelopmental disorder caused by a complex interaction between genetic and environmental risk factors. Among the environmental factors, vitamin D3 (cholecaliferol) seems to play a significant role in the etiology of ASD because this vitamin is important for brain development. Lower concentrations of vitamin D3 may lead to increased brain size, altered brain shape, and enlarged ventricles, which have been observed in patients with ASD. Vitamin D3 is converted into 25-hydroxyvitamin D3 in the liver. Higher serum concentrations of this steroid may reduce the risk of autism. Importantly, children with ASD are at an increased risk of vitamin D deficiency, possibly due to environmental factors. It has also been suggested that vitamin D3 deficiency may cause ASD symptoms. Here, we report on a 32-month-old boy with ASD and vitamin D3 deficiency. His core symptoms of autism improved significantly after vitamin D3 supplementation. This case suggests that vitamin D3 may play an important role in the etiology of ASD, stressing the importance of clinical assessment of vitamin D3 deficiency and the need for vitamin D3 supplementation in case of deficiency.
Autism, or autism spectrum disorder (ASD), is a neurodevelopmental disorder, characterized by impairment in social interaction and communication, accompanied by stereotyped and repetitive behavior, with varied levels of severity.1–3 The genetic architecture of autism is complex, and its exact mechanisms remain elusive. Heritability estimates for ASD are about 50%.4,5 Most likely the risk of autism arises from sporadic DNA mutations. Environmental factors, such as higher age of the father or obesity, may be related to these mutations.6,7 Indeed, a growing body of literature suggests that certain modifiable risk factors such as maternal metabolic syndrome and certain vitamins such as vitamin D and folic acid either in utero or in early life may be associated with increased risk of autism.
Vitamin D deficiency may be one of the most important risk factors for several reasons. First, epidemiologic data on seasonal variation in birth rates and prevalence of autism suggest that maternal vitamin D deficiency is a risk factor for ASD. Second, reduced serum vitamin D levels have been associated with alexithymia, a condition that shows high comorbidity with autism. Third, there is reasonable theoretical support for a role of vitamin D in the etiology of ASD. Activated vitamin D upregulates the DNA repair gene, and vitamin deficiency during development may inhibit the repair of de novo DNA mutations during early fetal development. This would be in line with data from genetic studies showing an increased prevalence of rare mutations and copy number variation in autism. In addition, vitamin D may reduce the severity of autism through its antiinflammatory actions, increasing T-regulatory cells and antiautoimmune effects and upregulating glutathione, a scavenger of oxidative byproducts, thus contributing to a decreased risk of autism.
Here we present a case with ASD and vitamin D3 deficiency in whom supplementation of vitamin D3 had a marked effect on the core symptoms of autism.
Now consider that in the last few decades there has been a near paranoia about sun exposure with folks slathering their kids, and themselves, in all sorts of UV blockers before getting some sun…
Season with the reputation of ASD as “Geeks Disease” in Silicon Valley where there is the stereotype of a Geek at a computer terminal never seeing the sun… and where both Mom and Dad may well be indoors almost constantly, and dutifully keeping the kid out of the sun or covering them in sunscreen.
Now just where will they get their D3 from? Cod Liver Oil, while applied liberally by my Mum, is no longer in fashion.
When is their often “onset”? Just about the time a toddler is reducing milk intake and transitioning away from Vit D “enriched” milk and on to “solid foods” with typically little fish intake (so not much fish oil either).
Then what do we do with ‘wee ones’ who show ADSD symptoms? We tend to corral them inside “where they can’t get hurt” and certainly not let them run loose in the yard or bask in the sun… They also tend to very narrow diets that, I’d wager, do not tend to fish liver oil…
It just kind of fits.
Known risk factors
Risk factors for autism include:
Environmental toxins (exposure to chemicals and heavy metals), 
Genetic predisposition (children are at a 20% increased risk for ASD if their sibling is also affected),
Parents over the age of 35 years,
Taking certain medications that interfere with vitamin D metabolism during pregnancy, such as valproate, 
Complications during pregnancy and delivery.
There are numerous other risk factors, both genetic and environmental, but most researchers now believe there is an unidentified factor exists that interacts with both genes and the environment.  In his book, Dr. Cannell makes the case that vitamin D is that factor.
So who is most likely to be out at the beach or riding their bike: A 20 something new mom, or a 40 something late one?
Who is more likely to be outdoors jogging in the sun: A vital 20 something or a person with “metabolic disorder”?
The link between vitamin D and autism
In 2008, Dr. John Cannell of the Vitamin D Council published a paper on the link between autism and vitamin D.  This was the first published paper suggesting that vitamin D was associated with autism. The paper provided evidence for this relationship, such as an increased prevalence of autism in the USA in regions of greater cloud cover and rainfall. Also, in the United States, the rate of autism for children ages 6 to 17 years is highest in the regions of the country with the lowest solar UVB doses.  Whether this variation is due solely to vitamin D production or other factors of sunlight in addition to vitamin D production cannot be determined from this geographical ecological study.
Autism is also more common in areas with impaired UVB production, such as areas with high air pollution. Also, people who are dark skinned experience an increased risk for both vitamin D deficiency and autism.
A study conducted in the Faroe Islands found that those with ASD had lower vitamin D levels than their parents or siblings.  Most, but not all, studies have found children with ASD have lower levels of vitamin D than do typically developing controls.  According to several studies, more children with autism are born during the spring, which is the time of year with the lowest vitamin D levels in northern latitudes. 
In a groundbreaking discovery, researchers in Sweden have determined that children who later develop ASD had lower vitamin D levels at birth than their typically developing siblings do.  This helps rules out, but doesn’t entirely disprove, environmental factors as a cause of lower 25(OH)D levels in ASD children; it does suggest that heritability in vitamin D metabolism may cause the lower 25(OH)D levels at birth. Vitamin D levels at birth are dependent on the mother’s vitamin D levels, and one would think that a mother’s vitamin D levels would not drastically change from one pregnancy to the next. Therefore, this study suggests that the heritability of 25(OH)D, which ranges from 30% to 70% in different studies, is the genetic/environmental factor scientists have long sought in ASD.
Also, in another innovative study, Schmidt et al discovered that certain genes associated with lowered vitamin D blood levels are also associated with autism.  However, a Mendelian randomization study (where scientists study thousands of people for genetic defects in vitamin D metabolism to see if those genes are associated with autism) has not yet been done.
In the original, each of those references to a study is a link.
Maternal vitamin D deficiency and the risk of autism spectrum disorders: population-based study
Cecilia Magnusson, Michael Lundberg, Brian K. Lee, Dheeraj Rai, Håkan Karlsson, Renee Gardner, Kyriaki Kosidou, Stefan Arver, Christina Dalman
British Journal of Psychiatry Open Apr 2016, 2 (2) 170-172; DOI: 10.1192/bjpo.bp.116.002675
Background Maternal vitamin D deficiency may increase risk of autism spectrum disorder (ASD), but direct evidence is lacking.
Aims To clarify the relationship between maternal vitamin D deficiency and offspring risk of ASD with and without intellectual disability.
Method Using a register-based total population study (N=509 639), we calculated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of ASD with and without intellectual disability in relation to lifetime diagnoses of maternal vitamin D deficiency. Although rare, such deficiency was associated with offspring risk of ASD with, but not without, intellectual disability (aORs 2.51, 95% CI 1.22–5.16 and 1.28, 0.68–2.42). Relationships were stronger in non-immigrant children.
Conclusions If reflecting associations for prenatal hypovitaminosis, these findings imply gestational vitamin D substitution as a means of ASD prevention.
Declaration of interest None.
Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.
Autism spectrum disorders (ASDs) are developmental disorders associated with a high individual and societal burden, but their aetiology is poorly understood. Environmental and genetic factors appear equally important,1 although ASD with and without intellectual disability may in part have different origins.2,3
In high-latitude countries such as Sweden, children of mothers with dark complexion are at particularly elevated risk of ASD with intellectual disability.3 Because such women often have very low vitamin D levels due to melanin absorption of UVB radiation, maternal vitamin D deficiency has been suggested to contribute to ASD risk in offspring.4,5 Indeed, experimentally induced vitamin D deficiency in pregnant dams is reported to affect foetal neurodevelopment and behaviour in adult offspring in rats,4 and a recent study demonstrated lower neonatal vitamin D levels in children with ASD compared with their siblings.6
Early life vitamin D deficiency is thus a possible risk factor for ASD, but direct support of an association is lacking.4 Maternal hypovitaminosis D is treatable, thus investigation of the matter is warranted. We report here on the relationship between secondary care diagnosis of lifetime maternal vitamin D deficiency and offspring risk of ASD with and without intellectual disability, while addressing the influence of ethnicity. We use data from the Stockholm Youth Cohort (SYC), which allow for detailed case ascertainment in the total population of young people in Stockholm, Sweden.
The simple fact is that taking a vitamin supplement to raise your Vit D level is just not a very good way to do it. There are several different kinds of Vit D and what is in the bottle is often not ideal. Then there is the dose. Supplements often are in the low 100s of IU while a bit of sun time can create 10,000 scale IU (and of the right kind, that best used by mammals, too).
What has been one of THE biggest hallmarks of our last 1/2 century of “modernization”? People who never see the sun. We live inside a box, walk through the garage to our cars with UV blocking windows, drive to work and if we don’t park in an underground parking structure, make a quick dash to the entrance; then sit in a UV deprived environment until we drive home (often in the dark). Rinse and repeat. We expect the milk in our coffee to provide what is missing… /sarc;
I know my spouse and son both have mild SAD (Seasonal Affective Disorder) and we’ve bought UV lamps for each to assure that “stays away”. I try to “get some sun” whenever possible simply because I feel better then. I prefer places like California, Arizona, and Florida precisely because I can spend more time out in the sun. Pale skin, freckles and all.
Perhaps we have set the Vit D dietary requirements way too low for the modern life patterns. Perhaps especially so with the added metabolic and nutritional demands of pregnancy?
Maternal Vitamin D Levels May Prevent Autism In Kids
March 26, 2017 Author: Gaurav Shingala
Intake of Vitamin D supplements during the first trimester of pregnancy is likely to prevent the development of autism traits in children, researchers found in a study on mice.
Autism — or autism spectrum disorder — describes lifelong developmental disabilities including difficulty or inability to communicate with others and interact socially.
The discovery provides further evidence of the crucial role Vitamin D plays in brain development, said lead researcher Darryl Eyles, Professor at University of Queensland.
“We found that pregnant females treated with active vitamin D in the equivalent of the first trimester of pregnancy produced offspring that did not develop these deficits,” Eyles added.
Further, recent human studies also showed a link between pregnant women with low Vitamin D levels — also crucial for maintaining healthy bones — and the increased likelihood of having a child with autistic traits, the researchers said.
For the study, appearing in journal the Molecular Autism, the team used the most widely accepted developmental model of autism in which affected mice behave abnormally and show deficits in social interaction, basic learning and stereotyped behaviours.
The researchers also revealed that the active hormonal form of Vitamin D cannot be given to pregnant women because it may affect the skeleton of the developing foetus.
New studies are needed to determine how much cholecalciferol — the supplement form that is safe for pregnant women — is needed to achieve the same levels of active hormonal Vitamin D in the bloodstream, the researchers said.
Sun exposure is the major source of Vitamin D — which skin cells manufacture in response to ultraviolet rays — but it is also found in some foods such as in fatty fish like salmon and tuna, diary products, and cereals.
How about we just park “mum to be” in the sun for a while, eh?
Vitamin D treatment during pregnancy prevents autism-related phenotypes in a mouse model of maternal immune activation
Stephanie Vuillermot†, Wei Luan†, Urs Meyer and Darryl EylesEmail author
Molecular Autism: Brain, Cognition and Behavior 2017 8:9
© The Author(s). 2017 Received: 17 September 2016 Accepted: 21 February 2017
Published: 7 March 2017
Prenatal exposure to infection is a recognized environmental risk factor for neuropsychiatric disorders of developmental origins such as autism or schizophrenia. Experimental work in animals indicates that this link is mediated by maternal immune activation (MIA) involving interactions between cytokine-associated inflammatory events, oxidative stress, and other pathophysiological processes such as hypoferremia and zinc deficiency. Maternal administration of the viral mimic polyriboinosinic-polyribocytidylic acid (poly(I:C)) in mice produces several behavioral phenotypes in adult offspring of relevance to autism spectrum disorder (ASD) and other neurodevelopmental disorders.
Yet despite knowing that early infection exposure “causes issues” we insist on massive immune challenges to infants with multiple vaccinations at ever younger ages? Perhaps we ought to give the kids some time in the sun and / or test their Vit D levels (and the attendant reduction of inflammatory response) before we shoot them up with that much challenge? Maybe, just maybe, those “anecdotal” onset of ASD with immunizations is telling us which kids have a low vitamin D history and are especially susceptible to such challenge related damage? The interaction of a Vit D trigger and a challenge pull… IMHO, worth investigating. It would tend to explain the supposed mercury (heavy metals in general) link too. Neither one causal alone, but stimulative of the underlying issue in a select population.
Here, we investigated whether some of these phenotypes might also present in juveniles. In addition, given the known immunomodulatory and neuroprotective effects of vitamin D, we also investigated whether the co-administration of vitamin D could block MIA-induced ASD-related behaviors. We co-administered the hormonally active form of vitamin D, 1α,25 dihydroxy vitamin D3 (1,25OHD), simultaneously with poly(I:C) and examined (i) social interaction, stereotyped behavior, emotional learning and memory, and innate anxiety-like behavior in juveniles and (ii) the levels of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α in maternal plasma and fetal brains.
We show that like adult offspring that were exposed to MIA, juveniles display similar deficits in social approach behavior. Juvenile MIA offspring also show abnormal stereotyped digging and impaired acquisition and expression of tone-cued fear conditioning. Importantly, our study reveals that prenatal administration of 1,25OHD abolishes all these behavioral deficits in poly(I:C)-treated juveniles. However, prenatal administration of vitamin D had no effect on pro-inflammatory cytokine levels in dams or in fetal brains suggesting the anti-inflammatory actions of vitamin D are not the critical mechanism for its preventive actions in this ASD animal model.
This work raises the possibility that early dietary supplementation with vitamin D may open new avenues for a successful attenuation or even prevention of neurodevelopmental disorders following maternal inflammation during pregnancy.
Epidemiologic evidence supporting the role of maternal vitamin D deficiency as a risk factor for the development of infantile autism.
Grant WB, Soles CM.
This study examines whether maternal vitamin D deficiency is a risk factor for infantile autism disease (IAD). We used epidemiologic data seasonal variation of birth rates and prevalence of IAD for cohorts born before 1985. For seven studies reporting spring-to-summer excess birth rates for IAD, the season progressed from broad near 30 degrees N latitude, spring/summer in midlatitudes, to winter at the highest latitude. Also, using data from 10 studies, we found a strong effective latitudinal (related to wintertime solar ultraviolet B radiation) increase in IAD prevalence. These findings are consistent with maternal vitamin D deficiency’s being a risk factor for IAD, possibly by affecting fetal brain development as well as possibly by affecting maternal immune system status during pregnancy. Further investigation of this hypothesis is warranted.
It sure looks like a fair amount of evidence is stacking up. So if you know a “mom in the making”, perhaps having some beach time, pool time, or just a walk in the sun would be A Good Thing. At least get a Vit D test done to determine if levels are normal.
I don’t think I’d go so far as to buy a “Lizard Lamp” (they need UV too…) unless advised to up your game by an M.D. ;-) but certainly don’t avoid the sun and especially in winter or up north don’t slather on gobs of sunscreen every time you step outside…
Oh, and maybe develop a fondness for “Fish and Chips” ( I doubt anyone can develop a fondness for Cod Liver Oil, though I did like the C.L.O. pills my Mum fed me… )
For my money, the variation with season, with melanin levels of population at high latitude, and the mouse direct response are pretty strong evidence of some kind of solar / Vit D level impact.
Well, I think I’m going to take my mid morning tea out on the patio in the sun… That suppression of inflammatory response sounds good to these old joints ;-)