This is an evolving topic. Maternal antibodies to fetal brain have been associated with autism in a number of studies. Prenatal stressors appear to also be related. Recent studies have also suggested some types of toxic exposures are also related, for example, an increased incidence of autism is observed in families living near Interstate highways. General maternal immune response also appears to have some relationship. Maternal inflammation could concievably be a common mechanism for a number of these, particuarly stressors, but our understanding is still early in development. I know of no evidence that maternal inflammation has increased overall in the general population, although it is concievable that is so given many changes in our society (dietary, evironmental, etc). It must be noted that there is debate regarding how much of the reported increase in autism is related to increased recognition and diagnosis.

There is no convincing evidence that autism is linked to risk factors such as maternal inflammation, infection, diabetes, and toxicant exposures. Some years ago, we provided the attached study regarding the sulphation deficit in low-functioning autistic children. All that contributes to this deficit can, of course, be a risk factor for these patients

Article Sulphation deficit in "Low-Functioning" autistic children: A...

Could maternal inflammation be a common mechanism connecting environmental risk factors to autism?

From what we know about the inheritance of autism we can say that the answer for this question is no. If maternal inflammation was an important factor we would expect to see similar rates of autism in fraternal and identical twins, but we see a big difference. The evidence relating the factors you mentioned specifically to autism are weak.

Risk factors for autism supported by solid evidence are rare genetic events and father's age. From the genetics we know that many different mutations are implicated in autism. Therefore I would not expect to find a common environmental factor leading to autism but many different factors that interact with the different mutations.

These other issues are an evolving literature, without firm evidence. For maternal antibodies, though, there is substantial literature

Zimmerman AW, Connors SL, Matteson KJ, et al. Maternal antibrain antibodies in autism. Brain Behav

Immun 2007;21:351-7.

Martin LA, Ashwood P, Braunschweig D, Cabanlit M, Van de Water J, Amaral DG. Stereotypies and

hyperactivity in rhesus monkeys exposed to IgG from mothers of children with autism. Brain Behav Immun

2008.

Martin, L. A. , Ashwood, P. , Braunschweig, D. , Cabanlit, M.. Van de Water, J., and D. G. Amaral, An

immunological model of autism in the nonhuman primate. Brain Behavior and Immunity, E-Pub Feb 7,

2008.

Braunschweig D, Ashwood P, Hertz-Picciotto I, et al. Maternal serum antibodies to fetal brain in autism.

Neruotoxicology 2008;29:226-31.

Dalton P, Deacon R, Blamire A, et al. Maternal neuronal antibodies associated with autism and a

language disorder. Ann Neurol 2003;53(4):533-7.

Singer HS, Morris CM, Gause CD, Gillin PK, Crawford S, Zimmerman AW. Antibodies against fetal

brain in sera of mothers with autistic children. J Neuroimmunol 2008;194(1-2):165-72.

Croen LA, Braunschweig D, Haapanen L, et al. Maternal Mid-Pregnancy Autoantibodies to Fetal Brain

Protein: The Early Markers for Autism Study. Biol Psychiatry 2008.

Wills, S. Cabanlit, M., Bennett, J., Ashwood, P., Amaral, D.G., and Van de Water, J. Detection of

autoantibodies to neural cells of the cerebellum in the plasma of subjects with autism spectrum disorders.

Brain Behavior and Immunity 23: 64-74, 2008.

Cabanlit, M., Wills, S. Goines, P., Ashwood, P and Van de Water, J. Brain-specific Autoantibodies in the

plasma of subjects with autistic spectrum disorder. Ann. N.Y. Acad. Sci, 1107:92-103, 2007.

This is an interesting question that has been receiving considerable attention of late. The maternal infection animal model has is roots in epidemiology -- women with second trimester infections are at greater risk for having children with autism (and schizophrenia). Several recent studies have also linked maternal autoimmune dysfunction with greater autism risk. Hypothesized links between the rise in childhood asthma and autism have new data to lend credence to this perspective, including a 2013 study of perinatal pollutant exposure (http://ehp.niehs.nih.gov/wp-content/uploads/121/6/ehp.1206187.pdf). Finally, it is worth noting that although autism is diagnosed as if it is a unitary phenomenon, albeit along a spectrum, it is probably more correct to think of multiple physiological mechanisms with a common behavioral presentation. It is possible that there is an inflammation-related subtype. Indeed, David Amaral, Judy Van de Water and colleagues at UC Davis are exploring this.

" It seems that the autist brain is wired differently as compared normal individuals"

Yes, but this gets us nowhere since this could be the result of autistic symptoms just as much as the cause. Also, the earliest brain abnormality in those at high risk for autism is in CSF volume not brain tissue (as also in schizophrenia).

On environmental factors, I suggest reviewing the CHARGE studies from UC Davis. There are some things that do surface in epidemiological studies.

I was surprised to see the responses from Guy Horev and Corrado Romano. I though that it was clear that the maternal environment is an important factor in the etiology of autism. I think that the evidence linking maternal environmental factors to autism is convincing, so I thought I should provide some citations to discuss.

Guy, I agree that their must be a genetic component to explain elevated incidence among identical twins compared to fraternal twins. However, I disagree with your argument that a significant environmental influence would result in the same incidence among fraternal and identical twins. Clearly gene-environment interactions are possible. Considering the fact that twins have a higher concordance rate of autism compared to siblings; I think an environmental influence is likely.

Genetic heritability and shared environmental factors among twin pairs with autism.

PMID: 21727249

Specifically, there is evidence for an association between maternal diabetes and the incidence of autism.

Maternal Diabetes and the Risk of Autism Spectrum Disorders in the Offspring: A Systematic Review and Meta-Analysis.

PMID: 24057131

Developmental toxicant exposures are associated with autism incidence and the example of fetal valproate exposure has even been developed as an animal model to study autism.

Fetal valproate syndrome and autism: additional evidence of an association.

PMID: 11263692

Autism spectrum disorders following in utero exposure to antiepileptic drugs.

PMID: 11263692

The critical period of valproate exposure to induce autistic symptoms in Sprague-Dawley rats.

PMID: 21195144

Furthermore, prenatal multi-nutrient supplement use is associated with reduced risk of autism.

Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study.

PMID: 2022648721

Have you considered alcohol as a developmental teratogen? I a attaching a chapter from Irish psychiatrist, Dr Kieran O'Malley, who is an expert of fetal alcohol spectrum disorders (FASD). Do all clinicians ask about maternal alcohol use during the pregnancy?

"However, I disagree with your argument that a significant environmental influence would result in the same incidence among fraternal and identical twins. Clearly gene-environment interactions are possible"

When I looked some time ago at the New York twin study from about 50y ago, I was struck by the observation, admittedly on small numbers, that there was a higher MZ concordance for environmental triggers of deafness, infections etc, than for genetic factors alone. I have also wondered with congenital infections like rubella if there was greater MZ than DZ concordance despite a common uterine environment, but I don't think I ever found enough data to check this. There can be an inverse relation between autism and deafness. Many rubella infants start off as autistic, but as the cochlea is progressively destroyed they then manifest as conventional congenitally deaf.

"I though that it was clear that the maternal environment is an important factor in the etiology of autism"

So someone needs to show that there is lower heritability for autism when due to supposed maternal causes.

Read my answer again, I did not say there is no environmental influence, I said that it is unlikely to find a common environmental factor causing autism. Based on estimates that 500-1000 genes are implicated in autism, I expect that different environmental factors will interact with different genes.

Johnathan, regarding some references you mentioned:

The first reference you mentioned (twin study) does not have sibling data, only twins. Their data is very similar to earlier studies that suggest 90% heritability. In this paper they suggest a different model, at this stage it is hard to say if their model is better.

The maternal diabetes study found a small but significant elevation in autism rates in diabetic mothers, meaning that most mothers with maternal diabetes won't have autistic child, and some mothers without maternal diabetes will have autistic child. So maternal diabetes is not a common risk for autism. It is possible to suggest the following genetic explanation for their findings. Some mothers carry allele that increase risks for both maternal diabetes and ASD, since ASD has gender bias the mothers are immune to ASD but if their male offspring inherit the allele he is at high risk for ASD.

Exposure to antiepileptic drugs again may be explained in the same way, note that if the mother takes antiepileptic drugs in her pregnancy she probably has severe epilepsy, and epilepsy rates within autistic people are higher than within the general population.

Hello Guy,

I appreciate your thoughtful comments.

It looks like sibling concordance is around 3% (PMID: 6456787) which is around an order of magnitude less than DZ concordance.

I agree that the association between maternal diabetes and autism is small. I am not asking if maternal diabetes is the ultimate cause of all cases of autism. I am more interested in the idea that maternal inflammation is a common risk factor that interacts with genetic susceptibility factors to cause autism. Maternal diabetes is one example of a condition associated with inflammation that increases risk of autism. Maternal infection is another. I think intoxication (eg. ethanol, valproic acid, thalidomide, mercury, lead, and car exhaust) and malnutrition could also contribute to maternal inflammation. Do you think maternal inflammation is an important factor?

Hi Jonathan,

I worked on the maternal inflammation - autism link as a grad student in Paul Patterson's lab. We found that cytokines- IL6 in particular- can alter the brain development of mice, and their behavior as adults. There are quite a few studies out there now backing this up, and some evidence that the brains and immune systems of of these mice also show long-term alterations.

I now work in an immunology department, and people are always talking about how the incidence of autoimmune disease is on the rise- asthma is a good example. Obesity, also obviously on the rise, is also associated with inflammation, as are many common environmental contaminants. So, yes, I really like the idea that maternal inflammation could link increased autism rates with observations from other fields. As for hard data on a general increase in inflammation during pregnancy, though, I haven't heard of any. That would be a tough study to do.

Hi Johnathan,

It is impossible to compare the two studies, the sibling study performed in 1981 the twin study performed in 2011. There are some reports that compared autism rate between dizygotic twins, and non-twin siblings, in the same study, none of them reported an order of magnitude difference, see this review (PMID:15121991) for example.

I am not familiar with the literature about maternal inflammation, I think that a good starting point for maternal effects will be high-risk pregnancies, in particular premature births.

I have just come across a paper (Med Times Gaz 1866;1:412) on a family with Usher syndrome, a genetic disorder leading to blindess, deafness and autism, which indicates gene-environment interaction, as mentioned previously. Five sibs had visual and auditory problems, five not, consistent with a recessive gene. However, the manifestation of deafness differed widely: sib 1 - deaf in childhood, now improving; sib 2 - hearing more impaired, but not seriously; sib 3 - much more deaf; sibs 4 and 5 - extremely deaf. The defects were first noticed in all the cases at periods of dentition. It is of course easy to dismiss these parental observations, but from my notes I see that in Acta Psych Scand 1959 Supp 138, parents said that the Usher deafness started with infection in infancy, which of course the doctors denied, saying instead it was genetic!

Hi Steven, interesting point,

"Obesity, also obviously on the rise, is also associated with inflammation, as are many common environmental contaminants. So, yes, I really like the idea that maternal inflammation could link increased autism rates with observations from other fields."

A recent study in Pediatrics found "diabetes, hypertension, and obesity were more common among mothers of children with ASD and DD compared with controls."

Metabolic syndrome (diabetes, hypertension, and obesity) involves chronic inflammation. This supports your hypothesis that increased IL-6 signaling (eg. resulting from maternal metabolic syndrome) could be a mechanism that disrupts fetal brain development contributing to autism.

http://pediatrics.aappublications.org/content/129/5/e1121.short

In my opinion dietary factors may play an indirect role in autism. I have introduced a new disease model called Carbohydrate Associated Reversible Brain syndrome or CARB syndrome. CARB syndrome is a form of food-induced brain dysfunction triggered by long-term exposure to processed food.

Many people with autism also have CARB syndrome. Because the symptoms of CARB syndrome overlap with autism, it creates a confusing clinical picture. The good news is that CARB syndrome is reversible so if you treat their CARB syndrome patients with autism tend to function much better.

http://najms.net/v06i03p158w/

Milan:

I agree that glycine is an interesting substance:

http://www.ncbi.nlm.nih.gov/pubmed/21210221

I don't think we will find a single substance that addresses this type of complex brain disorder. In my opinion a diet of whole foods addresses many of these issues. I tend to prefer Paleo myself.

https://www.google.ru/search?q=%D1%80%D0%B8%D1%81%D1%83%D0%BD%D0%BA%D0%B8+%D0%B4%D0%B5%D1%82%D0%B5%D0%B9+%D0%B0%D1%83%D1%82%D0%B8%D1%81%D1%82%D0%BE%D0%B2&newwindow=1&client=opera&hs=bZR&rls=ru&channel=suggest&tbm=isch&tbo=u&source=univ&sa=X&ei=LNF8UuHJMoHD4gT4nIHQDQ&ved=0CCkQsAQ&biw=1366&bih=602#facrc=_&imgdii=_&imgrc=gyyYRBzymtKcSM%3A%3Bw_3pPYmnNymVTM%3Bhttp%253A%252F%252Fwww.teeandcake.ru%252Fti_space%252FDevid_Bart.jpg%3Bhttp%253A%252F%252Fwww.teeandcake.ru%252Fti_space%252Fdetail%252Fblog_ti_kejk%252Fiskusstvo_v_sebe_risunki_autistov%252F%3B350%3B253

They are special. J.Mullin issued a book with their drawings "Drawing autism" Art in oneself is the peculiarity of their fantastic works. Thus, D.Bart (10 years old) painted 400 birds in his picture. His Mom said, he didn't know their names. Their exclusiveness is in harmony with their greatness.We can say about amazing capabilities of the human beings, living in their own world.

Maternal stress also one of the causative factor autism..

Well, how can researchers explain the higher level of serotonin?

Milan:

The issue of monoamine neurotransmitters and brain disorders is complex but most disorders are characterized by low functioning of these neurotransmitters. There is some evidence that processed foods can eventually lead to depletion of monoamine neurotransmitters through various mechanisms. If someone is depleted then a tryptophon rich diet won't be enough because amino acids are competively absorbed from food. I use combinations of precursors containing L-tryosine and 5-htp in a ratio of 10 to 1 to top off the monoamines so to speak, and this seems to be a good augmenting strategy for many common brain disorders.

A Paleo diet is a pre-agricultural diet that limits grains, dairy, legumes and refined sugars. Some have found it helpful for various brain disorders. Ketogenic diets also appear to be neuroprotective.

http://www.elinahealthandbeauty.com/forum/viewtopic.php?f=51&t=1408

About diet- get gut in flaming and refined sugar out of the food.

http://vk.com/paleo30

There are a lot of recepies and cooking (with photos) the dishes of Paleo. If you can't translate- I'll do it with pleasure. The main peculiarity- we bake it in oven, or froze in a fridge, or make it as a salad. I think, it's a very tasty and good diet

An interesting new paper shows the importance of zinc deficiency in autism spectrum disorders.

Gestational zinc deficiency in mice caused changes in social/maternal behaviors and vocalization patters consistent with mouse models of autism.

While gestational zinc deficiency could contribute to disruptions in brain development that cause autism, acute zinc deficiency could also be an important factor contributing to symptoms in autistic children. Acute zinc deficiency caused hyperactive behavior in mice. Furthermore, this paper shows an association between zinc status and seizures, attention deficit-hyperactivity, hypotonia, and immune dysfunction in children with an autism spectrum disorder (Phelan-McDermid syndrome).

Phelan-McDermid syndrome is associated with haploinsufficiency for the zinc binding ProSAP/Shank post synaptic density scaffold. Zinc deficiency can disrupt ProSAP1/Shank2 and ProSAP2/Shank3 and this mechanism may contribute to autism especially in patients with genetic mutations that affect this scaffold.

http://brain.oxfordjournals.org/content/early/2013/11/24/brain.awt303.abstract

"gestational zinc deficiency could contribute to disruptions in brain development that cause autism"

How would this cause much greater concordance of autism in MZ versus DZ twins?

I think an environmental risk factor could be significant even if it wasn't able to account for the greater concordance of autism in MZ vs DZ twins. The mechanism of disrupted ProSAP/Shank results from zinc deficiency and/or genetic mutations. I think multiple factors could converge on common pathways (eg. ProSAP/Shank) to disrupt brain development. Higher DZ concordance does suggest autism is highly heritable but early estimates were much higher than more recent and more rigorous studies.

Aside from direct actions on development, zinc deficiency (or other environmental risk factors) could also contribute to autism by increasing de novo mutations. I think there is still a lot to learn about the complex interactions between environmental and genetic risk factors contributing to autism and other developmental diseases.

The immediate translational relevance of zinc deficiency to symptoms among patients with Phelan-McDermid syndrome, may be the most exciting part of this research. This is in line with the thinking of William Wilson and others using nutritional therapy to manage symptoms of autistic children. Although genetic and environmental factors can disrupt brain development during pregnancy leading to irreversible effects on cognitive function, nutritional therapy may have the potential to help with some of the symptoms (eg. ADHD, hypotonia, immunodeficiency, and seizures) experienced by patients with autism spectrum disorders.

"I think an environmental risk factor could be significant even if it wasn't able to account for the greater concordance of autism in MZ vs DZ twins"

If such an environmental risk factor is as important as proposed, why should it not also affect the other twin when one fraternal twin is affected? If any toxic factor operates during pregnancy, then there are two chances of an affected child in a twin compared to singleton pregnancy. So it needs to be shown that autism is commoner in twins than singletons.

Respond to Milan's comments. Insights into the genetic landscape of ASDs have indicated substantial heterogeneity. An array of genes potentially involved in the cause of ASDs are identified. One of emerging findings reveals the pivotal role of genes that encode proteins at the neuronal synapse in Autism [reviewed in Bourgeron, 2009]. Proteins at the synapses of excitatory neurons have been linked to ASD are neuroligins (NLGN3 and 4) [Jamain et al., 2003; Laumonnier et al., 2004], neurexin 1 (NRXN1) [Kim et al., 2008], SHANK1, 2 and 3 (Durand et al., 2012; Hung 2008), sodium/hydrogen exchanger 9 (NHE9) (Garbern et al., 2010), and phosphatase and tensin homolog deleted on chromosome 10 (PTEN 10) (Redfern et al., 2010).

Indeed, intact synaptic homeostasis is a fundamental prerequisite for a healthy brain. An altered synaptic morphology and function are involved in the molecular pathogenesis of mental disorders including autism, schizophrenia (SCZ), and Alzheimer’s disease (AD) (Grabrucker et al., 2011). This theory is supported by a series of studies showing that a dysregulation of the Shank platform was found in AD models and patients (Roselli et al., 2009; Gong et al., 2009; Pham et al., 2010). Shank3 have also been associated with Schizophrenia (Gauthier et al., 2010; Bangash et al., 2011) and Bipolar disorder (Vucurovic et al., 2012) in addition to autism. Our intricate intellect is orchestrated by billions of neurons in the brain, which communicate with each other via specialised junctions called synapses. Perhaps, the factors affected synapses cound result in mental problems.

http://my.mail.ru/video/search?q=%EE%ED%E8%F9%E5%ED%EA%EE%20%F1%EB%F3%E3%E0%20%E2%E0%EA%F6%E8%ED%E0%EB%FC%ED%EE%E3%EE%20%E3%E5%ED%EE%F6%E8%E4%E0&sort=&duration=&sort_order=desc#video=/mail/strannik.nebesnyi/_myvideo/67

Onishchenko is discussing the problem of vaccination. A lot of parents think that just vaccination causes child's autism and other harmful consequences to human health..

Irena et al.: The vaccination hypothesis has been investigated and discarded by anyone reputable in autism research.

There is also an overall problem with much of the discussion of autism "risk factors" and "psychopathology" in that it relies on the assumption that there is something inherently wrong with variant forms of neural organisation.

Many of us in the field (Francesca Happe, Laurent Mottron, etc.) have come round to a different way of thinking: just as human bodies can be diverse without being pathological, so can human cognitive processes and the neural networks and genetic combinations that underlie these. Assuming otherwise is now driving a whole industry, but it reminds me of all the "science" that was done on "race" in the 19th and on into the 20th century, where darker skin was assumed to be a marker for various forms of inborn or cultural abberation that needed treatment, policing, or eugenic solutions.

Some people with autism may have impairments in the sense of diminished capacity, but these only become disabling when they are forced to learn and live in environments not adapted for their needs. It's also unclear how much of what we might term "impairment" in autism is actually produced by these conditions and not innate.

"just as human bodies can be diverse without being pathological, so can human cognitive processes and the neural networks and genetic combinations that underlie these. Assuming otherwise is now driving a whole industry"

Conspiracy theories should not be put above common-sense. The man in the street, and especially parents with affected children, can see for themselves that often, but of course not always, conditions like dyslexia, deafness, blindness, obesity, diabetes, and autism are genuine impairments and handicaps in modern society. Not everyone is happy to have these conditions, which is why they usually consult doctors to remediate them. In medicine and psychology, problems are multicausal, and can derive from both the individual and society. .

I'm not speaking in terms of conspiracy theories, but applying the social model of disability (quick introduction: http://en.wikipedia.org/wiki/Social_model_of_disability).

The social model divides impairment--the physical impact or limitation that a condition or difference may cause--and disability. Wthin the social model, disability is defined as the way individuals who have impairments (real or perceived) are presented by barriers that disable them. So as you note, an impairment can be a problem "in modern society" when it may not have been in previous times, and may not be now if we make adaptations to how we include and support people.

It isn't a question of a person "being happy to have" a condition, but of why that person may experience distress or pain. If it's an innate part of the condition (diabetes, for example, can cause one's physical health to deteriorate), then that aspect of the condition is a good target for medical treatment or other forms of intervention. If the problems associated with the condition only or mostly occur when society presents barriers to people who function differently (lack of wheelchair access for someone with a physical disability, lack of access to healthy diet for a person with diabetes, schools that teach only one way for people with dyslexia or autism, discrimination, abuse), then it's society rather than the person with the impairment that needs to be the focus of efforts for change.

Autism is so heterogenous genetically, the "risk factors" are so diverse and widely distributed, and the differences associated with it are so common (especially if one looks at the wider phenotype, as many researchers have done), that it really needs to be seen and addressed in this way.

By the way, I am the parent of a person with autism, who is now an adult, and have worked with autistic children and their families for many years, as well as carrying out research on effective interventions. In my experience, the barriers presented to people with autism by society are a much greater factor in negatve experiences and outcomes than any innate limitation conveyed by autism itself.

http://abcnews.go.com/Health/Autism/link-vaccine-autism-link-fraud-british-medical-journal/story?id=12547823&page=1

Http://www.heraldsun.com.au/archive/news/autism-study-doctor-andrew-wakefield-says-he-is-the-victim-of-smears-by-drug-companies/story-e6frf7lf-1225983329537

Irina: Wakefield didn't lose his license to practice medicine in the UK because of smears by drug companies--he lost it because he committed fraud, which was proven in an extensive professional misconduct hearing with the GMC (he also injured one of the patients in his badly-constructed study). I have never worked for a pharmaceutical company or done research funded by one; in fact, I used to work with a researcher who was friendly with Wakefield and have met him a couple of times myself. So, no personal or professional axe to grind here, just disappointment in poor research ethics, poor medical practice, and anger at mediated overhyping of inaccurate results that caused very real harm to people with autism, their families, and the wider community. I think you'll find this summary of the medical evidence more useful in evaluating the situation than news articles based on Wakefield's press releases: http://www2.aap.org/immunization/families/autismwakefield.html

I'm not a particular fan of him as a journalist, but Brian Deer's site on the Wakefield case also provides additional detail: http://briandeer.com/mmr/lancet-summary.htm

Both type 2 diabetes and autism spectrum disorders may be caused by carbon monoxide poisoning. Those cases that are caused by CO are distinguished not by maternal inflammation, which CO and many other factors may cause, but by multi-sensory sensitivity [aka MUSES syndrome], which only CO exposure is known to cause.

MUSES is a consequence of the well-documented role played by endogenous CO as a neurotransmitter that modulates the nerve action firing potential of all mammalian sensory nerves. This system normally works fine in a quickly reversible fashion but it is easily overwhelmed by exogenous CO exposure, as any inhaled CO that remains free in plasma [unbound to Hb] readily diffuses through capillary beds into tissues until equilibrium is reached.

CO control over sensory signalling may be either enhanced or extinguished as a result of CO poisoning, leaving people either hypersensitive to all types of sensory stimuli after repeated low level exposures or literally senseless [as in a coma] after a very high level exposure. Sometimes only some senses are lost, like hearing or vision, and sometimes only for a few hours or days, while in other cases sensory changes may persist for years or decades, unless and until treated.

MUSES differs from sensory integration or sensory processing disorder [SID/SPD] in that it is defined as affecting 4 or 5 of the primary senses, while SID & SPD have fuzzier definitions that encompass any combination of one or more sensory hyper- and/or hypo-sensitivities. Sensory hyper and hypo sensitivities can be screened in adults just by asking them appropriate questions, but in non-verbal children, the diagnosis depends on detecting abnormal sensory-seeking and/or sensory -avoidance behaviors in response to various stimuli.

Conditions caused by CO poisoning are also objectively biomarked by abnormal arterial-venous gaps in COHb (A >> V during exposures, while V>A post exposure) and abnormally high CO in exhaled breath.

These A-V gaps return to normal and symptoms of tissue hypoxia such as chronic fatigue syndrome and fibromyalgia as well as multi-sensory sensitivity are all gradually reversed when these cases are treated like chronic CO poisoning with daily supplemental oxygen at normal pressure.

Hyperbaric oxygen is not necessary or recommended since it actually drives arterial CO deeper into tissues and increases the risk of delayed neurological sequellae.

My protocol for adults with MUSES syndrome whose biomarkers show elevated CO in tissues recommends 100% oxygen via cannula [or partial rebreather mask if tolerated] at 5 l/m, 2 hours/day for 4 months. This gradually flushes excess CO from tissues while restoring normal tissue levels of oxygen consumption.

Treatment takes 4 months to complete because this is the lifespan of most of the heme proteins to which CO binds. The CO held tightly by these proteins (Hb, Mb, Nb, Cb, etc) is not released until they are catabolized by heme-oxygenase 1, 2 or 3. Transfusions of COHb-free blood are ineffective since they only lower the level of CO in blood without affecting the level of CO that remains in tissues.

Note that oxygen treatment does not improve all cases of autism, type 2 diabetes, CFS, or FM, just those caused by some prior CO poisoning.

If my hypothesis wrt causation is correct, the lowest rates of autism should be found among children conceived and raised in all-electric homes [without any gas, oil, coal, or wood burning devices] that also do not have an attached garage used to store vehicles. And the highest rates should be in homes with multiple sources of CO exposure.

Unfortunately, I've not yet found any autism epi studies that report on these variables, and I've not yet been able to convince any autism researchers to look at either CO biomarkers or residential CO exposures.

Anyone?

Khaled has presented a good overview of current genetic research and its potential relationship to additional factors. There are different ways of interpreting some of the results of genetic research but his explanation should be helpful to anyone who is new to the field.

It's worth noting that we already know there is no single pathway (genetic or otherwise) to this extremely heterogenous condition. Although I welcome genetic research because it helps us understand the basis for human differences, it's what we DO with this knowledge that will matter to actually existing people with autism.

If the eventual finding is that variant genetic expression can lead to differences in sensory perception and cognitive processing, and that does seem to be where research is leading us, viewing all variance as pathology is likely to lead to eugenic solutions (this is actually already happening--the extreme rhetoric around autism is already driving a nascent genetic testing industry and selective abortion).

It's much more helpful to accept that difference exists, seek to understand its nature, and adapt how we teach, support, and communicate with people who present with a variant neurocognitive phenotype. There is also a great deal we can do to reduce the barriers that autistic people encounter in homes, schools, workplaces and society.

"Neuroimaging and autopsy studies in patients with ASD suggest that brain abnormalities play an important role... Support for brain abnormalities is derived from the following observations:

●Patients with ASD have accelerated head growth during infancy and increased overall brain size (by to percent)

●Functional MRI studies indicate that individuals with ASD use different patterns of connectivity, cognitive strategies, and brain areas to process information during tasks requiring social attribution or response to visual or auditory stimuli -

●Positron emission tomography studies have shown that children with ASD have global and functional abnormalities in serotonin synthesis

●Brain electrophysiology studies indicate that individuals with ASD process information regarding faces differently , and appear to have marked delay in the neural system processing eye gaze

●Individuals with ASD appear to have neural-based deficits in recognizing and understanding speech and attending to socially relevant sounds -

●Neuropathologic studies demonstrate decreased numbers of Purkinje cells in the cerebellum"

All this shows that the brain works differently in autism, but is totally ambiguous as to whether this is the cause or result of autism. For example, I think autism is caused by fluctuant inner ear function in early infancy, whereby abnormal vestibular input would lead to miswiring of higher functions and areas, eg cerebellum, eye control, posture, intersensory integration; abnormal auditory input to disrupted cortical sensory processing, speech anomalies, audiosensitivity, etc.

To Khaled Saad: Thank you for the genetic information and other observations depicting autism risk factors. I really enjoyed reading "The Autistic Brain" by Temple Grandin and Richard Panek. Some of you may too.

Here is a link to my recent review of the topic.

Article The Plausibility of Maternal Toxicant Exposure and Nutrition...