Why the Environmental Protection Agency is important for autism

The Environmental Protection Agency has a big job to do – keep our air and water clean.  They do so, in part, with air monitors placed across the United States which allow researchers to keep tabs on what is going on in our air.  This week, a study from Dr. Amy Kalkbrenner at UWM and colleagues replicated that certain types of air pollution increased risk of autism, as well as increased symptoms of severity of autism in those with a diagnosis.   These pollutants come from cars, but also coal burning power plants.  This new research calls for more action, not less, by the crucial staff and infrastructure of the EPA and policy to help support them do it.  #standwithEPA

https://ehp.niehs.nih.gov/ehp1867/

 

What is true for males is not true for females

This week’s podcast focuses on the Extreme Male Brain Theory of autism, originating from the idea that autism, in part, is a reflection of increased fetal testosterone levels.  Amazingly, fetal testosterone levels are reflected in the length of the 2nd and 4th fingers and can be measured as a reflection of testosterone levels during pregnancy. Research, including those from a recent CDC study, have reinforced that elevated fetal testosterone levels play a role in autism in males, but not females.  Differences in fetal testosterone across gender and diagnosis has also been observed in a study from Drexel University.  What was observed in males is not observed in females.  It doesn’t mean the theory is wrong, it means that what is true for one sex is not always true for the other.

https://www.ncbi.nlm.nih.gov/pubmed/29450837

 

What is the real prevalence of ASD?

Unfortunately this podcast does not really provide an answer, but does highlight data published over the holidays which shows in another dataset, that the prevalence of autism seems to be leveling out, rather than continue to increase as it has done for the past several decades.  It isn’t the final word and clearly there may be exceptions, but now two national datasets have shown no further increase in autism prevalence in the last few years of looking.  Is it 1:68 as reported in one study or 1:39 in another?  Is it somewhere in between?  Still to early to say, but white boys seem to be the most likely to get a diagnosis no matter where you look.  Also, folic acid proves to show an effect on the probability of not just an autism diagnosis, but autism symptoms.  This is especially important for women taking anti epileptic medications for seizures and bipolar depression.  Welcome to 2018!

Here are links to the articles.  Some of them are open access!

https://www.ncbi.nlm.nih.gov/pubmed/29297068

https://www.cdc.gov/nchs/data/databriefs/db291.pdf

https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2667432

https://www.ncbi.nlm.nih.gov/pubmed/29279889

 

 

Pregnant and concerned about autism? Folic acid can help.

This week a bunch of new studies came out that focused on changes in probability of having a child with autism after folic acid consumption during pregnancy.  Moderate consumption folic acid and slightly elevated levels of plasma folate during pregnancy has now been shown in at least half a dozen scientific studies to reduce the chance of that child to be later diagnosed with autism.  This is not a prevention effect, but a reduction in probability.   There are enough studies on this question for a Chinese group to have organized them, put their data together, reanalyze them together and conclude that this is a real thing.  If this was an effect seen after say, drinking battery acid, maybe it might require more consideration to recommend to the community.  However, taking folic acid during pregnancy is something medical doctors are recommending pregnant women do anyway.

Want to learn more?  Here are the studies:

Swedish Study:  https://www.ncbi.nlm.nih.gov/pubmed/28978695

http://onlinelibrary.wiley.com/doi/10.1111/ppe.12414/epdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5625821/pdf/13229_2017_Article_170.pdf

Denmark Study:  https://www.ncbi.nlm.nih.gov/pubmed/28946926

 

What is the microbiome and why should families with ASD care?

This week’s ASF Podcast is a special interview with Dr. Gil Sharon from CalTech, who studies the microbiome in animal models and potential link to ASD.  The microbiome is the full community of bacteria that live in our bodies and outnumber cells 10-1. They can affect the genome directly and they can respond to environmental factors which means they may be a site for important gene x environment interactions in autism.  Some people with ASD, especially those with gastrointestinal problems, show alterations in the microbiome and more and more scientists are starting to incorporate studying this complex system into their research.  Most importantly, new research is suggesting potential for probiotic therapies to not only treat GI symptoms, but also core autism symptoms.  If you like the podcast, Dr. Sharon has provided a list of resources which can provide more detail:

Interventions in mice –

Hsiao, E.Y., McBride, S.W., Hsien, S., Sharon, G., Hyde, E.R., McCue, T., Codelli, J.A., Chow, J., Reisman, S.E., Petrosino, J.F., et al. (2013). Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155, 1451–1463.

Buffington, S.A., Di Prisco, G.V., Auchtung, T.A., Ajami, N.J., Petrosino, J.F., and Costa-Mattioli, M. (2016). Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring. Cell 165, 1762–1775.

Intervention in humans –

Kang, D.-W., Adams, J.B., Gregory, A.C., Borody, T., Chittick, L., Fasano, A., Khoruts, A., Geis, E., Maldonado, J., McDonough-Means, S., et al. (2017). Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome 5, 10.

Microbiome profiling –

Gondalia, S.V., Palombo, E.A., Knowles, S.R., Cox, S.B., Meyer, D., and Austin, D.W. (2012). Molecular characterisation of gastrointestinal microbiota of children with autism (with and without gastrointestinal dysfunction) and their neurotypical siblings. Autism Res. 5, 419–427.

De Angelis, M., Piccolo, M., Vannini, L., Siragusa, S., De Giacomo, A., Serrazzanetti, D.I., Cristofori, F., Guerzoni, M.E., Gobbetti, M., and Francavilla, R. (2013). Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified. PLoS One 8, e76993.

Son, J.S., Zheng, L.J., Rowehl, L.M., Tian, X., Zhang, Y., Zhu, W., Litcher-Kelly, L., Gadow, K.D., Gathungu, G., Robertson, C.E., et al. (2015). Comparison of Fecal Microbiota in Children with Autism Spectrum Disorders and Neurotypical Siblings in the Simons Simplex Collection. PLoS One 10, e0137725.

 

The Final Word on Antidepressants and Autism Risk???

Every time you turn around there is another study contradicting the last on antidepressant use and autism risk.  An answer on why there are differences across different studies may be found in a new analysis published by University of Washington and SSM Dean Medical Group in Wisconsin this week.  They showed that autism severity (not risk) is increased only with both a likely gene disruption AND following antidepressant exposure in pregnancy together.  This suggests a double hit model similar to other complex neuropsychiatric disorders like depression.  It also suggests that findings from other chemicals, like PBDE’s, may be dependent on gene / environment interactions too.  After all, a new systematic review showed PBDE’s during pregnancy are bad for the IQ of the child.  This provides insight on ASD risk and subtype given the multitude of possible genetic / environmental combinations out there.

Chromosome 15-apallooza

One of areas of genetic interest of autism is a region of chromosome 15.  Only about 3% of people with autism have the mutation, but 80% of those with the mutation have autism.  It is so important that people with duplications of this area have formed their own advocacy group called the Dup15 Alliance.  I was honored to attend their family an scientific meeting and give a summary of what scientists have learned about autism through studying this chromosome, how kids with this mutation and autism are similar and different from those with autism but not the mutation, how the families are managing life threatening seizures, what the gene does, what the brains look like, and how mutations of this chromosome do in fact interact with the environment.  Thank you to the scientists who study this area and the very brave, selfless and amazing parents who I talked to.

The Benefits of Being and Older Father

Advanced paternal age is one of the more replicated risk factors for autism – but maybe not autism as it as seen as a disorder.  Recent studies by Mount Sinai School of Medicine and Kings College of London show in both animal models and in epidemiological studies that advanced age in fathers is associated with the “active but odd” phenotype and PDD NOS.  In people, older (but not “old”) age in fathers led to increased IQ and social aloofness that led to higher academic achievement.  Is this autism?  Or just a subtype of autism where the outcomes are adaptive rather than maladaptive?  There are lots of questions about the nature of autism in these findings.

Internet addiction is a real thing and it is worse in kids with autism

Two studies of importance came out this week.  The first looked at the interactive effects of genetic mutations called copy number variations and air pollution.  Previously, ozone was not listed in the factors in air pollution that increased risk for autism.  But combine it with copy number variations – now the two together dramatically increase risk.  Ozone levels are something that can be reduced through legislation.  Second, the role of internet addiction is generally not acknowledged or appreciated, but a recent study demonstrated that people with autism show triple the rate of internet addiction compared to those without autism.  This is something that psychiatrists and psychologists should know about when they think about treatments and comorbidities of people with ASD.

Webinar: Investigating gene x environment interactions in “single gene” autisms

On May 4th, Dr. Janine LaSalle from UC Davis and (the soon to be Dr.) Keith Dunaway presented on recent research investigating the role of environmental factors in individuals with Dup15 Syndrome.  Individuals with a mutation on chromosome 15 are often diagnosed with autism and previously it had been assumed that these individuals were destined to have a diagnosis due to their genetics.  Dr. LaSalle shows that many of the genes in a critical region of chromosome 15 are tied to turning genes on and off via a process called methylation.  Environmental chemicals or other exposures may also work on these genes to turn on or off gene expression epigenetically.  The first half of the webinar reviews crucial ideas in gene x environment interactions and epigenetics, the second half describes experiments using brain tissue of those with Dup15 Syndrome and autism, as well as cell lines, to understand the role of PCBs in gene expression.