Startling Discovery – Immune System Affects and may Control Social Behavior

Shocking New Role Found for the Immune System: Controlling Social Interactions

In a startling discovery that raises fundamental questions about human behavior, researchers at the University of Virginia School of Medicine have determined that the immune system directly affects – and even controls – creatures’ social behavior, such as their desire to interact with others.

So could immune system problems contribute to an inability to have normal social interactions? The answer appears to be yes, and that finding could have significant implications for neurological diseases such as autism-spectrum disorders and schizophrenia.

“The brain and the adaptive immune system were thought to be isolated from each other, and any immune activity in the brain was perceived as sign of a pathology. And now, not only are we showing that they are closely interacting, but some of our behavior traits might have evolved because of our immune response to pathogens,” explained Jonathan Kipnis, chair of UVA’s Department of Neuroscience. “It’s crazy, but maybe we are just multicellular battlefields for two ancient forces: pathogens and the immune system. Part of our personality may actually be dictated by the immune system.”

Evolutionary Forces at Work

It was only last year that Kipnis, the director of UVA’s Center for Brain Immunology and Glia, and his team discovered that meningeal vessels directly link the brain with the lymphatic system. That overturned decades of textbook teaching that the brain was “immune privileged,” lacking a direct connection to the immune system. The discovery opened the door for entirely new ways of thinking about how the brain and the immune system interact.

The follow-up finding is equally illuminating, shedding light on both the workings of the brain and on evolution itself. The relationship between people and pathogens, the researchers suggest, could have directly affected the development of our social behavior, allowing us to engage in the social interactions necessary for the survival of the species while developing ways for our immune systems to protect us from the diseases that accompany those interactions. Social behavior is, of course, in the interest of pathogens, as it allows them to spread.

The UVA researchers have shown that a specific immune molecule, interferon gamma, seems to be critical for social behavior and that a variety of creatures, such as flies, zebrafish, mice and rats, activate interferon gamma responses when they are social. Normally, this molecule is produced by the immune system in response to bacteria, viruses or parasites. Blocking the molecule in mice using genetic modification made regions of the brain hyperactive, causing the mice to become less social. Restoring the molecule restored the brain connectivity and behavior to normal. In a paper outlining their findings, the researchers note the immune molecule plays a “profound role in maintaining proper social function.”

“It’s extremely critical for an organism to be social for the survival of the species. It’s important for foraging, sexual reproduction, gathering, hunting,” said Anthony J. Filiano, Hartwell postdoctoral fellow in the Kipnis lab and lead author of the study. “So the hypothesis is that when organisms come together, you have a higher propensity to spread infection. So you need to be social, but [in doing so] you have a higher chance of spreading pathogens. The idea is that interferon gamma, in evolution, has been used as a more efficient way to both boost social behavior while boosting an anti-pathogen response.”

Understanding the Implications

The researchers note that a malfunctioning immune system may be responsible for “social deficits in numerous neurological and psychiatric disorders.” But exactly what this might mean for autism and other specific conditions requires further investigation. It is unlikely that any one molecule will be responsible for disease or the key to a cure. The researchers believe that the causes are likely to be much more complex. But the discovery that the immune system – and possibly germs, by extension – can control our interactions raises many exciting avenues for scientists to explore, both in terms of battling neurological disorders and understanding human behavior.

“Immune molecules are actually defining how the brain is functioning. So, what is the overall impact of the immune system on our brain development and function?” Kipnis said. “I think the philosophical aspects of this work are very interesting, but it also has potentially very important clinical implications.”

Findings Published

Kipnis and his team worked closely with UVA’s Department of Pharmacology and with Vladimir Litvak’s research group at the University of Massachusetts Medical School. Litvak’s team developed a computational approach to investigate the complex dialogue between immune signaling and brain function in health and disease.

“Using this approach we predicted a role for interferon gamma, an important cytokine secreted by T lymphocytes, in promoting social brain functions,” Litvak said. “Our findings contribute to a deeper understanding of social dysfunction in neurological disorders, such as autism and schizophrenia, and may open new avenues for therapeutic approaches.”

The findings have been published online by the prestigious journal Nature. The article was written by Filiano, Yang Xu, Nicholas J. Tustison, Rachel L. Marsh, Wendy Baker, Igor Smirnov, Christopher C. Overall, Sachin P. Gadani, Stephen D. Turner, Zhiping Weng, Sayeda Najamussahar Peerzade, Hao Chen, Kevin S. Lee, Michael M. Scott, Mark P. Beenhakker, Litvak and Kipnis.

This work was supported by the National Institutes of Health (grants No. AG034113, NS081026 and T32-AI007496) and the Hartwell Foundation.

Further Readings of Interest
Immune system and Autism
Posted in Allergy, Asthma, Autism, Bacteria, bowel disease, co-morbid, Environment, Gut, IBD, Immune System, Inflammation, influenza, Neurology, Physiology, Treatment, Virus | Leave a comment

Allergy, Inflammation and Autism

Atopic diseases and inflammation of the brain in the pathogenesis of autism spectrum disorders

Free Full Paper


Autism spectrum disorders (ASDs) affect as many as 1 in 45 children and are characterized by deficits in sociability and communication, as well as stereotypic movements.

Many children also show severe anxiety.

The lack of distinct pathogenesis and reliable biomarkers hampers the development of effective treatments. As a result, most children with ASD are prescribed psychopharmacologic agents that do not address the core symptoms of ASD.

Autoantibodies against brain epitopes in mothers of children with ASD and many such children strongly correlate with allergic symptoms and indicate an aberrant immune response, as well as disruption of the blood–brain barrier (BBB).

Recent epidemiological studies have shown a strong statistical correlation between risk for ASD and either maternal or infantile atopic diseases, such as asthma, eczema, food allergies and food intolerance, all of which involve activation of mast cells (MCs). These unique tissue immune cells are located perivascularly in all tissues, including the thalamus and hypothalamus, which regulate emotions. MC-derived inflammatory and vasoactive mediators increase BBB permeability. Expression of the inflammatory molecules interleukin (IL-1β), IL-6, 1 L-17 and tumor necrosis factor (TNF) is increased in the brain, cerebrospinal fluid and serum of some patients with ASD, while NF-kB is activated in brain samples and stimulated peripheral blood immune cells of other patients; however, these molecules are not specific. Instead the peptide neurotensin is uniquely elevated in the serum of children with ASD, as is corticotropin-releasing hormone, secreted from the hypothalamus under stress. Both peptides trigger MC to release IL-6 and TNF, which in turn, stimulate microglia proliferation and activation, leading to disruption of neuronal connectivity. MC-derived IL-6 and TGFβ induce maturation of Th17 cells and MCs also secrete IL-17, which is increased in ASD. Serum IL-6 and TNF may define an ASD subgroup that benefits most from treatment with the natural flavonoid luteolin.

Atopic diseases may create a phenotype susceptible to ASD and formulations targeting focal inflammation of the brain could have great promise in the treatment of ASD.


Further Readings of Interest

Allergy and Atopic

Posted in Allergy, Asthma, Autism, Bacteria, bowel disease, co-morbid, Depression, Environment, Gut, IBD, Immune System, Inflammation, Treatment | Leave a comment

The Gut, Microbes and Rheumatoid Arthritis

Study: Gut Bacteria can Cause, Predict and Prevent Rheumatoid Arthritis

ROCHESTER, Minn. — The bacteria in your gut do more than break down your food. They also can predict susceptibility to rheumatoid arthritis, suggests Veena Taneja, Ph.D., an immunologist at Mayo Clinic’s Center for Individualized Medicine. Dr. Taneja recently published two studies ─ one in Genome Medicine and one in Arthritis and Rheumatology ─ connecting the dots between gut microbiota and rheumatoid arthritis.

More than 1.5 million Americans have rheumatoid arthritis, a disorder that causes painful swelling in the joints. Scientists have a limited understanding of the processes that trigger the disease. Dr. Taneja and her team identified intestinal bacteria as a possible cause; their studies indicate that testing for specific microbiota in the gut can help physicians predict and prevent the onset of rheumatoid arthritis.

“These are exciting discoveries that we may be able to use to personalize treatment for patients,” Dr. Taneja says.

The paper published in Genome Medicine summarizes a study of rheumatoid arthritis patients, their relatives and a healthy control group. The study aimed to find a biomarker — or a substance that indicates a disease, condition or phenomena — that predicts susceptibility to rheumatoid arthritis. They noted that an abundance of certain rare bacterial lineages causes a microbial imbalance that is found in rheumatoid arthritis patients.

“Using genomic sequencing technology, we were able to pin down some gut microbes that were normally rare and of low abundance in healthy individuals, but expanded in patients with rheumatoid arthritis,” Dr. Taneja says.

Implications for predicting and preventing rheumatoid arthritis

After further research in mice and, eventually, humans, intestinal microbiota and metabolic signatures could help scientists build a predictive profile for who is likely to develop rheumatoid arthritis and the course the disease will take, Dr. Taneja says.

Based on mouse studies, researchers found an association between the gut microbe Collinsella and the arthritis phenotype. The presence of these bacteria may lead to new ways to diagnose patients and to reduce the imbalance that causes rheumatoid arthritis before or in its early stages, according to John Davis III, M.D., and Eric Matteson, M.D., Mayo Clinic rheumatologists and study co-authors. Continued research could lead to preventive treatments.

Possibility for more effective treatment with fewer side effects

The second paper, published in Arthritis and Rheumatology, explored another facet of gut bacteria. Dr. Taneja treated one group of arthritis-susceptible mice with a bacterium, Prevotella histicola, and compared that to a group that had no treatment. The study found that mice treated with the bacterium had decreased symptom frequency and severity, and fewer inflammatory conditions associated with rheumatoid arthritis. The treatment produced fewer side effects, such as weight gain and villous atrophy — a condition that prevents the gut from absorbing nutrients — that may be linked with other, more traditional  treatments.

While human trials have not yet taken place, the mice’s immune systems and arthritis mimic humans, and shows promise for similar, positive effects. Since this bacterium is a part of healthy human gut, treatment is less likely to have side effects, says study co-author Joseph Murray, M.D., a Mayo Clinic gastroenterologist.

Rheumatoid arthritis is an autoimmune disorder; it occurs when the body mistakenly attacks itself. The body breaks down tissues around joints, causing swelling that can erode bone and deform the joints. The disease can damage other parts of the body, including the skin, eyes, heart, lung and blood vessels.

The study was funded by the Mayo Clinic Center for Individualized Medicine, which supports research that aims to find treatments compatible with a patient’s unique genetic structure. It also supports the transformation of research discoveries into practical applications for patient care.

MEDIA CONTACT: Colette Rector, Mayo Clinic Public Affairs, 507-284-5005,


About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to clinical practice, education and research, providing expert, whole-person care to everyone who needs healing. For more information, visit or

Further Readings of Interest




Posted in Autism, Bacteria, bowel disease, co-morbid, Environment, Gut, IBD, Immune System, Inflammation, Mice, Treatment | Leave a comment

The Gut, Microbes and MS

Changes Uncovered in the Gut Bacteria of Patients with Multiple Sclerosis

A connection between the bacteria living in the gut and immunological disorders such as multiple sclerosis have long been suspected, but for the first time, researchers have detected clear evidence of changes that tie the two together. Investigators from Brigham and Women’s Hospital (BWH) have found that people with multiple sclerosis have different patterns of gut microorganisms than those of their healthy counterparts. In addition, patients receiving treatment for MS have different patterns than untreated patients. The new research, published in Nature Communications, supports recent studies linking immunological disorders to the gut microbiome and may have implications for pursuing new therapies for MS.

“Our findings raise the possibility that by affecting the gut microbiome, one could come up with treatments for MS – treatments that affect the microbiome, and, in turn, the immune response,” said Howard L. Weiner, MD, director of the Partners MS Center and co-director of the Ann Romney Center for Neurologic Disease at Brigham Women’s Hospital, . “There are a number of ways that the microbiome could play a role in MS and this opens up a whole new world of looking at the disease in a way that it’s never been looked at before.”

Weiner and colleagues conducted their investigations using data and samples from subjects who are part of the CLIMB (Comprehensive Longitudinal Investigation of Multiple Sclerosis) study at Brigham and Women’s Hospital. The team analyzed stool samples from 60 people with MS and 43 control subjects, performing gene sequencing to detect differences in the microbial communities of the subjects.

Samples from MS patients contained higher levels of certain bacterial species – including Methanobrevibacter and Akkermansia – and lower levels of others – such as Butyricimonas – when compared to healthy samples. Other studies have found that several of these microorganisms may drive inflammation or are associated with autoimmunity. Importantly, the team also found that microbial changes in the gut correlated with changes in the activity of genes that play a role in the immune system. The team also collected breath samples from subjects, finding that, as a result of increased levels of Methanobrevibacter, patients with MS had higher levels of methane in their breath samples.

The researchers also investigated the gut microbe communities of untreated MS patients, finding that MS disease-modifying therapy appeared to normalize the gut microbiomes of MS patients. The researchers note that further study will be required to determine the exact role that these microbes may be playing in the progression of disease and whether or not modifying the microbiome may be helpful in treating MS. They plan to continue to explore the connection between the gut and the immune system in a larger group of patients and follow changes over time to better understand disease progression and interventions.

“This work provides a window into how the gut can affect the immune system which can then affect the brain,” said Weiner, who is also a professor of Neurology at Harvard Medical School. “Characterizing the gut microbiome in those with MS may provide new opportunities to diagnose MS and point us toward new interventions to help prevent disease development in those who are at risk.”

Funding support for this work included grants from the NIH/NINDS, The National Multiple Sclerosis Society and from The Harvard Digestive Disease Center.

Paper cited: Jangi S et al. “Alterations of the human gut microbiome in multiple sclerosis.” Nature Communications. DOI: 10.1038/NCOMMS12015



Posted in co-morbid, Environment, Gut, IBD, Immune System, Inflammation, Uncategorized | Leave a comment

Neuropathology of Seizures in Autism

Neuropathological Mechanisms of Seizures in Autism Spectrum Disorder.


This manuscript reviews biological abnormalities shared by autism spectrum disorder (ASD) and epilepsy.

Two neuropathological findings are shared by ASD and epilepsy:

abnormalities in minicolumn architecture and

γ-aminobutyric acid (GABA) neurotransmission.

The peripheral neuropil, which is the region that contains the inhibition circuits of the minicolumns, has been found to be decreased in the post-mortem ASD brain. ASD and epilepsy are associated with inhibitory GABA neurotransmission abnormalities including reduced GABAA and GABAB subunit expression. These abnormalities can elevate the excitation-to-inhibition balance, resulting in hyperexcitablity of the cortex and, in turn, increase the risk of seizures.

Medical abnormalities associated with both epilepsy and ASD are discussed. These include specific genetic syndromes, specific metabolic disorders including disorders of energy metabolism and GABA and glutamate neurotransmission, mineral and vitamin deficiencies, heavy metal exposures and immune dysfunction.

Many of these medical abnormalities can result in an elevation of the excitatory-to-inhibitory balance. Fragile X is linked to dysfunction of the mGluR5 receptor and Fragile X, Angelman and Rett syndromes are linked to a reduction in GABAA receptor expression. Defects in energy metabolism can reduce GABA interneuron function. Both pyridoxine dependent seizures and succinic semialdehyde dehydrogenase deficiency cause GABA deficiencies while urea cycle defects and phenylketonuria cause abnormalities in glutamate neurotransmission. Mineral deficiencies can cause glutamate and GABA neurotransmission abnormalities and heavy metals can cause mitochondrial dysfunction which disrupts GABA metabolism.

Thus, both ASD and epilepsy are associated with similar abnormalities that may alter the excitatory-to-inhibitory balance of the cortex. These parallels may explain the high prevalence of epilepsy in ASD and the elevated prevalence of ASD features in individuals with epilepsy.

Other Readings of Interest


Epilepsy and Autism

Posted in Autism, co-morbid, epilepsy, Immune System, Treatment | Leave a comment

Immune System, Epilepsy and the Eye

Immune response in the eye following epileptic seizures




Epileptic seizures are associated with an immune response in the brain. However, it is not known whether it can extend to remote areas of the brain, such as the eyes. Hence, we investigated whether epileptic seizures induce inflammation in the retina.


Adult rats underwent electrically induced temporal status epilepticus, and the eyes were studied 6 h, 1, and 7 weeks later with biochemical and immunohistochemical analyses. An additional group of animals received CX3CR1 antibody intracerebroventricularly for 6 weeks after status epilepticus.


Biochemical analyses and immunohistochemistry revealed no increased cell death and unaltered expression of several immune-related cytokines and chemokines as well as no microglial activation, 6 h post-status epilepticus compared to non-stimulated controls. At 1 week, again, retinal cytoarchitecture appeared normal and there was no cell death or micro- or macroglial reaction, apart from a small decrease in interleukin-10. However, at 7 weeks, even if the cytoarchitecture remained normal and no ongoing cell death was detected, the numbers of microglia were increased ipsi- and contralateral to the epileptic focus. The microglia remained within the synaptic layers but often in clusters and with more processes extending into the outer nuclear layer. Morphological analyses revealed a decrease in surveying and an increase in activated microglia. In addition, increased levels of the chemokine KC/GRO and cytokine interleukin-1β were found. Furthermore, macroglial activation was noted in the inner retina. No alterations in numbers of phagocytic cells, infiltrating macrophages, or vascular pericytes were observed. Post-synaptic density-95 cluster intensity was reduced in the outer nuclear layer, reflecting seizure-induced synaptic changes without disrupted cytoarchitecture in areas with increased microglial activation. The retinal gliosis was decreased by a CX3CR1 immune modulation known to reduce gliosis within epileptic foci, suggesting a common immunological reaction.


Our results are the first evidence that epileptic seizures induce an immune response in the retina. It has a potential to become a novel non-invasive tool for detecting brain inflammation through the eyes.

Posted in Autism, co-morbid, epilepsy, Immune System, Inflammation | Leave a comment

Hygiene Hypothesis and The Gut.

The gut microbiomes of infants have an impact on autoimmunity

Exposure to pathogens early in life is beneficial to the education and development of the human immune system.

Over the past few decades, the healthcare community has observed an intriguing phenomenon: diseases related to the immune system – type 1 diabetes, and other autoimmune diseases, allergies, and the like – have taken hold in countries that have thriving, modern economies, while barely making a mark in the developing world. One of the best-supported theories to explain this peculiar public health pattern has been dubbed the hygiene hypothesis. The theory is based on the premise that exposure to pathogens early in life is actually beneficial to the education and development of the human immune system.

– Exposure to bacteria may play a pivotal role in the immune system, and that we might be able to understand what that role is by studying the human microbiome, says Aleksandar Kostic, a postdoctoral fellow in the lab of Ramnik Xavier at the Broad Institute of MIT and Harvard.

The work is the product of an extensive collaboration involving researchers at Aalto University, Broad Institute, University of Helsinki, the Novartis Institute of Biomedical Research, and other organizations across the globe working together as part of the DIABIMMUNE Study Group. By looking at the gut microbiomes of infants from three different countries, the team uncovered evidence that not only supports the hygiene hypothesis, but also points to interactions among bacterial species that may account, at least in part, for the spike in immune disorders seen in western societies.

Silent microbiomes

The DIABIMMUNE Study Group recruited and began collecting monthly stool samples from infants in each of the three countries: Finland, Estonia and Russian Karelia. Along with the samples, from which they would identify and quantify the bacteria that made up the infants’ gut microbiomes, they also collected lab tests and questionnaires about such topics as breastfeeding, diet, allergies, infections, and family history. They evaluated all of this data, which was collected from birth to age three from over 200 infants, to see whether connections might exist between disease incidence and what they found in the microbiome.

By characterizing the microbial content of the stool samples, the team found a sharp distinction between the microbiomes of Finnish and Estonian infants and their Russian Karelian counterparts: the gut microbiomes of the Finnish and Estonian infants were dominated by Bacteroides species, while Russian Karelian infants had an overrepresentation of Bifidobacterium early in life and an overall greater variability in their microbiomes over the course of the three years that samples were collected.

– We can only speculate why this difference in bacterial populations exists; what we could show was what implications that difference in populations might have, says Tommi Vatanen, a Doctoral candidate at the Aalto University and Broad who was a co-first author of the Cell study.

LPS has been well-known for its ability to trigger the immune system that LPS from the bacteria E. coli is commonly used to stimulate immune cells in laboratory experiments. But, it turns out, not all LPS are created equal.

When the researchers looked at LPS signaling in the Russian Karelian microbiome, they saw a familiar pattern: E. coli LPS led the charge, likely performing its usual role triggering the immune response. However, when the researchers looked at LPS signaling in the Finnish and Estonian microbiomes, they found that the LPS from the Bacteroides species ruled the roost. What’s more, they discovered that the particular form of LPS found in Bacteroides fails to activate the immune system and even stifles the immune-activating LPS from the E. coli and other bacteria living in those communities.

– We believe that E. coli, which lives in the infant gut in all three countries, might be one of the immune educating bacteria responsible for training the immune system early in life. But, we found that if you mix Bacteroides with E. coli it can actually inhibit the immune-activating properties of E. Coli, and we suspect this might have consequences on the development of the immune system, Vatanen explains.

– In the Finnish and Estonian infants, where Bacteroides dominates, the gut microbiome is immunologically very silent, Kostic adds, and continues – We believe that, later on, this makes them more prone to strong inflammatory stimuli.

The researchers suspect that the LPS immune activation by E. coli seen in the Russian Karelian infants is reflective of the relationship humans developed with microbiota over the course of human evolution. The prevalence and dominance of Bacteroides, in contrast, is a more recent phenomenon related in some way to improved sanitation and standard of living.

The researchers say that they would next like to investigate how and why Bacteroides has come to dominate in the infant gut in these westernized countries. They also plan to expand their studies to include other geographic regions and hope to uncover additional mechanisms that help explain the connection between the microbiome and immune-related disease.

Michael Knip of the University of Helsinki also served as a co-senior author of the study. Other researchers who contributed to the work include: Heli Siljander, Eric Franzosa, Moran Yassour, Raivo Kolde, Hera Vlamakis, Timothy Arthur, Anu-Maaria Hämäläinen, Aleksandr Peet, Vallo Tillmann, Raivo Uibo, Sergei Mokurov, Natalya Dorshakova, Jorma Ilonen, Suvi Virtanen, Susanne Szabo, Jeff Porter, Harri Lähdesmäki, Curtis Huttenhower, and Dirk Gevers.


Vatanen et al., Variation in Microbiome LPS Immunogenicity Contributes to Autoimmunity in Humans, Cell (2016),

Posted in Allergy, Asthma, Autism, Bacteria, bowel disease, co-morbid, diabetes, Environment, Epigenetics, Genetics, Gut, IBD, Immune System, Inflammation, Treatment | Leave a comment

Chronic Lack of Sleep – Linked to Neurological Damage – Implications for Autism ?

 Insomnia Linked to Damage in Brain Communication Networks

At A Glance

  • Twenty-three insomnia patients and 30 healthy controls were examined with diffusion tensor imaging and given questionnaires to evaluate mental status and sleep patterns.
  • Compared to the healthy controls, insomnia patients had altered white matter tract integrity in brain regions that regulate sleep, consciousness, and alertness.
  • White matter integrity abnormalities in insomnia patients may be caused by loss of myelin.

OAK BROOK, Ill. — Using a sophisticated MRI technique, researchers have found abnormalities in the brain’s white matter tracts in patients with insomnia. Results of the study were published online in the journal Radiology.

Primary insomnia, in which individuals have difficulty falling or staying asleep for a month or longer, is associated with daytime fatigue, mood disruption and cognitive impairment. Insomnia can also lead to depression and anxiety disorders

“Insomnia is a remarkably prevalent disorder,” said researcher Shumei Li, M.S., from the Department of Medical Imaging, Guangdong No. 2 Provincial People’s Hospital, Guangzhou, China. “However, its causes and consequences remain elusive.”

For the study, Li, along with colleagues lead by investigator Guihua Jiang, M.D., set out to analyze the white matter tracts in insomnia patients and the relationship between abnormal white matter integrity and the duration and features of insomnia.

“White matter tracts are bundles of axons—or long fibers of nerve cells—that connect one part of the brain to another,” Li said. “If white matter tracts are impaired, communication between brain regions is disrupted.”

The study included 23 patients with primary insomnia and 30 healthy control volunteers. To evaluate mental status and sleep patterns, all participants completed questionnaires including the Pittsburgh Sleep Quality Index, the Insomnia Severity Index, the Self-Rating Anxiety Scale and the Self-Rating Depression Scale.

Each participant also underwent brain MRI with a specialized technique called diffusion tensor imaging (DTI). DTI allows researchers to analyze the pattern of water movement along white matter tracts to identify a loss of tract integrity.

“We used a new method called Tract-Based Spatial Statistics that is highly sensitive to the microstructure of the white matter tract and provides multiple diffusion measures,” Li said.

Results of the analysis showed that compared to the healthy controls, the insomnia patients had significantly reduced white matter integrity in several right-brain regions, and the thalamus which regulates consciousness, sleep and alertness.

“These impaired white matter tracts are mainly involved in the regulation of sleep and wakefulness, cognitive function and sensorimotor function,” Li said.

In addition, abnormalities in the thalamus and body corpus callosum—the largest white matter structure in the brain—were associated with the duration of patients’ insomnia and score on self-rating depression scale.

“The involvement of the thalamus in the pathology of insomnia is particularly critical, since the thalamus houses important constituents of the body’s biological clock,” she added.

The study also found that underlying cause of white matter integrity abnormalities in insomnia patients may be loss of myelin, the protective coating around nerve fibers.

The researchers caution that further study needs to be done on a larger sample to clarify the relationship between altered white matter integrity and insomnia.


Further Readings of Interest


Posted in Autism, co-morbid, Environment, Neurology, Physiology, Treatment | Leave a comment

Environment x Genes – Fungicides and Autism

Could a new class of fungicides play a role in autism, neurodegenerative diseases?

A new UNC School of Medicine study shows how chemicals designed to protect crops can cause gene expression changes in mouse brain cells that look strikingly similar to changes in the brains of people with autism and Alzheimer’s disease.

March 31, 2016

CHAPEL HILL, NC – Scientists at the UNC School of Medicine have found a class of commonly used fungicides that produce gene expression changes similar to those in people with autism and neurodegenerative conditions, including Alzheimer’s disease and Huntington’s disease.

The study, published today in the journal Nature Communications, describes a new way to home in on chemicals that have the potential to affect brain functions.

Mark Zylka, PhD, senior author of the study and associate professor of cell biology and physiology at UNC, and his team exposed mouse neurons to approximately 300 different chemicals. Then the researchers sequenced RNA from these neurons to find out which genes were misregulated when compared to untreated neurons. This work created hundreds of data sets of gene expression; genes give rise to products, including proteins or RNA.

Zylka’s team then used computer programs to deduce which chemicals caused gene expression changes that were similar to each other.

“Based on RNA sequencing, we describe six groups of chemicals,” Zylka said. “We found that chemicals within each group altered expression in a common manner. One of these groups of chemicals altered the levels of many of the same genes that are altered in the brains of people with autism or Alzheimer’s disease.”

Chemicals in this group included the pesticides rotenone, pyridaben, and fenpyroximate, and a new class of fungicides that includes pyraclostrobin, trifloxystrobin, fenamidone, and famoxadone. Azoxystrobin, fluoxastrobin, and kresoxim-methyl are also in this fungicide class.

“We cannot say that these chemicals cause these conditions in people,” Zylka cautioned. “Many additional studies will be needed to determine if any of these chemicals represent real risks to the human brain.”

Zylka, a member of the UNC Neuroscience Center, and his group found that these chemicals reduced the expression of genes involved in synaptic transmission – the connections important for communication between neurons. If these genes are not expressed properly, then our brains cannot function normally. Also, these chemicals caused an elevated expression of genes associated with inflammation in the nervous system.  This so-called neuroinflammation is commonly seen in autism and neurodegenerative conditions.

The researchers also found that these chemicals stimulated the production of free radicals – particles that can damage the basic building blocks of cells and that have been implicated in a number of brain diseases. The chemicals also disrupted neuron microtubules.

“Disrupting microtubules affects the function of synapses in mature neurons and can impair the movement of cells as the brain develops,” Zylka said. “We know that deficits in neuron migration can lead to neurodevelopmental abnormalities. We have not yet evaluated whether these chemicals impair brain development in animal models or people.”

Jeannie T. Lee, MD, PhD, professor of genetics at Harvard Medical School and Massachusetts General Hospital, who was not involved in this research, said, “This is a very important study that should serve as a wake-up call to regulatory agencies and the general medical community. The work is timely and has wide-ranging implications not only for diseases like autism, Parkinson’s, and cancer, but also for the health of future generations. I suspect that a number of these chemicals will turn out to have effects on transgenerational inheritance.”

Zylka’s group also analyzed information from the U.S. Geological Survey, which monitors countywide pesticide usage, as well as the Food and Drug Administration and the U.S. Department of Agriculture, which test foodstuffs yearly for pesticide residues.

Of the chemicals Zylka’s team studied, only the usage of pyridaben has decreased since 2000. Rotenone use has remained the same since 2000. However, the use of all the fungicides in this group has increased dramatically over the past decade.

Indeed, a study from the Environmental Protection Agency found that pyraclostrobin is found on foods at levels that could potentially affect human biology, and another study linked pyraclostrobin usage to honeybee colony collapse disorder.

The pesticide rotenone was previously implicated in Parkinson’s disease through replicated animal experiments and through human epidemiological studies. A separate 2015 UNC study found that Parkinson’s disease is much more common in older adults with autism than in older adults without autism.

Previous work has also shown that a single dose of the fungicide trifloxystrobin reduced motor activity for several hours in female rats and for days in male rats. Disrupted motor function is a common symptom of Parkinson’s disease and other neurological disorders.  The related fungicide picoxystrobin impaired motor activity in rats at the lowest dose tested.

Zylka added, “The real tough question is: if you eat fruits, vegetables or cereals that contain these chemicals, do they get into your blood stream and at what concentration?  That information doesn’t exist.” Also, given their presence on a variety of foodstuffs, might long term exposure to these chemicals – even at low doses – have a cumulative effect on the brain?

Zylka noted that conventionally grown leafy green vegetables such as lettuce, spinach, and kale have the highest levels of these fungicides.  But due to each chemical’s effectiveness at reducing fungal blights and rust, crop yields have increased and farmers are expanding their use of these chemicals to include many additional types of food crops.

Zylka’s team hopes their research will encourage other scientists and regulatory agencies to take a closer look at these fungicides and follow up with epidemiological studies.

“Virtually nothing is known about how these chemicals impact the developing or adult brain,” Zylka said. “Yet these chemicals are being used at increasing levels on many of the foods we eat.”

This research was funded by three of the National Institutes of Health: the National Institute of Environmental Health Sciences, the National Institute on Neurological Disorders and Stroke, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Mark Zylka, PhD, is a member of the Carolina Institute for Developmental Disabilities and the UNC Lineberger Comprehensive Cancer Center. He was named director of the UNC Neuroscience Center in January and will take over for current director William Snider, MD, in July. Brandon Pearson, PhD, and Jeremy Simon, PhD, were co-first authors on the study. Additional authors from UNC include Eric McCoy, PhD, Giulia Fragola, PhD, and Gabriela Salazar.


Zylka’s previous work on drugs that affect autism-linked genes, published in Nature, can be found here.


Further Readings of Interest




Posted in Autism, co-morbid, Environment, Immune System, Inflammation, Neurology | Leave a comment

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

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


Posted in Autism, Environment, Genetics | Leave a comment