2016 CDC Autism Prevalence – 1 in 68

U.S. Autism Rate Unchanged in New CDC Report


Researchers say it’s too early to tell if rate has stabilized

Researchers at the Johns Hopkins Bloomberg School of Public Health contributed to a new U.S. Centers for Disease Control and Prevention (CDC) report that finds the prevalence of autism spectrum disorder (ASD) largely unchanged from two years ago, at one in 68 children (or 1.46 percent). Boys were 4.5 times more likely to be identified with ASD than girls, an established trend. The rate is one in 42 among boys and one in 189 among girls.

ASD is a developmental disorder characterized by social and communication impairments, limited interest and repetitive behaviors. Early diagnosis and intervention are important to improving learning and skills. Rates have been rising since the 1960s, but researchers do not know how much of this rise is due to more children being diagnosed with ASD or if actual cases are increasing or a combination of both. The CDC’s first prevalance report, which was released in 2007 and was based on 2000 and 2002 data, found that one in 150 children had ASD.  

For this new report, the CDC collected data at 11 regional monitoring sites that are part of the Autism and Developmental Disabilities Monitoring (ADDM) Network in the following states: Arkansas, Arizona, Colorado, Georgia, Maryland, Missouri, New Jersey, North Carolina, South Carolina, Utah, and Wisconsin. The Maryland monitoring site is based at the Johns Hopkins Bloomberg School of Public Health.

“Although we did not observe a significant increase in the overall prevalence rates in the monitoring sites, we continue to see the disparity among racial and ethnic groups,” says Dr. Li-Ching Lee, PhD, ScM, a psychiatric epidemiologist with the Bloomberg School’s departments of Epidemiology and Mental Health, and the principal investigator for the Maryland-ADDM.  “For example, in Maryland, we found that Hispanic children were less likely to be evaluated for developmental concerns and therefore less likely to be identified.”

In Maryland, Lee notes, the vast majority of children (95 percent) identified with ASD had a developmental concern in their records by age three, but only 55 percent of them received a comprehensive evaluation by age three. “This lag may delay the timing for children with ASD to get diagnosed and receive needed services,” Lee says.

The prevalence in Maryland was one in 55 children (1.82 percent) with one in 34 among boys and one in 161 among girls. The data were derived from health and special education records of children who were eight years old and living in Baltimore County in 2012.

This is the sixth report by the CDC’s Autism and Developmental Disabilities Monitoring Network (ADDM), which has used the same surveillance methods for more than a decade.  Estimated prevalence rates of ASD in the U.S. reported by previous data were:

  • one in 68 children in the 2014 report that looked at 2010 data
  • one in 88 children in the 2012 report that looked at 2008 data
  • one in 110 children in the 2009 report that looked at 2006 data
  • one in 150 children in the 2007 report that looked at 2000 and 2002 data

The researchers say it is too early to tell if the overall prevalence rate has stabilized because the numbers vary widely across ADDM communities. In communities where both health and education records were reviewed, the rates are from a low of 1.24% in parts of South Carolina to a high of 2.46% in parts of New Jersey. 

Some trends in the latest CDC report data remain consistent, such as the greater likelihood of boys being diagnosed with ASD. Disparities by race/ethnicity in estimated ASD prevalence, the age of earliest comprehensive evaluation and presence of a previous ASD diagnosis or classification persist. Specifically, non-white children with ASD are being identified and evaluated at a later age than non-Hispanic white children.  The majority of children identified with ASD by the ADDM Network (82 percent) had a previous ASD diagnosis or a special educational classification.

The causes of autism are not completely understood; studies show that both environment and genetics may play a role. There is no known cure, and no treatment or intervention has been proven to reduce the prevalence of ASD. The CDC recommends that parents track their child’s development,  act quickly and get their child screened if they have a concern. Free checklists and information for parents, physicians and child care providers are available at http://www.cdc.gov/ActEarly.

A full copy of the report, “Prevalence of Autism Spectrum Disorder – Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2012,” is available on the CDC website here.

A copy of the Community Report with individual state statistics is available here.


Further Readings of Interest



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Environmental Enrichment as a Treatment for Early Life Inflammation

Environmental enrichment rescues the effects of early life inflammation on markers of synaptic transmission and plasticity.



Environmental enrichment (EE) has been successful at rescuing the brain from a variety of early-life psychogenic stressors.

However, its ability to reverse the behavioral and neural alterations induced by a prenatal maternal infection model of schizophrenia is less clear. Moreover, the specific interactions between the components (i.e. social enhancement, novelty, physical activity) of EE that lead to its success as a supportive intervention have not been adequately identified.

In the current study, standard housed female Sprague-Dawley rats were administered either the inflammatory endotoxin lipopolysaccharide (LPS; 100μg/kg) or pyrogen-free saline (equivolume) on gestational day 15.

On postnatal day 50, offspring were randomized into one of three conditions: EE (group housed in a large multi-level cage with novel toys, tubes and ramps), Colony Nesting (CN; socially-housed in a larger style cage), or Standard Care (SC; pair-housed in standard cages).

Six weeks later we scored social engagement and performance in the object-in-place task. Afterwards hippocampus and prefrontal cortex (n=7-9) were collected and evaluated for excitatory amino acid transporter (EAAT) 1-3, brain-derived neurotrophic factor (BDNF), and neurotrophic tyrosine kinase, receptor type 2 (TrkB) gene expression (normalized to GAPDH) using qPCR methods.

Overall, we show that gestational inflammation downregulates genes critical to synaptic transmission and plasticity, which may underlie the pathogenesis of neurodevelopmental disorders such as schizophrenia and autism. Additionally, we observed disruptions in both social engagement and spatial discrimination. Importantly, behavioral and neurophysiological effects were rescued in an experience dependent manner. Given the evidence that schizophrenia and autism may be associated with infection during pregnancy, these data have compelling implications for the prevention and reversibility of the consequences that follow immune activation in early in life.

Copyright © 2016 Elsevier Inc. All rights reserved.


Further Readings of Interest



Environmental Enrichment



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Microglia, Inflammation, the Immune System, Cerebral Palsy and Autism

Microglial migration and interactions with dendrimer nanoparticles are altered in the presence of neuroinflammation.




Microglial cells have been implicated in neuroinflammation-mediated injury in the brain, including neurodevelopmental disorders such as cerebral palsy (CP) and autism. Pro-inflammatory activation of microglial cells results in the impairment of their neuroprotective functions, leading to an exaggerated, ongoing immune dysregulation that can persist long after the initial insult. We have previously shown that dendrimer-mediated delivery of an anti-inflammatory agent can attenuate inflammation in a rabbit model of maternal inflammation-induced CP and significantly improve the motor phenotype, due to the ability of the dendrimer to selectively localize in activated microglia.


To elucidate the interactions between dendrimers and microglia, we created an organotypic whole-hemisphere brain slice culture model from newborn rabbits with and without exposure to inflammation in utero. We then used this model to analyze the dynamics of microglial migration and their interactions with dendrimers in the presence of neuroinflammation.


Microglial cells in animals with CP had an amoeboid morphology and impaired cell migration, demonstrated by decreased migration distance and velocity when compared to cells in healthy, age-matched controls. However, this decreased migration was associated with a greater, more rapid dendrimer uptake compared to microglial cells from healthy controls.


This study demonstrates that maternal intrauterine inflammation is associated with impaired microglial function and movement in the newborn brain. This microglial impairment may play a role in the development of ongoing brain injury and CP in the offspring. Increased uptake of dendrimers by the “impaired” microglia can be exploited to deliver drugs specifically to these cells and modulate their functions. Host tissue and target cell characteristics are important aspects to be considered in the design and evaluation of targeted dendrimer-based nanotherapeutics for improved and sustained efficacy. This ex vivo model also provides a rapid screening tool for evaluation of the effects of various therapies on microglial function.


Further Readings of Interest






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New Shift in Understanding – We are all Autism

Autism genes are in all of us, new research reveals


New light has been shed on the genetic relationship between autistic spectrum disorders (ASD) and ASD-related traits in the wider population, by a team of international researchers including academics from the University of Bristol, the Broad Institute of Harvard and MIT, and Massachusetts General Hospital (MGH).

The researchers studied whether there is a genetic relationship between ASD and the expression of ASD-related traits in populations not considered to have ASD. Their findings, published this week in Nature Genetics, suggest that genetic risk underlying ASD, including both inherited variants and de novo influences (not seen in an individual’s parents), affects a range of behavioural and developmental traits across the population, with those diagnosed with ASD representing a severe presentation of those traits.

Autism spectrum disorders (ASD) are a class of neurodevelopmental conditions affecting about 1 in 100 children. They are characterised by social interaction difficulties, communication and language impairments, as well as stereotyped and repetitive behaviour. These core symptoms are central to the definition of an ASD diagnosis but also occur, to varying degrees, in unaffected individuals and form an underlying behavioural continuum.

With recent advances in genome sequencing and analysis, a picture of ASD’s genetic landscape has started to take shape. Research has shown that most ASD risk is polygenic (stemming from the combined small effects of thousands of genetic differences, distributed across the genome). Some cases are also associated with rare genetic variants of large effect, which are usually de novo.

“There has been a lot of strong but indirect evidence that has suggested these findings,” said Dr Mark Daly, co-director of the Broad Institute’s Medical and Population Genetics (MPG) Program and senior author of the study.

“Once we had measurable genetic signals in hand – both polygenic risk and specific de novo mutations known to contribute to ASD – we were able to make an incontrovertible case that the genetic risk contributing to autism is genetic risk that exists in all of us, and influences our behaviour and social communication.”

Study co-first author Dr Elise Robinson, from MGH, said: “We can use behavioural and cognitive data in the general population to untangle the mechanisms through which different types of genetic risk are operating. We now have a better path forward in terms of expecting what types of disorders and traits are going to be associated with certain types of genetic risk.”

“Our study shows that collecting and using phenotypic and genetic data in typically developing children can be useful in terms of the design and interpretation of studies targeting complex neurodevelopmental and psychiatric disorders,” said study co-first author Dr Beate St Pourcain, from the Medical Research Council Integrative Epidemiology Unit at the University of Bristol and the Max Planck Institute for Psycholinguistics.

“Based on the genetic link between population-based social-communication difficulties and clinical ASD, we may now gain further phenotypic insight into a defined set of genetically-influenced ASD symptoms. This may help us to identify and investigate biological processes in typically-developing children, which are disturbed in children with ASD.”

The data on unaffected individuals came from a general population cohort (the Bristol-based Avon Longitudinal Study of Parents and Children) and a nuclear family cohort (the Simons Simplex Collection) of ASD cases and unaffected siblings; ASD collections included several large, international autism genetic studies: the Psychiatric Genomics Consortium Autism group, the iPSYCH autism project in Denmark, the SSC, and the Autism Sequencing Consortium.

Professor George Davey Smith, co-author and scientific director of ALSPAC, said: “Many traits that related to disease risk – like blood pressure or cholesterol levels – demonstrate a similar continuum of risk, with contributions from common and rare genetic variants, plus environmental and chance events. The present study demonstrates how this continuum applies to a condition generally thought of as either existing or not.”

The researchers expect the approach to be used to explore the associations between genetic risk and behavioural traits in other neuropsychiatric disorders such as schizophrenia in the future.


‘Genetic risk for autism spectrum disorders and neuropsychiatric variation in the general population’ by Robinson, EB, St. Pourcain, B et al in Nature Genetics. Online March 21, 2016

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Immune Response and Complement system play a Major role in Epilepsy

Identification of novel gene and pathway targets for human epilepsy treatment.




The aim of this study was to explore epilepsy-related mechanism so as to figure out the possible targets for epilepsy treatment.


The gene expression profile dataset GES32534 was downloaded from Gene Expression Omnibus database. We identified the differentially expressed genes (DEGs) by Affy package. Then the DEGs were used to perform gene ontology (GO) and pathway enrichment analyses. Furthermore, a protein-protein interaction (PPI) network was constructed with the DEGs followed by co-expression modules construction and analysis.


Total 420 DEGs were screened out, including 214 up-regulated and 206 down-regulated genes. Functional enrichment analysis revealed that down-regulated genes were mainly involved in the process of immunity regulation and biological repairing process while up-regulated genes were closely related to transporter activity. PPI network analysis showed the top ten genes with high degrees were all down-regulated, among which FN1 had the highest degree. The up-regulated and down-regulated DEGs in the PPI network generated two obvious sub-co-expression modules, respectively. In up-co-expression module, SCN3B (sodium channel, voltage gated, type III beta subunit) was enriched in GO:0006814 ~ sodium ion transport. In down-co-expression module, C1QB (complement C1s), C1S (complement component 1, S subcomponent) and CFI (complement factor I) were enriched in GO:0006955 ~ immune response.


The immune response and complement system play a major role in the pathogenesis of epilepsy. Additionally, C1QB, C1S, CFI, SCN3B and FN1 may be potential therapeutic targets for epilepsy.


Further Readings of Interest




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Inflammatory Pathways in Epilepsy

Inflammatory mediators in human epilepsy: A systematic review and meta-analysis.




Accumulating evidence suggests a role for inflammation in the pathophysiology of epilepsy.


We performed a systematic review and meta-analysis of studies that investigated inflammatory mediators in human epilepsy. Studies reporting on inflammatory mediators in serum, cerebrospinal fluid or brain tissue of epilepsy patients were included. Studies comparing patients to controls were included in a meta-analysis.


66 articles reporting on 1934 patients were included. IL-1ra, IL-1β, IL-6, IL-10, IFN-γ and TNF-α were the most extensively investigated proteins. Elevated levels for IL-1ra, IL-1β, IL-6 and CXCL8/IL-8 were reported in several different epilepsy etiologies and media, while other proteins were specifically increased for one etiology. IL-1α, IL-7 and IL-13, as well as the chemokines CCL2-5, -19 and -22, were increased exclusively in brain tissue. In an aggregate meta-analysis, we found significantly different protein levels for serum IL-6, IL-17 and CSF IL-1β and IL-10.


Inflammatory pathways are involved in epilepsy. Future studies may further clarify their role, and prove potential of targeted anti-inflammatory treatment.

Copyright © 2016 Elsevier Ltd. All rights reserved.


Further Readings of Interest




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Autism co-morbidity in Epilepsy – New Spanish Research

Prognosis of symptomatic epilepsies in relation to their age of onset, monitored at a neuropediatric section of regional reference over a period of three years].



To analyze the factors involved in the prognosis of symptomatic epilepsies in relation to their age at onset, monitored at a neuropediatric section of regional reference over a period of three years.


Children diagnosed with symptomatic epilepsy, supervised from January 1, 2008 to December 31, 2010, collecting epidemiological, clinical and developmental data.


Of the 4595 children attended during the period, the diagnosis of epilepsy was established at 605 (13.17%): 277 (45.79%) symptomatic epilepsies. Symptomatic etiology predomininates in epileptic patients that started below one year of age, 67.72%, and between 1-3 years, 61.39%. 37.54% of symptomatic epilepsy is refractory, 72.92% have cognitive impairment, 55.23% have motor impairment and 17.32% have autism spectrum disorder. The younger the patient, the higher the percentage of refractoriness and display of any neurological or associated development impact. Some etiologies have higher rates of refractoriness.


A useful classification would be etiological, with two groups: a large group with established etiology or very likely genetic syndromes and another with no established cause. The age of onset of epilepsy in each etiological group adds prognostic orientation. Prognosis of epilepsy is overshadowed by refractoriness and associated neurodevelopmental disorders, which are generally worse at an earlier onset and in certain etiologies.


Further Readings of Interest


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Breakthrough – Autism, Immune Cells and Pruning

The Brain’s Gardeners: Immune Cells ‘Prune’ Connections Between Neurons


A new study out today in the journal Nature Communications shows that cells normally associated with protecting the brain from infection and injury also play an important role in rewiring the connections between nerve cells.  While this discovery sheds new light on the mechanics of neuroplasticity, it could also help explain diseases like autism spectrum disorders, schizophrenia, and dementia, which may arise when this process breaks down and connections between brain cells are not formed or removed correctly.

“We have long considered the reorganization of the brain’s network of connections as solely the domain of neurons,” said Ania Majewska, Ph.D., an associate professor in the Department of Neuroscience at the University of Rochester Medical Center (URMC) and senior author of the study.  “These findings show that a precisely choreographed interaction between multiple cells types is necessary to carry out the formation and destruction of connections that allow proper signaling in the brain.”

The study is another example of a dramatic shift in scientists’ understanding of the role that the immune system, specifically cells called microglia, plays in maintaining brain function.  Microglia have been long understood to be the sentinels of the central nervous system, patrolling the brain and spinal cord and springing into action to stamp out infections or gobble up dead cell tissue.  However, scientists are now beginning to appreciate that, in addition to serving as the brain’s first line of defense, these cells also have a nurturing side, particularly as it relates to the connections between neurons.

The formation and removal of the physical connections between neurons is a critical part of maintaining a healthy brain and the process of creating new pathways and networks among brain cells enables us to absorb, learn, and memorize new information.

“The brain’s network of connections is like a garden,” said Rebecca Lowery, a graduate student in Majewska’s lab and co-author of the study.  “Not only does it require nourishment and a healthy environment, but every once in a while you need to prune dead branches and pull up weeds in order to allow new flowers to grow.”

While this constant reorganization of neural networks – called neuroplasticity – has been well understood for some time, the basic mechanisms by which connections between brain cells are made and broken has eluded scientists.

Performing experiments in mice, the researchers employed a well-established model of measuring neuroplasticity by observing how cells reorganize their connections when visual information received by the brain is reduced from two eyes to one.

The researchers found that in the mice’s brains microglia responded rapidly to changes in neuronal activity as the brain adapted to processing information from only one eye.  They observed that the microglia targeted the synaptic cleft – the business end of the connection that transmits signals between neurons.  The microglia “pulled up” the appropriate connections, physically disconnecting one neuron from another, while leaving other important connections intact.

This is similar to what occurs during an infection or injury, in which microglia are activated, quickly navigate towards the injured site, and remove dead or diseased tissue while leaving healthy tissue untouched. 

The researchers also pinpointed one of the key molecular mechanisms in this process and observed that when a single receptor – called P2Y12 – was turned off the microglia ceased removing the connections between neurons.

These findings may provide new insight into disorders that are the characterized by sensory or cognitive dysfunction, such as autism spectrum disorders, schizophrenia, and dementia.  It is possible that when the microglia’s synapse pruning function is interrupted or when the cells mistakenly remove the wrong connections – perhaps due to genetic factors or because the cells are too occupied elsewhere fighting an infection or injury – the result is impaired signaling between brain cells.

“These findings demonstrate that microglia are a dynamic and integral component of the complex machinery that allows neurons to reorganize their connections in the healthy mature brain,” said Grayson Sipe, a graduate student in Majewska’s lab and co-author of the study.  “While more work needs to be done to fully understand this process, this study may help us understand how genetics or disruption of the immune system contributes to neurological disorders.”

Additional co-authors include Emily Kelly and Cassandra Lamantia with URMC and Marie Eve Tremblay with Laval University in Quebec.  The study was support by the National Eye Institute and the National Institute for Neurological Disorders and Stroke.

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Maternal Care – Key to Autism

Obesity, Diabetes in Mom Increases Risk of Autism in Child


New study offers new evidence that autism spectrum disorder risks may begin in utero

Children born to obese women with diabetes are more than four times as likely to be diagnosed with autism spectrum disorder than children of healthy weight mothers without diabetes, new Johns Hopkins Bloomberg School of Public Health research suggests.

The findings, to be published Jan. 29 in the journal Pediatrics, highlight what has become a leading theory about autism, that the risk likely develops before the child is even born.

“We have long known that obesity and diabetes aren’t good for mothers’ own health,” says study leader Xiaobin Wang, MD, ScD, MPH, the Zanvyl Krieger Professor in Child Health at the Bloomberg School and director of the Center on the Early Life Origins of Disease. “Now we have further evidence that these conditions also impact the long-term neural development of their children.”

Autism spectrum disorder is a neurodevelopmental condition characterized by severe deficits in socialization, verbal and nonverbal communication and repetitive behaviors. Since the 1960s, the prevalence rates have skyrocketed, with one in 68 U.S. children now affected by it, according to the U.S. Centers for Disease Control and Prevention. Obesity and diabetes have also risen to epidemic levels in women of reproductive age over the same time period.

For the study, the researchers analyzed 2,734 mother-child pairs, a subset of the Boston Birth Cohort recruited at the Boston Medical Center at birth between 1998 and 2014. They collected data on maternal pre-pregnancy weight and whether the mothers had diabetes before getting pregnant or whether they developed gestational diabetes during pregnancy. They also followed up the children from birth through childhood via postnatal study visits and review of electronic medical records. They identified 102 children who were diagnosed with autism spectrum disorder over the course of the study. Those children with mothers who were both diabetic and obese were more than four times as likely to develop autism compared to children born to normal weight mothers without diabetes, they found.

“Our research highlights that the risk for autism begins in utero,” says co-author M. Daniele Fallin, PhD, chair of the Bloomberg School’s Department of Mental Health and director of the Wendy Klag Center for Autism and Developmental Disabilities. “It’s important for us to now try to figure out what is it about the combination of obesity and diabetes that is potentially contributing to sub-optimal fetal health.”

Previous studies had suggested a link between maternal diabetes and autism, but this is believed to be the first to look at obesity and diabetes in tandem as potential risk factors.

Along with pre-conception diabetes, children of obese mothers who developed gestational diabetes during pregnancy were also at a significantly higher risk of being diagnosed with autism.

The biology of why obesity and diabetes may contribute to autism risk isn’t well understood. Obesity and diabetes in general cause stress on the human body, the researchers say. Previous research suggests maternal obesity may be associated with an inflammation in the developing fetal brain. Other studies suggest obese women have less folate, a B-vitamin vital for  human development and health.

The researchers say that women of reproductive age who are thinking about having children need to not only think about their obesity and diabetes status for their own health, but because of the implications it could have on their children. Better diabetes and weight management could have lifelong impacts on mother and child, they say.

“In order to prevent autism, we may need to consider not only pregnancy, but also pre-pregnancy health,” Fallin says.

“The association of maternal obesity and diabetes with autism and other developmental disabilities” was written by Mengying Li; M. Daniele Fallin; Anne Riley; Rebecca Landa; Sheila O. Walker; Michael Silverstein; Deanna Caruso; Colleen Pearson; Shannon Kiang; Jamie Lyn Dahm; Xiumei Hong; Guoying Wang; Mei-Cheng Weng; Barry Zuckerman and Xiaobin Wang.

The parent study was supported in part by the March of Dimes, the National Institute of Environmental Health Sciences (R21 ES011666) and the National Institute of Child Health and Human Development (2R01 HD041702). The Pediatrics study is supported in part by the Ludwig Family Foundation; the National Institute of Allergy and Infectious Diseases (U01AI90727 and R21AI079872) and the Maternal and Child Health Bureau (R40MC27442).

Further Readings of Interest

Obesity and Autism


Diabetes and Autism


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A Mother’s Inflammation and Autism

How severe maternal inflammation can lead to autism-like behavior


Immune molecules in infected mothers tied to brain and behavior abnormalities in offspring.


Anne Trafton | MIT News Office
January 28, 2016


In 2010, a large study in Denmark found that women who suffered an infection severe enough to require hospitalization while pregnant were much more likely to have a child with autism (even though the overall risk of delivering a child with autism remained low).

Now research from MIT, the University of Massachusetts Medical School, the University of Colorado, and New York University Langone Medical Center reveals a possible mechanism for how this occurs. In a study of mice, the researchers found that immune cells activated in the mother during severe inflammation produce an immune effector molecule called IL-17 that appears to interfere with brain development.

The researchers also found that blocking this signal could restore normal behavior and brain structure.

“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,” says Gloria Choi, an assistant professor of brain and cognitive sciences, a member of MIT’s McGovern Institute for Brain Research, and the lead author of the study, which appears in the Jan. 28 online edition of Science.

Finding the link

In the 2010 study, which included all children born in Denmark between 1980 and 2005, severe infections (requiring hospitalization) that correlated with autism risk included influenza, viral gastroenteritis, and urinary tract infections. Severe viral infections during the first trimester translated to a threefold risk for autism, and serious bacterial infections during the second trimester were linked with a 1.5-fold increase in risk.

Choi and her husband, Jun Huh, were graduate students at Caltech when they first heard about this study during a lecture by Caltech professor emeritus Paul Patterson, who had discovered that an immune signaling molecule called IL-6 plays a role in the link between infection and autism-like behaviors in rodents.

Huh, now an assistant professor at the University of Massachusetts Medical School and one of the paper’s senior authors, was studying immune cells called Th17 cells, which are well known for contributing to autoimmune disorders such as multiple sclerosis, inflammatory bowel diseases, and rheumatoid arthritis. He knew that Th17 cells are activated by IL-6, so he wondered if these cells might also be involved in cases of animal models of autism associated with maternal infection.

“We wanted to find the link,” Choi says. “How do you go all the way from the immune system in the mother to the child’s brain?”

Choi and Huh launched the study as postdocs at Columbia University and New York University School of Medicine, respectively. Working with Dan Littman, a professor of molecular immunology at NYU and one of the paper’s senior authors, they injected pregnant mice with a synthetic analog of double-stranded RNA, which activates the immune system in a similar way to viruses.

Confirming the results of previous studies in mice, the researchers found behavioral abnormalities in the offspring of the infected mothers, including deficits in sociability, repetitive behaviors, and abnormal communication. They then disabled Th17 cells in the mothers before inducing inflammation and found that the offspring mice did not show those behavioral abnormalities. The abnormalities also disappeared when the researchers gave the infected mothers an antibody that blocks IL-17, which is produced by Th17 cells.

The researchers next asked how IL-17 might affect the developing fetus. They found that brain cells in the fetuses of mothers experiencing inflammation express receptors for IL-17, and they believe that exposure to the chemical provokes cells to produce even more receptors for IL-17, amplifying its effects.

In the developing mice, the researchers found irregularities in the normally well-defined layers of cells in the brain’s cortex, 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 the mothers’ Th17 cells were blocked.

Disorganized cortical layers have also been found in studies of human patients with autism.

Preventing autism

The researchers are now investigating whether and how these cortical patches produce the behavioral abnormalities seen in the offspring.

“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,” Choi says. “And if it is responsible, what is being dysregulated within this patch to produce this behavior?”

The researchers hope their work may lead to a way to reduce the chances of autism developing in the children of women who experience severe infections during pregnancy. They also plan to investigate whether genetic makeup influences mice’s susceptibility to maternal inflammation, because autism is known to have a very strong genetic component.

Charles Hoeffer, a professor of integrative physiology at the University of Colorado, is a senior author of the paper, and other authors include MIT postdoc Yeong Yim, NYU graduate student Helen Wong, UMass Medical School visiting scholars Sangdoo Kim and Hyunju Kim, and NYU postdoc Sangwon Kim.

Further Readings of Interest


Posted in Allergy, Asthma, Autism, Bacteria, bowel disease, co-morbid, Depression, diabetes, Environment, Epidemiology, Epigenetics, epilepsy, Gut, IBD, Immune System, Inflammation, influenza, Mice, Neurology, Parents, Toxins, Treatment, Virus | Leave a comment