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On the aetiology of autism

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  • Vitamin D Council, Inc.
A DIFFERENT VIEW
On the aetiology of autism
John J Cannell (jcannell@ash.dmh.ca.gov; jjcannell@vitamindcouncil.org)
Atascadero State Hospital – Psychiatry, Atascadero, CA, USA
Correspondence
John J Cannell, Atascadero State Hospital – Psychia-
try, 10333 El Camino Real, Atascadero, CA 93423,
USA.
Tel: +805 468 2061 |
Fax: +805 439 1073 |
Email: jcannell@ash.dmh.ca.gov;
jjcannell@vitamindcouncil.org
Received
26 March 2010; accepted 10 May 2010.
DOI:10.1111/j.1651-2227.2010.01883.x
Re-use of this article is permitted in accordance with
the Terms and Conditions set out at http://www3.
interscience.wiley.com/authorresources/
onlineopen.html.
I have suggested that the primary environmental trigger for
autism is not vaccinations, toxins or infections, but
gestational and early childhood vitamin D deficiency (1,2).
Subsequently, the title of an article in Scientific American
recently asked, ‘What if vitamin D deficiency is a cause of
autism?’ (3) Since then, an article on vitamin D and autism
in Acta Paediatrica (4) and the accompanying commentary
(5) have added to the accelerating suspicion that vitamin D
deficiency – either during pregnancy or early childhood –
may be an environmental trigger for the genetic disease of
autism.
I will not repeat the evidence from my original 2007
paper and I am well aware that evidence consistent with a
theory is not proof of that theory. Instead, I concentrate on
papers either published since my paper, or on evidence I
overlooked when researching the original paper. Finally, I
explain my reasons why this theory deserves immediate
attempts to disprove it.
Simultaneous with the above two Acta Paediatrica publi-
cations, a paper elsewhere reported that among 117 adult
psychiatric outpatients is Sweden with various diagnoses,
the 10 patients with autism had the lowest vitamin D levels
of any of the groups studied, a mean of 12 ng mL (31 nM),
approaching the osteomalacic range for adults and the
rachitic range for children (6). Even more interesting, some
of the patients seemed to improve when treated with an
average dose of about 4000 IU of vitamin D day. The
authors did not say if the improvement occurred in the aut-
ism group.
A 2008 review detailed the devastating effect gestational
vitamin D deficiency has on developing mammalian brains
(7). Unfortunately, the tiny 10 lg (400 IU) dose in prenatal
vitamins is virtually irrelevant in preventing the current epi-
demic of gestational vitamin D deficiency (8). For this rea-
son, in 2007, the Canadian Paediatric Society cautioned
pregnant women they may require not 400 IU day but
2000 IU day, or more, to prevent gestational vitamin D
deficiency (9).
If adequate amounts of vitamin D prevent autism, one
would expect children with rickets to have an increased risk
of autism. To my knowledge, the neuropsychiatric symp-
toms of rickets have not been studied in the modern era.
However, at least two old papers have addressed it (10,11),
both published before Kanner described autism in 1943.
Both papers describe ‘weak mindedness,’ ‘feeble minds,’
‘mental dullness,’ unresponsiveness and developmental
delays. Even more intriguing, both papers report that the
mental condition in rickets improved with vitamin D.
Another of the mysteries of autism is the apparent
increased incidence of autism in the children of richer col-
lege-educated parents, especially women, a finding
announced a few months ago (12). Actually, this is not a
new finding. As I discussed in my original paper, this has
been known since the early 1980s but was dismissed as
being because of ascertainment bias. This very recent report
correlates well with a 2007 CDC report (13), which found a
similar increased risk for the wealthy and well-educated,
Articles in the series A Different View are edited by Alan Leviton
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Acta Pædiatrica ISSN 0803–5253
ª2010 The Author/Journal Compilation ª2010 Foundation Acta Pædiatrica/Acta Pædiatrica 1
findings the authors tried but could not dismiss as being
because of ascertainment bias. If the vitamin D theory is
true, autism should be more common in richer well-edu-
cated mothers, who are more likely than other mothers to
practice sun avoidance and use sunblock (1,2).
In his invited commentary, Dr. Eyles asked, ‘Does skin
colour modify the risk’ of autism, noting melanin in the skin
is an effective sunblock. Such studies are difficult as they
raise sensitive social issues. Nevertheless, three of four
recent U.S. studies found a higher incidence of autism in
black children, sometimes appreciably higher (1,2). As
Fernell et al. report, the Somali immigrants in Sweden call
autism the ‘Swedish disease’ and Somali immigrants in Min-
nesota call it the ‘American disease,’ but in equatorial
Somalia, autism has no name.
Toxins delivered by water or air pollution appear to dam-
age the genome of the vitamin D deficient (14). If exposure
to such toxins were the main contributors to autism inci-
dence, then we should have seen an autism incidence pat-
tern in the US that mirrored air and water pollution with a
dramatic increase in the 1950s, a peak in the 1960s and then
a progressive decline by the early 1980s, coincident with
enactment and enforcement of the US clean air and clean
water acts of the 1960s.
Another possibility is that air pollution from Eastern Eur-
ope, India and China, which has been increasing in the last
20 years, has engendered the current crop of autism. How-
ever, why would foreign air pollution of today do what
American air pollution of the 1950s and 60s could not?
Another paper published after my original paper found
that autistic boys have unexplained reductions in metacar-
pal bone thickness (15). At some time in their life, these
children laid down less cortical bone than normal children,
a finding consistent with undetected and untreated child-
hood or even intrauterine vitamin D deficiency.
Yet another recent paper reported that the prevalence of
autism in three U.S. states was higher in areas of higher
precipitation and clouds (16). The 2005 autism prevalence
rate among school-aged children, after controlling for dif-
ferences in population size, demographic characteristics,
per capita income and state, was higher in cloudy areas.
The association of autism prevalence and the mean annual
precipitation received by a county between 1987 and 2001
was positive and significant (p = 0.0034; 95% confidence
interval, 0.0018–0.0050). Clouds and rain retard vitamin
D-producing ultraviolet B light from penetrating the atmo-
sphere.
Surprisingly, high maternal seafood consumption, of the
type known to be contaminated with mercury, has been
associated with fewer – not more – autistic markers in the
offspring (17). Lower maternal seafood intake during preg-
nancy was associated with low verbal intelligence quotient,
suboptimum outcomes for prosocial behaviour, fine motor,
communication and social development scores. While the
omega-3 and mercury content of fish is well known, less
well known is the fact that fish is one of the few foods with
significant amounts of vitamin D, which, as referenced
earlier, protects the genome from damage by toxins.
While the urban rural gradient in rickets is well known
and was one of the keys to discovering that sunlight pre-
vented rickets, less well known is a meta-analysis showing a
twofold urban rural gradient for autism (18). Similar to
rickets, city life affords less vitamin D, because of tall build-
ings, indoor occupations and increased urban air pollution,
all of which block ultraviolet B light from penetrating the
atmosphere.
Finally, a 2008 paper reported that autism was more com-
mon among mothers who took antiepileptic drugs (19). A
comment to the authors (20) detailed the evidence that an-
tiepileptic drugs are one of the few classes of drugs that con-
sistently and significantly interfere with vitamin D
metabolism, lowering 25(OH)D levels.
I agree with Dr Eyles’ comment that the vitamin D the-
ory is ‘highly parsimonious.’ Indeed, it was love of
parsimony that led me to first hypothesize that vitamin D is
intimately involved in the pathology and epidemiology of
both autism and influenza (21). Some have speculated that
the excess of winter births in autism is explained by
wintertime maternal viral infections. Obviously, another,
and more parsimonious explanation, is that vitamin D is
involved in all three.
The vitamin D theory of autism does not diminish genetic
contributions to autism occurrence. Indeed, without the
genetic tendency for autism, I suspect that severe maternal
or early childhood vitamin D deficiency may cause bone
abnormalities, as referenced above, with no evidence aut-
ism. All that the current epidemic of maternal and early
childhood vitamin D deficiency does, with its resultant neu-
ral deficiency in the pluripotent neurosteroid calcitriol, is to
allow the genetic tendency for autism to express itself.
If this theory is true, the path towards effective preven-
tion – and perhaps a treatment effect if adequate physio-
logical doses of vitamin D are given – is so simple, so safe,
so inexpensive, so readily available and so easy, that it
defies imagination. Seventeen vitamin D experts recently
stated, ‘In our opinion, children with chronic illnesses such
as autism, diabetes and or frequent infections should be
supplemented with higher doses of sunshine or vitamin
D3, doses adequate to maintain their 25(OH)D levels in
the mid-normal of the reference range [65 ng mL
(162 nmol L)] – and should be so supplemented year
round.’ (22)
Finally, if true, a darker side of the theory emerges. To
some real but unknown extent, autism is an iatrogenic dis-
ease, caused by governments, organizations, committees,
newspapers and physicians who promulgated the current
warnings about sun-exposure for pregnant women and
young children without any understanding of the tragedy
they engendered.
DISCLAIMER
Dr Cannell is founder and executive director of the non-
profit educational organization, the Vitamin D Council. He
also receives remuneration from Purity Products, a supple-
ment manufacturer.
Aetiology of autism Cannell
2ª2010 The Author/Journal Compilation ª2010 Foundation Acta Pædiatrica/Acta Pædiatrica
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Cannell Aetiology of autism
ª2010 The Author/Journal Compilation ª2010 Foundation Acta Pædiatrica/Acta Pædiatrica 3
... Autism spectrum disorder (ASD), a brain developmental turmoil with a predestined 2 % prevalence. In recent years, has become increasingly prevalent the pathogenesis has a negative effect on children's lives through social behavioral and emotional (1) . In etiology, genetic, neurobiological, idiopathic, immunological and postnatal agents may play a significant role (2) . ...
... while the genotype TT showed a significant (p=0.00) higher frequencies within control group compared to patients (50% and 26%, respectively) with preventive fraction equal to 0.35, as seen in table (1). ...
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Autism Spectrum Disorder (ASD) is a developmental disorder that affects actions and connection. While autism can be diagnosed at any age, it is considered to be a " developmental disorder" because symptoms usually occur in the first two years of life. A total of fifty patients with Autism spectrum disorder (ASD) and fifty control groups were enrolled in this study, age range of 2-14 years old. The study was conducted between August 2019 and January 2020 samples were collected from Al-Noor Autism Institute and the Central Teaching Hospital of pediatric .The Vitamin D receptor was measured by ELISA and Vitamin D was measured by AFIAS-6 Compact Desktop Immuno-analyzer. Genotyping was performed using the TaqMan SNP genotyping assay using Real-Time PCR system. The results of this study revealed that vitamin D and Vitamin D receptor were significantly high in control group than in patients group, while were significantly higher in MDA (µmol/I) levels in patients group than those of control group, and the results of the genotyping showed genotype TT significantly higher in patients than in control group with etiological factor equal to 6.9.
... Autism spectrum disorder (ASD), a brain developmental turmoil with a predestined 2 % prevalence. In recent years, has become increasingly prevalent the pathogenesis has a negative effect on children's lives through social behavioral and emotional (1) . In etiology, genetic, neurobiological, idiopathic, immunological and postnatal agents may play a significant role (2) . ...
... while the genotype TT showed a significant (p=0.00) higher frequencies within control group compared to patients (50% and 26%, respectively) with preventive fraction equal to 0.35, as seen in table (1). ...
Article
Autism Spectrum Disorder (ASD) is a developmental disorder that affects actions and connection. While autism can be diagnosed at any age, it is considered to be a " developmental disorder" because symptoms usually occur in the first two years of life. A total of fifty patients with Autism spectrum disorder (ASD) and fifty control groups were enrolled in this study, age range of 2-14 years old. The study was conducted between August 2019 and January 2020 samples were collected from Al-Noor Autism Institute and the Central Teaching Hospital of pediatric .The Vitamin D receptor was measured by ELISA and Vitamin D was measured by AFIAS-6 Compact Desktop Immuno-analyzer. Genotyping was performed using the TaqMan SNP genotyping assay using Real-Time PCR system. The results of this study revealed that vitamin D and Vitamin D receptor were significantly high in control group than in patients group, while were significantly higher in MDA (µmol/I) levels in patients group than those of control group, and the results of the genotyping showed genotype TT significantly higher in patients than in control group with etiological factor equal to 6.9.
... Autism spectrum disorder (ASD), a brain developmental turmoil with a predestined 2 % prevalence. In recent years, has become increasingly prevalent the pathogenesis has a negative effect on children's lives through social behavioral and emotional (1) . In etiology, genetic, neurobiological, idiopathic, immunological and postnatal agents may play a significant role (2) . ...
... while the genotype TT showed a significant (p=0.00) higher frequencies within control group compared to patients (50% and 26%, respectively) with preventive fraction equal to 0.35, as seen in table (1). ...
... The potential impact of vitamin D on ASD onset has been discussed extensively during the last two decades [12,57,58]. Connection between vitamin D and ASD onset give facts that individuals with ASD have been observed to suffer from vitamin D deficiencies [59][60][61][62], and vitamin D supplementation may improve their socio-psychological status [63,64]. ...
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... Several biological abnormalities have been found to be associated with autism, including early brain enlargement (Courchesne & Pierce, 2005), reduced brain interconnectivity (Just, Cherkassy, Keller, & Minshew, 2004), a defective mirror neuron system (Martineau, Cochin, Magne, & Barthelemey, 2008), vitamin D deficiency (Cannell, 2010), and reduced levels of the neuropeptide Oxytocin (Green et al., 2001). However, none of these biological 'markers' can be found in the large majority of individuals diagnosed with autism, and many of the proposed abnormalities also tend to be associated with a range of other neurodevelopmental conditions (Walsh, Elsabbagh, Bolton, & Singh, 2011). ...
Thesis
This paper describes a qualitative study designed to explore the lived experiences of children diagnosed with Autism Spectrum Disorder (ASD). The voices of these children have often been missing in bioethical arguments about potential threats of psychiatric diagnosis and treatment to children’s sense of identity and moral self-understanding. This study aimed to examine the suitability of activity-based interviews to elicit these children’s perspectives, and to empirically evaluate the social and moral dimensions of an ASD diagnosis. Participants included six children diagnosed with ASD ranging in age from 8 to 14. Methods used include photo elicitation, drawing, sentence starters, and the making of a collage. Through thematic analysis, four main themes were identified: anger and losing control of the self; brain, power, and responsibility; identity and authenticity; and friendship, bullying, and stigma. The use of multiple qualitative strategies proved to be valuable in engaging children in the study and eliciting their perspectives. Children’s self-understandings appear to be structured by their ASD diagnosis and treatment; however, these effects are in part positive. Nonetheless, children also describe frequently encountering stigma and bullying about their diagnosis. Implications of these results and suggestions for further research are discussed.
... A numbers factor such as genetic, neurobiological, idiopathic, immunologic, environmental, prenatal, natal, and postnatal may have an important role in the etiology. 1,2) Numerous reports have described the etiology of ASD. In recent years, there has been a rapid increase in studies of vitamin D as an environmental factor in many medical diseases. ...
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... Доведений зв'язок між наявністю поліморфізмів гену VDR та розладами аутичного спектру [33]. Крім того, в останній час приділяється увага стану метилювання гену CYP2R1при недостатності вітаміну D в організмі. ...
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Prenatal environmental exposures are among the risk factors being explored for associations with autism. We applied a new procedure combining multiple scan cluster detection tests to identify geographically defined areas of increased autism incidence. This procedure can serve as a first hypothesis-generating step aimed at localized environmental exposures, but would not be useful for assessing widely distributed exposures, such as household products, nor for exposures from nonpoint sources, such as traffic. Geocoded mothers' residences on 2,453,717 California birth records, 1996–2000, were analyzed including 9,900 autism cases recorded in the California Department of Developmental Services (DDS) database through February 2006 which were matched to their corresponding birth records. We analyzed each of the 21 DDS Regional Center (RC) catchment areas separately because of the wide variation in diagnostic practices. Ten clusters of increased autism risk were identified in eight RC regions, and one Potential Cluster in each of two other RC regions. After determination of clusters, multiple mixed Poisson regression models were fit to assess differences in known demographic autism risk factors between the births within and outside areas of elevated autism incidence, independent of case status. Adjusted for other covariates, the majority of areas of autism clustering were characterized by high parental education, e.g. relative risks >4 for college-graduate vs. nonhigh-school graduate parents. This geographic association possibly occurs because RCs do not actively conduct case finding and parents with lower education are, for various reasons, less likely to successfully seek services.
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Optimal neurodevelopment of the fetus depends in part on an adequate supply of docosahexaenoic acid (DHA), an omega-3 essential fatty acid that is abundant in seafood. A diet lacking in seafood could impair development because of too little long-chain omega-3 fatty acids such as DHA and eicosapentaenoic acid. Nevertheless, federal agencies have recommended limiting seafood consumption by parturients to 340 g per week so as to avoid exposing the fetus to trace amounts of neurotoxins. The investigators used data from the Avon Longitudinal Study of Parents and Children to clarify the influence of maternal seafood intake during pregnancy on developmental, behavioral, and cognitive outcomes at ages 6 months to 8 years. Participating were 11,875 pregnant women who completed a food frequency questionnaire at 32 weeks’ gestation. Children were assessed using items from the Denver Developmental Screening Test as well as the Strengths and Difficulties Questionnaire and verbal and performance intelligence quotient (IQ) scores. About one-third of women in the study ate up to 340 g of seafood each week, whereas 12% ate no seafood at all while pregnant. Just under one-fourth of women ate more than 340 g weekly. Low seafood consumption correlated with a socially disadvantageous setting including low educational levels and also with less than ideal lifestyles. After adjusting for these and other variables, eating less than 340 g of seafood each week correlated with an increased likelihood of a verbal IQ in the lowest quartile. The odds ratio (OR) for women eating no seafood, compared with those eating more than 340 g weekly, was 1.48 with a 95% confidence interval (CI) of 1.16–1.90. For women eating some seafood but less than 340 per week the OR for low verbal intelligence was 1.09 (95% CI, 0.92–1.29). Low seafood intake also was associated with suboptimal outcomes for prosocial behavior, fine motor function, communicative ability, and social development scores. In each instance, the risk of a suboptimal outcome increased with declining levels of seafood intake. Fewer than 2% of women in this study consumed fish oil supplements while pregnant. Outcomes of infants whose mothers took a supplement but did not eat seafood were similar to those in infants whose mothers did eat seafood. No trend toward benefit in any neurodevelopmental domain was observed when the weekly seafood intake was less than 340 g. These findings suggest that limiting weekly seafood consumption to less than 340 g may have adverse effects on early childhood neurodevelopment. The authors believe that a lack of essential nutrients is more harmful than potential exposure to the trace contaminants present in some seafood.
Article
Unlabelled: Any theory of autism's etiology must take into account its strong genetic basis while explaining its striking epidemiology. The apparent increase in the prevalence of autism over the last 20 years corresponds with increasing medical advice to avoid the sun, advice that has probably lowered vitamin D levels and would theoretically greatly lower activated vitamin D (calcitriol) levels in developing brains. Animal data has repeatedly shown that severe vitamin D deficiency during gestation dysregulates dozens of proteins involved in brain development and leads to rat pups with increased brain size and enlarged ventricles, abnormalities similar to those found in autistic children. Children with the Williams Syndrome, who can have greatly elevated calcitriol levels in early infancy, usually have phenotypes that are the opposite of autism. Children with vitamin D deficient rickets have several autistic markers that apparently disappear with high-dose vitamin D treatment. Estrogen and testosterone have very different effects on calcitriol's metabolism, differences that may explain the striking male/female sex ratios in autism. Calcitriol down-regulates production of inflammatory cytokines in the brain, cytokines that have been associated with autism. Consumption of vitamin D containing fish during pregnancy reduces autistic symptoms in offspring. Autism is more common in areas of impaired UVB penetration such as poleward latitudes, urban areas, areas with high air pollution, and areas of high precipitation. Autism is more common in dark-skinned persons and severe maternal vitamin D deficiency is exceptionally common the dark-skinned. Conclusion: simple Gaussian distributions of the enzyme that activates neural calcitriol combined with widespread gestational and/or early childhood vitamin D deficiency may explain both the genetics and epidemiology of autism. If so, much of the disease is iatrogenic, brought on by medical advice to avoid the sun. Several types of studies could easily test the theory.
Article
To analyse serum levels of 25-hydroxyvitamin D in mothers of Somali origin and those of Swedish origin who have children with and without autism as there is a growing evidence that low vitamin D impacts adversely on brain development. Four groups of mothers were invited to participate; 20 with Somali origin with at least one child with autism, 20 with Somali origin without a child with autism, 20 of Swedish origin with at least one child with autism and 20 with Swedish origin without a child with autism. Two blood samples were collected from each individual; during autumn and spring. Between 12 and 17 mothers from the different groups accepted to participate, both groups of mothers of Somali origin had significantly lower values of 25-hydroxyvitamin D compared with Swedish mothers. The difference of 25-hydroxyvitamin D between mothers of Somali origin with and without a child with autism was not significant. Our findings of low vitamin D levels in Somali women entail considerable consequences in a public health perspective. The observed tendency, i.e. the lowest values in mothers of Somali origin with a child with autism was in the predicted direction, supporting the need for further research of vitamin D levels in larger samples of Somali mothers of children with and without autism.
Article
In a chart review at a psychiatric out-patient department, latitude 59.3 degrees N, a sample of patients with tests of serum 25-hydroxy-vitamin D (25-OHD) and plasma intact parathyroid hormone (iPTH) was collected, together with demographic data and psychiatric diagnoses. During 19 months, 117 patients were included. Their median 25-OHD was 45 nmol/l; considerably lower than published reports on Swedish healthy populations. Only 14.5% had recommended levels (over 75). In 56.4%, 25-OHD was under 50 nmol/l, which is related to several unfavourable health outcomes. Seasonal variation of 25-OHD was blunted. Patients with ADHD had unexpectedly low iPTH levels. Middle East, South-East Asian or African ethnic origin, being a young male and having a diagnosis of autism spectrum disorder or schizophrenia predicted low 25-OHD levels. Hence, the diagnoses that have been hypothetically linked to developmental (prenatal) vitamin D deficiency, schizophrenia and autism, had the lowest 25-OHD levels in this adult sample, supporting the notion that vitamin D deficiency may not only be a predisposing developmental factor but also relate to the adult patients' psychiatric state. This is further supported by the considerable psychiatric improvement that coincided with vitamin D treatment in some of the patients whose deficiency was treated.