The world of autism is a diverse one—autism and autism spectrum disorder are general terms for a group of complex and extremely heterogenous life-long neurodevelopmental conditions. Autism is also one of medicine’s greatest challenges. The current general consensus is that autism has multiple causes, and these causes can be as varied as the types of autism, which are not very well defined, yet. It is almost certain, though, that autism has its roots in very early brain development, development that can be influenced by a variety of factors. Results from different studies indicate that alterations in the mother’s immune system during pregnancy, especially those resulting from viral infections and occurring during key early periods of fetal neurodevelopment, may play a role.
In 2010, a large study, which included all children born in Denmark between 1980 and 2005, highlighted an association between women who suffered an infection severe enough to require hospitalization while pregnant, and the presence of autism spectrum disorder (ASD) in their offspring: mothers who experienced a viral infection in the first trimester, or a bacterial infection in the second trimester, were much more likely to have a child with ASD. This phenomenon can be modeled in pregnant mice subjected to immune activation with specific antigens.
Now, results from a study recently (February 26, 2016) published in the journal Science (The maternal interleukin-17a pathway in mice promotes autismlike phenotypes in offspring) reveal a possible mechanism at the basis of the previous observations. The researchers injected pregnant mice with synthetic double-stranded RNA, a mimic of viral infection that induces severe inflammation. They found that the induced inflammatory response in the mother activated cells that produce a messenger molecule, or cytokine, called IL-17. This cytokine appears to interfere with brain development.
Gloria Choi, lead author of the study, said in a press release: “In the mice, we could treat the mother with antibodies that block IL-17 after inflammation had set in, and that could ameliorate some of the behavioral symptoms that were observed in the offspring. However, we don’t know yet how much of that could be translated into humans.”
Next, the researchers found that mouse brain cells in the developing fetuses of mothers experiencing inflammation express receptors for IL-17. Exposure to IL-17 may induce the brain cells to produce even more receptors for IL-17, amplifying its effects. In addition, the researchers found irregularities in the normally well-defined layers of cells in the brain’s cortex of developing mice, where most cognition and sensory processing take place. These patches of irregular structure appeared in approximately the same cortical regions in all of the affected offspring, but they did not occur when production of IL-17 was blocked in the mother. Disorganized cortical layers have also been found in studies of human patients with autism.
Choi added: “We’ve shown correlation between these cortical patches and behavioral abnormalities, but we don’t know whether the cortical patches actually are responsible for the behavioral abnormalities. And if it is responsible, what is being dysregulated within this patch to produce this behavior?”
The researchers plan to investigate, in mice, whether or not the genetic makeup influences the susceptibility to maternal inflammation—indeed, autism is known to have a very strong genetic component. In final analysis, the researchers hope that their work will help in designing strategies that could prevent autism development in children of mothers who experience severe infections and inflammation during pregnancy.
I certainly think the genetic makeup of the mother influences the susceptibility to maternal inflammation, perhaps in conjugation with environmental factors as well? This post stated that the researchers found that mouse brain cells harvested from the developing fetuses of mothers experiencing inflammation expressed the receptor for cytokine IL-17, a product of the induced immune response that appears to interfere with brain development.
Studies have shown a link between stress and weakened immune system as a result of stress. As the same neuropeptides mediate both stress and inflammation (Link 1), I think it would be interesting to see if there is any correlation between mothers experiencing extreme stress (whether she was innately a worry wart, had a difficult pregnancy, etc) and autism. Stress hormones are able to cross the placenta, thus exposing the fetus to the possibility of damaged neurological functioning. Children born with austism also have a depressed immune system, producing much lower levels of IgG when compared to other kids (Link 2). Exploration of possible stress-related environment during infant development in relation to autism would also be interesting. “Nature vs Nurture” may play a major role in autism as autism may be a product of changes in their neuronal microenvironment, both in utero, and once the child was born. Take for example, identical twins. At birth, their DNA is exactly identical; Over time, their DNA changes in response to different environmental changes they individually encounter as they age. Could a mixture of nature vs. nurture result in the neurodevelopmental condition associated with austism?
The effect of stress can be seen with its association with several of the leading causes of death: heart disease, cancer, chronic lower respiratory infections, Alzheimer’s disease. Stress may not directly cause the occurrence of these conditions, but it can tremendously exacerbate the severity of these disease by participating in the inflammation associated with these diseases. Researcher McCallister and her team at UC Davis are studying changes in MHC 1 molecule located on neuronal cells that may contribute to autism by altering synaptic connectivity of developing neuronal cells, suggesting that cortical patches may not be the sole cause of autism, but in conjunction with environmental factors that induce changes to the developing neuronal cell that may also contribute to autism.
1. http://www.ncbi.nlm.nih.gov/pubmed/12480495
2. http://www.ucdmc.ucdavis.edu/welcome/features/20080305_mindmatters_immune/
While I think you raise a good point about stress inducing a weakened immune system within the mother and possibly having effects on the fetus as it pertains to neurodevelopment disorders, I definitely don’t think the the same mechanism could be implied simply by inflammation from stress. The article you referenced cited stress inducing the production of cytokines IL-1, 4, and 6 mainly, whereas ta he study in the original post was Il-17a. After a little digging I noticed the vast differences in molecular structures between these (and all, really) cytokine molecules. So if stress could indeed be implicated in the cause of autism, I think it’s safe to assume a different mechanism is at work here. In fact the original study proves that Il-17a is necessary for AD presentation in MIA induced mice.
I did, however, find a review compiling information about prenatal stress and its relation to autism in children. It cites a couple articles showing pretty conclusive links between prenatal stress events and children with AD, but also importantly identifies errors with the studies’ scientific methods. In effect, the link between prenatal stress can still not be conclusively proven. The review also categorizes potential mechanisms for prenatal stress causing autism, yet none of these include possible links to inflammation and its effect on neurodevelopment. I think research would be more effective if used to narrow down existing leads rather than beginning anew.
http://www.sciencedirect.com/science/article/pii/S0149763408000985
Actually, I agree with Ltran stress can be a cause of inflammation in pregnant women, however, I would think maybe a more severe level of stress for continued periods of time. Genetic and Environmental factors can cause the inflammation that leads to Autism. The article Heathline discusses the concept of inflammation, which is the body’s way of attacking foreign material that try to invade the cells of the body. More importantly. It discusses how repeated immune responses are not good for some pregnant women and that may be the cause of the inflammation. Studies show that women who are immunocompromised, such as asthma, rheumatoid arthritis, diabetes, obesity, or any cell disease are more prone to inflammation, . Similarly, the article discusses how people who are immunocompromised respond aggressively to stress, which causes inflammation that can also lead to Autism to offspring. As stated earlier, both stress and genetic diseases or disorders can affect pregnant women because they can both contribute to inflammation;it really depends on the female because everyone is composed differently, with various defense mechanisms and abilities to handle certain situations.
References
http://www.healthline.com/health-news/connection-between-inflammation-and-autism-052214#3
I failed to mention chronic stress as the source of inflammation (as stated by Cristina O.) that may have a contribution to the development of autism. Although a link between prenatal stress and autism cannot be proven, I certainly believe it can very well be a contributing factor as autism has origins that encompass many different factors that are not well understood. IL-1 is involved with immune system regulation and inflammation; IL-4 is involved with B cell proliferation, and Il-6 is involved with B and T cell differentiation, as well as NK cell activation. Although the original reference ‘proves that Il-17 is necessary for AD in mice,’ it does not negate the possible involvement of other interleukins as autism occurs as a result of an accumulation of factors; IL-6 is an interleukin involved in both the adaptive and innate immune defense, and thus the inflammatory response. Furthermore, Choi, a researcher in that study states that a correlation between IL-17 production (resulting in cortical patches) and behavior abnormalities have been deomonstrated, but it is not known if there is a causal relationship between Il-17 production and behavior abnormalities. I am not inferring that stress is simply a cause of autism, however I do believe that there is reason to study the effect of stress (both prenatal and developmental) and possible links to autism.
Side note: I learned in abnormal psychology that the low socioeconomic demographic of people tend to have more schizophrenic individuals when compared to other socioeconomic classes; and this is thought to be related to the large amount of stressors that dominate said class. Emerging studies have shown a link between autism and schizophrenia as both disorders share similar clinical features. This finding further underscores the importance of understanding contributing factors that lead to the development these disorders, as it is understood that there in not one definite cause, but rather an accumulation of factors that make an individual more susceptible to developing these disorders.
http://www.emaxhealth.com/12577/autism-and-schizophrenia-there-connection
Autism spectrum disorder is characterized by a neurological defect that leads to deficits in behavioral and social norms. Many have speculated on the cause of autism as its incidence increasingly rises. The study suggests that mothers infected with a viral or bacterial illness during particular times of gestation have increased rates of children born with autism due to the inflammatory effects on the fetal neurodevelopment caused by the illness. Environmental causes are also being studied as a possible causative agent for autism. In a study by Kilburn, et.al, there were increased rates of children suffering from autism when they had previously been exposed to mold or a mycotoxin. Children who had been exposed to mold or mycotoxin had obvious neurobehavioral impairments including balance, reaction time, color discrimination, concentration, recall memory, multitasking, and long-term memory. The rates of autism spectrum disorder in the children who had been exposed were 24 times higher than the national autism spectrum disorder rates. It would be interesting to see if any of the children from the study on inflammation had previously been exposed to an environmental agent and if there is perhaps a greater link to a child’s environmental factors leading to autism.
http://eds.b.ebscohost.com.ezproxy.gsu.edu/eds/pdfviewer/pdfviewer?vid=5&sid=342d22f8-1620-43b2-8fd7-28cf2081dcd9@sessionmgr120&hid=126
It would seem that previous exposure to mold and/or mycotoxin would induce an inflammation response, in turn, triggering an increase release of the IL-17 cytokine which is linked to interference in brain development. In your article, are the children exposed to the mold/mycotoxin during gestation, or have they been exposed post-birth? In any means, you pose an interesting research question of whether environmental causes or intrinsic/extrinsic pathogenic causes have greater effects on autism development. I too, would like to see the analysis of these factors in comparison. However, I think it would be more interesting to determine the risks associated with each factor in relation to embryonic development. That is, expose pregnant mice to both infectious pathogens and environmental toxins and evaluate the effects on autism development during pregnancy. Great blog post.
As aforementioned in the article, autism in general is one of medicine’s greatest challenge. This is due to its massive underlying causes with some risks factors being currently identified while others are still in discovery. This article mentions a study done on autistic children whose mothers suffered from severe infections during pregnancy and how they were likely to produce children with autism. What the article does not mention is the impact of probably the drugs administered to the mother during the course of the infection. Most drugs today bring more harm than good and this is because of the wide range of effects of the drug. And there many studies being done on effects of different drugs and prenatal autism development. For instance, one research did a longitudinal study of pregnant women who took Valproate- a drug used in treatment of epilepsy, migraine headaches and mood disorders and its risk in prenatal or childhood autism. The found that pregnant women exposed to this drug had autistic children. So in conclusion, it would really interesting to know what kind of drugs these pregnant women took if any at all and if those drugs could have a contributory factor to the children being diagnosed with autism.
Reference:
Singh, S. (2013). Valproate use during pregnancy was linked to autism spectrum disorder and childhood autism in offspring. Annals Of Internal Medicine, 159(4), JC13. doi:10.7326/0003-4819-159-4-201308200-02013
You bring up a valid point about how medications given during gestation could possibly cause neurodevelopmental disorders such as autism spectrum disorder. I found another study which also tests this possibility. In this particular study, the researchers found an increase in autism in those whose mothers had been taking selective serotonin reuptake inhibitors. SSRIs are commonly given to pregnant women dealing with depression. It showed that these children had increased deficits in their speech, behavior, and social-emotional status as compared to children whose mothers had not been taking SSRIs. Also, ASD was more prevalent in these children exposed in utero than those who were not. The results from these studies definitely call for further the exploration of the idea that prenatal pharmacological administration could put a child at risk for autism. If there does prove to be a link, hopefully they will be able to come up with safer treatment options for these mothers.
http://eds.b.ebscohost.com.ezproxy.gsu.edu/eds/pdfviewer/pdfviewer?vid=3&sid=d55c1395-0f95-4753-ad13-58409fd63025@sessionmgr115&hid=127
SM,
I think you bring up a great point! It would have been very useful if the article did mention which drugs were given because as can be seen in the case of Valproate, there is several research linking this drug to autism. In a 2014 research article published in the “Neuroscience Letters”, long term fetal exposure to the drug did show in animal models that there was disturbance of brain development that resulted in irregular organization of the cortical structures, overgrown frontal lobe, and an increase in neuronal cell numbers. Another study supports the point that you have brought up and the research article that I previously mentioned. Hyo Sang et.al 2014 has also reported about this increase in neuronal numbers. While in development, there is a decrease in neuronal progenitor cell death in fetuses whose mothers are taking Valproate. The process of neuronal cell differential and apoptosis of neuronal progenitor cells is needed for fetus development. So yes, I completely agree with your argument Valproate and possibly, other drugs are harmful to pregnant women.
Now I do feel that there is a small flaw in your argument. I am curious to know why you feel that more drugs do harm than bad. Other than what you have presented here about Valproate, do you have any other examples you can provide to support this argument? In addition to this, you did state that Valproate is given to treat epilepsy, migraines and bipolar disorders. The article is describing women who were treated with either ANTIBIOTICS or ANTIVIRAL drugs. Just from our knowledge in biology, the mechanism of these will probably be much different than a drug used for the reasons Valproate is used. In my research, I discovered two different articles in which the mothers were treated with antivirals. Both research teams concluded that it is not the drugs themselves, yet they believe the mother’s immune response mediated by cytokine activation is what could contribute to the changes in the fetus brain. This is a similar argument presented by the research referenced in the article. In no way I am saying you are wrong, I just am interested in seeing some cases in which an antibiotic or antiviral has been discovered to be at fault for developmental brain changes.
References:
Sabers, A., et al. (2014). “Long-term valproic acid exposure increases the number of neocortical neurons in the developing rat brain. A possible new animal model of autism.” Neurosci Lett 580: 12-16.
Go, H. S., et al. (2011). “Valproic acid inhibits neural progenitor cell death by activation of NF-kappaB signaling pathway and up-regulation of Bcl-XL.” J Biomed Sci 18(1): 48.
Shi, L., et al. (2003). “Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring.” J Neurosci 23(1): 297-302.
Patterson, P. H. (2002). “Maternal infection: window on neuroimmune interactions in fetal brain development and mental illness.” Curr Opin Neurobiol 12(1): 115-118.
I completely agree with you. After reading the article I also wondered what other factors could come into play with the development of autism. My initial thought was also the vaccines given to the pregnant mothers that have a viral or bacterial infection. Upon doing research however, I found that they have already started testing different vaccines and there relation to autism. One being Thimerosal in the flu vaccine. The experiment was performed by the CDC. They evaluated the children’s exposure to ethylmercury, which is located in thimerosal. There was 256 children with ASD and 752 children without it. The results showed the children had the same amount of exposure to ethylmercury. This gives the conclusion that vaccines with thimerosal do not lead to autism.
http://www.cdc.gov/vaccinesafety/concerns/thimerosal/study-risk-autism.html
This is an interesting take on the issue of vaccinations. As it is well known, the famous British study linking vaccinations in early childhood years to the onset of autism has been retracted and publicly, explicitly concluded to be a fraudulent study. However, even after all of the decades of research AGAINST this study as well as the evidence of fraudulent and unethical behavior from the lead author, there are many who still trust it and refuse to vaccinate their children. This particular study involved the measles, mumps and rubella (MMR) vaccine. While this controversy has impacted vaccination rates and therefore the rate of once eradicated diseases in the world, there is no link between early childhood vaccinations and ASD. While this study, and subsequent studies focused on the vaccinations of children, it was not interested in investigating the connection between pregnant mothers being vaccinated and the impact on fetal development in the womb. I would not have originally thought about the issue of pregnant mother vaccinations due to the fact that most vaccines are given during the childhood years not the child bearing years, however, I was forgetting the annual flu vaccination as well as booster shots such as tetanus (every 10 years). If a woman should be due for her tetanus booster during a time when she happens to be pregnant, should she wait until she’s post-partum to obtain it? In doing some research, I found that the American College of Obstetrics and Gynecologists (ACOG) did not present any research showing that the TDAP (vaccination against tetanus, diphtheria, and pertussis) had any adverse reactions on the development of the fetus in utero (link 3). While they do not include studies regarding the development of the child in postnatal development, they focus mostly on the risk of not protecting infants from these deadly diseases. Perhaps further research could look into the effects further in development of the children exposed to the TDAP vaccine in utero. While it has been debunked that the MMR has any impact on autism from the vaccination itself, there may be some response (not only from the mother mounting an immune response) but also to the fillers used (as mentioned above). There are so many underlying factors and influences that dictate whether or not a person will get autism, being able to narrow down the field and pinpoint one aspect of the mystery may lead the way to uncovering ways in which to prevent it. One thing is for sure, there is no quick and easy solution.
Links:
1) https://www.sciencebasedmedicine.org/lancet-retracts-wakefield-article/
2) RETRACTED: Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children, Wakefield, AJ et al., The Lancet , Volume 351 , Issue 9103 , 637 – 641
3) http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2897%2911096-0/abstract
http://www.acog.org/Resources%20And%20Publications/Committee%20Opinions/Committee%20on%20Obstetric%20Practice/Update%20on%20Immunization%20and%20Pregnancy%20Tetanus%20Diphtheria%20and%20Pertussis%20Vaccination.aspx
I almost jumped at the previous post for suggesting vaccinations cause autism as well until it occurred to me that vaccinations during pregnancy indeed have little or no research available. It’s an interesting thought, however I tend to think that if vaccines have no detrimental effect on early age children they would also have little or no effect on fetuses. Of course, fetuses are much more sensitive during development to a variety of substances compared to children (after birth). However, the substances ingested (or injected) by mothers dissipate or are absorbed and therefore not nearly as concentrated once they reach fetuses (most of the time). With such minute amounts of fillers to begin with, I highly doubt they could effectively influence fetal development. This is just my own hypothesis, but I would suggest that if any side effects result from vaccinations it would indeed be from the secondary inflammation effects as suggested by this study, not from the substances within the vaccine directly.
There has been an increased rate in children who have autism, and it has been a great concern that it has been really hard to cure and treat. There are many risk factors to this, including mothers obtaining infections during their pregnancy. However, a major factor that was not mentioned was age. The older the mother is, the higher the chance that the offspring will develop a birth defect of any sort, especially autism. A study was performed where 47 children born to mothers above the age of 35 were tested to see if ectodermal cells were abnormal or not regulative. Ectodermal cells are part of the epigenome, which connects environmental changes to the offspring’s development in gestation. It was observed that the dysfunctional epigenome had a direct correlation to the individuals with autism. This could have been due to the mother’s eggs aging, or her eggs could have affected from the environmental changes. Ultimately, this could have caused a mutation on the epigenome, which could have resulted in autism.
With age comes weakened immunity, and a mother who is older than 35 is at risk of giving birth to a child with autism because they can also contract other infections. Research has shown that older mothers who are pregnant are more likely to contract infections during pregnancy and pass them onto the fetus because of weakened immunity.
There are some mothers who are bearing children later in their lives, and one of their concerns is that their child should be healthy. Is there any way to have children above the age of 35 and confidently know that the child will not have any birth defects, let alone autism? It would be interesting to see if there are any novel techniques to help mothers above the age of 35 to have a baby who is healthy and autism-free.
I must agree that you bring up an excellent point. Due to changes in lifestyle over the years, women have emerged to become much more than house wives. Many are pursuing long careers to assume prestigious jobs as working businesswomen, surgeons and lawyers. As the taboo of gender equality is being torn down, having children is becoming less of a priority and an idea that is more so being placed on “hold”. In fact, a study revealed that the more educated women are becoming, the later motherhood begins. The study revealed that 34% of women begin to have children over the age of thirty. Autism Speaks reported that the risk of having a child with autism was about 50% more for a thirty-five year old mother than a mother in her mid to late twenties. These numbers show an association between parental age and autism that seem to correlate with the increased numbers of children affected by Autism within the past twenty years. Furthermore, a study conducted at Yale University showed a correlation between mutations in the DNA of children with autism and the increasing age of their fathers. This brings me to add, Knox, that while weakened immunity in older mothers could be contributing to rising numbers in ASD, perhaps the problem is occurring at the genetic level. Studies reveal that mutations rise due the continual division of cells that persist as we age. The continual generation of sperm in older fathers is believed to give way for the acquisition of mutations with each division. Although mothers are born with a supply of eggs, studies show that problems arise from intact eggs over time, essentially affecting how well a cell divides and therefore resulting in chromosomal issues. Perhaps there is a way to slow and regulate the divisions of these cells in older men and women seeking to have children to prevent genetic mutations that can lead to ASD.
http://www.pewresearch.org/fact-tank/2015/01/15/for-most-highly-educated-women-motherhood-doesnt-start-until-the-30s/
http://www.nature.com/news/fathers-bequeath-more-mutations-as-they-age-1.11247
Autism and autism spectrum disorder (ASD) are disorders in brain development. 1 in every 68 American children has it. The cause isn’t unknown, it doesn’t exist. However there are causes in question, which are being researched to this day. One new thing is the correlation between epigenetics and autism. Epigenetics is the environmental factors that affect gene expression. (link 1) This isn’t just referring to pollution or the foods you eat; it’s also referring to the chemicals around the DNA. This includes the research discussed in this paper. The way a mother’s maternal inflammation affects the neuronal cells types and their connectivity. I believe the next step to discovering the different causes of autism and ASD is to take all the different epigenetics factors into account. When testing mice or following the pattern of women who gave birth to autistic children, I think all factors should be documented not just if they had a viral infection or bacterial infection and when. There are other factors that should be added to the mix. In the ‘Maternal Infection During Pregnancy and Autism Spectrum Disorders’ article (citied in the paper above), researchers only looked at women with bacterial and viral infection. What about the women that don’t have bacterial or viral infections that still give birth to autistic children? What other things were going on in their life that might increase the likelihood of them giving birth to autistic children? There is a known positive correlation between epigenetic and medication, stress and more. (link 2) I believe all these things should be tested and observed together, not separately. This will get us closer to discovering the causes of autism and ASD.
https://www.autismspeaks.org/node/123021
file:///C:/Users/Tiffany/Downloads/ijerph-10-04261.pdf
As mentioned in the article, autism in children is triggered by complications during pregnancy such as inflammation due to viral or bacterial infections. Moreover, autism can also be caused by alteration of cortical neuronal migration during the pregnancy. In fact, for neuronal migration to occur, there shall be the presence of T3, which is produce by de-iodination of T4 by fetal brain de-iodinases. Studies showed that hypothyroxymenia, which is characterized by the low production of T4 in mothers, causes low T3 in the brain of fetus during the period of neuronal migration, and it alters the fetus’ brain, therefore leading to autism.
What exactly causes hypothyroxemia in pregnant women? Pregant women that ingest dietary flavonoids affect their maternal thyroid function. In fact, those flavonoids inhibit the de-iodinases D2 or D3. Furthermore, the ingestion of plant isoflavonoids has many effects on the thyroid hormones and on the hypothalamus-pituitary axis. Therefore, besides viral or bacterial infections, dietary intake of pregnant women can also be the cause of autism in their children.
To think outside of the box, will mean asking questions like why doctors know the impact of those dietary intake and still give it to pregnant women?
http://www.jns-journal.com/article/S0022-510X(07)00437-6/fulltext
The topic of autism in children comes with a lot of ambiguity of the cause of this disease in children. There are many factors that can contribute to a child being diagnosed with autism such as: Age, drugs administered during gestation, even environmental pressures aforementioned. One possibility that has not come into question is, is there a recessive gene that mothers carry that can be passed down to the offspring that causes autism? Researches study the fact that there could be a rare genetic variant that is cause of autism, they also speculate that the genome can have junk coding and during development of the baby this junk coding can indeed be expressed. It is hard to pinpoint a disease on a specific cause because there are simply many cases that are unique to every situation, not all mothers over the age of 35 have babies with a disease or simply a nature or nurture situation for example, yes they can be contributing factors but not in the grander scheme of things. That is why I prose the question of genetics, it is a logical question because everything starts with the genome and everything can be traced back to ancestral genes which in this case is important in finding out more about autism disease in pregnant women.
http://hub.jhu.edu/2015/03/25/autism-genetic-cause
Knox,
I knew someone would make it as simple as the genome relating to autism! I took Genetics here at GSU and we covered the genes associated with Autism briefly. As it turns out, autism linked genes are all over the genome in humans. It’s been reported that 20 out of our 23 passed down chromosomes have shown autistic connections. A study was actually done on a “rare genetic variant” as you mentioned in your post. The shocking research showed that, yes a genetic variant could cause Autism but it can also decrease cancer rate at the same time. Adults and children with ASD were shown to have a resistant effect to cancer, but this effect faded with age. I agree with you that autism is ultimately coded for somehow by the genes received from the parents. It’s amazing to know what all our genes can create for us. A small mutation/variant somehow causes autism, but could also prevent that person from developing cancer. This connection is causing so many discussions and research about cancer-targeting drugs supplying therapeutic effects for autistic patients.
Reference:
http://www.ncbi.nlm.nih.gov/pubmed/26934580
http://genetics.thetech.org/original_news/news49
The thing about autism is that it cannot be broken down into a simple “autism gene”.
The link I cited earlier could also be of some use to you guys, as there are many questions still remaining regarding gene theory and autism. For instance, while monozygotic twins (genetically identical) have a higher occurrence of autism in both twins than dizygotic twins, there are environmental differences within the womb in these two situations that could account for this occurrence disparity.
Neurological development is so complex, and requires perfect interaction between so many molecules, part of me highly doubts scientists will ever narrow down one precise cause of autism, especially considering the wide spectrum of autistic disorders. Symptoms of autism variants overlap with symptoms of many of mental disorders such as ADD and ADHD, depression, and many other much more severe disorders such as bi-polar and schizophrenia disorders. Autistic children are often under or misdiagnosed, and sometimes even over diagnosed.
Any sort of mistake during neurological development could lead to a small decrease in natural function for these children, thus leading to the wide and varied AD spectrum. And these types of mistakes happen all the time, for a variety of reasons, whether it be emotional stress, biological (illness related), drug use (recreational or medicinal), or chemical. If it were as simple as a gene, the disease too would be simple.. but that’s just not the case.
http://www.sciencedirect.com/science/article/pii/S0149763408000985
I agree completely that autism is far too complex to pin down to one specific cause or factor. I also think it’s interesting that you cited the higher occurrence of autism in both twins in monozygotic twins compared to both twins in dizygotic twins. But if I may play devil’s advocate for a moment, I would say that inflammation of the brain in developing fetuses is a strong contender for the cause of autism (if we were to accede that autism could really be caused by any one thing). Here is a possible explanation for the twin study you spoke of: it is possible that the difference we observe in the occurrence of autism rates in both twins in monozygotic twins is that monozygotic twins are identical and have no genetic variation between each other and so whatever causes inflammation of the brain in one twin will also cause inflammation of the brain in the other twin (all other factors in this particular case are the same, same womb, same external environments). If we take this assumption to be true, it is feasible that dizygotic twins have enough of a variability in genetics that when one twin suffers brain inflammation that leads to autism (again, this is an oversimplified view for the sake of the thought experiment), the other twin does not suffer brain inflammation that leads to autism (maybe this twin is naturally genetically predisposed to lower inflammation or has greater inflammation regulation leading to a surprisingly low amount of inflammation throughout its life). With this explanation and interpretation, there is strong agreement with the observation that monozygotic twins tend to have a higher occurrence of autism in both twins than dizygotic twins.
Tanderson,
When I took genetics at GSU, sadly we did not cover the topic of autism and the possibility of the disease preventing cancer. You are right when you say there is a lot more research to be done. Cancer approximately affects 1 in 2 people which is an epidemic that scientist are eager control and cure. If there was a possibility to manipulate the genomes of an autistic patient to down regulate cancer cells and rid the body of cancer completely that would be amazing similar to the idea of a vaccine. So i prose the question of, is there a way for at risk mothers who are heterozygous/ homozygous dominant for the autism gene be able have gene therapy as a preventative measure of having a child with autism?
As mentioned in the article, autism in children is triggered by complications during pregnancy such as inflammation due to viral or bacterial infections. Moreover, autism can also be caused by alteration of cortical neuronal migration during the pregnancy. In fact, for neuronal migration to occur, there shall be the presence of T3, which is produce by de-iodination of T4 by fetal brain de-iodinases. Studies showed that hypothyroxymenia, which is characterized by the low production of T4 in mothers, causes low T3 in the brain of fetus during the period of neuronal migration, and it alters the fetus’ brain, therefore leading to autism.
What exactly causes hypothyroxemia in pregnant women? Pregant women that ingest dietary flavonoids affect their maternal thyroid function. In fact, those flavonoids inhibit the de-iodinases D2 or D3. Furthermore, the ingestion of plant isoflavonoids has many effects on the thyroid hormones and on the hypothalamus-pituitary axis. Therefore, besides viral or bacterial infections, dietary intake of pregnant women can also be the cause of autism in their children.
To think outside of the box, will mean asking questions like why doctors know the impact of those dietary intake and still give it to pregnant women?
http://www.jns-journal.com/article/S0022-510X(07)00437-6/fulltext
Your take on an alternative cause to autism disorder is interesting. However, the fact that there is a link between the maternal consumption of flavonoids during pregnancy puts the fetus at risk of developing autism does not overshadow the benefits brought on by them. It should be noted that the risk of autism caused by low thyroid hormone levels is prevalent during fetal neuronal migration, which happens to be during the first 8 – 12 weeks of development. So there is a small window in which the risk of the fetus developing autism is high. I guess they are so highly recommended in our diets by doctors because flavonoids possess antioxidative and other beneficial properties. I think the main concern is found in the concentration of flavonoid ingestion. I highly doubt that there is a damaging amount of flavonoids in foods that contain it, which is why the article you linked places a great emphasis on environmental components that contain flavonoids. If fact the average consumption of flavonoids is around 1 gram per day. There is evidence, however, that components of various flavonoids are capable of regulating different cellular processes including immune functions. This is not inherently a bad thing, it could reveal consequences if precautionary steps relating to diet are not taken.
http://link.springer.com/chapter/10.1007/978-1-4615-5335-9_13
http://www.sciencedirect.com/science/article/pii/0006295292904896
This article accurately describes the knowledge and research on Autism Spectrum Disorder (ASD)- diverse and challenging. The article mentions a study about mothers with viral or bacterial infections being more likely to have children that have ASD. The cytokine IL-17a seems to play a role in interfering with brain development of the fetus when the mother has been virally or bacterially infected. Instead of studying the complex mechanisms and causes of autism, a research was done on the mothers of autistic children. For example, the question of a research was did having autistic children cause the mother to have early causes of death? The study was completed just over a year ago in Australia and gathered data for over 20 years. The study by Fairthrone involved going through state-wide databases and information on the mother’s death after having a child with autism. Results showed that the mothers with autistic children showed more than twice the risk of death than mothers without autistic children. Moreover, mothers with autistic children were 50% more likely to die of cancer than non- autistic children mothers. This could possibly connect to the mother being so stressed about their autistic child, and it cause heart disease or cancer as mentioned by Ltran. It was very interesting to see the health side effects that autism can inflect not just the child, but the mother as well. Another path studies could take is if having an autistic child effects other siblings, or maybe even the father as well. Researchers could follow the same outline, and look at early death causes of fathers to compare the results to the mothers of autistic children.
Reference
http://www-ncbi-nlm-nih-gov.ezproxy.gsu.edu/pubmed/25535971
Despite the logic behind viral infections, bacterial infections and genetic makeup affecting the brain development of children that could potentially cause autism spectrum disorder (ASD), I believe is it essential to take all potential contributors into account when attempting to design a strategy to prevent autism development in children. With that being said, it is very important to take environmental factors into account. For instance, while the above study conducted on children born in Denmark between 1980 and 2005 highlighted an association between women suffering an infection sufficiently severe to require hospitalization and the ASD in their offspring, we must be hesitant to generalize this conclusion to the rest of the world. This is because an outbreak that could have spread through Denmark at the time could have been associated with an outbreak specific to its location that may not be an issue on another part of the world. For instance, pathogenic Leptospira bacteria invaded Denmark from 1980 to 2012 via sewage waters in Copenhagen, Denmark. The bacteria were recycled back into the environment via urine and had the ability to survive fresh water and warm and humid conditions. The study shown above is specific to an area at a certain time where poor sewage disposal was an immense problem that led to the severity of the disease and in turn a high percentage of offspring suffering of ASD. However, if you look to the other side of the world, Iraqi newborns are also facing defects in brain development post the war between the United States and Iraq. Countless numbers of children are now being born year later from mothers who became vulnerable to war pollution and toxins like uranium, titanium, lead and magnesium that are now leading to abnormal sensory, motor and cognitive functions in fetuses and young children. However if you take a look at the United States, poor sanitation conditions and war pollution in the United States are not a predominant problem. According to the CDC 1 in 68 children are diagnosed with ASD in the United States. The CDC also reported that ASD is five times more common among boys. How? Why is ASD more common in boys than girls? Perhaps it could potentially be more of a problem in genetic makeup or our continuous exposure to radiation through our famous microwavable meals or exaggerated cell phone use. For this reason, it is important to understand that there are a variety of factors that contribute to the development of ASD and it is essential to attempt to tackle all sides of the problem.
http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=21019
https://environment.yale.edu/yer/article/effects-of-war-pollution-on-iraqi-children-neurodevelopmental-disorders-and-birth-defects
The article discusses the correlation between pregnant women who develop serious infections while pregnant and the likelihood of these women producing a child with autism. Research was done using mice as models. The hypothesis tested was if a mother produces th17 while pregnant, the fetus will develop a brain disorder called Autism, however, if this formation of th17 is blocked by an antibody the brain disorder will not occur. The mice were either exposed to infection or stopped the formation of Th17 in the immune system using an antibody. The studies showed that when TH17 was blocked before inflammation by the antibody mouse fetus did not develop autism.
In the article, Autism Speaks, the author agrees with Shifter, author of Inflammation During Pregnanc: Links to Autism Development in the Offspring, stating that the activation of a female’s immune system during pregnancy causes inflammation which is a risk factor for autism. In this study mice or injected with the influenza infection caused high levels of MHC1 which negatively impacted brain cell development. Parallel to the experiment discussed above, when the MHC1 molecules were blocked normal brain development was observed. Still after various experimentation there is still uncertainty as to why the inflammation should cause changes in the brain? I ask the same question and also wonder to what strains must the infection be to cause inflammation?
References
https://www.autismspeaks.org/science/science-news/viral-inflammation-during-pregnancy-disrupts-brain-cell-connections
http://immunitytales.com/inflammation-during-pregnancy-links-to-autism-development-in-the-offspring/
In the article “Inflammation During Pregnancy: Links to Autism Development in the Offspring”, links between autism and immune system alterations mediated by pathogenic infection during early embryonic brain development were established. The researchers subjected the mice to double-stranded RNA, a molecule which mimics a viral infection, and observed an inflammatory response which prompted immune cells to secrete a cytokine, IL-17. Within the same mouse model, the researchers also revealed that exposure to this cytokine increased the amount of IL-17 receptors on the cells surface, thus increasing the sensitivity to inflammatory stimuli. Blockage of IL-17 production within the experimental model was shown to decrease abnormalities within the layer of the cerebral cortex of the mice, a defect believed to be linked to autism. The authors go on to suggest focusing research into the association between genetics and autism, however, I think it would be interesting to study, in detail, the effects of gestational diabetes and the development of autism.
Diabetes is a very prevalent disease that is increasing in our society. Could this increase in diabetes be associated with the observed increase in autism? One study (“The Association of Maternal Obesity and Diabetes With Autism and Other Developmental Disabilities.”) in the journal of Pediatrics suggests an increased risk of autism associated with obesity and pregestatentional diabetes. In particular, this study only evaluated the risk between diabetes and autism on a macro scale, finding a positive correlation. In contrast, I think it would be interesting to evaluate the link between molecular inflammatory complications seen within patients with diabetes and its relation to the immune system and embryonic development of autism.
Li M, Fallin MD, Riley A, Landa R, Walker SO, Silverstein M, Caruso D, Pearson C, Kiang S, Dahm JL, Hong X, Wang G, Wang MC, Zuckerman B, Wang X. “The Association of Maternal Obesity and Diabetes With Autism and Other Developmental Disabilities.” Pediatrics. (2016). 137(2):1-10. doi: 10.1542/peds.2015-2206.