Large-scale analysis shows brain inflammation is a hallmark of autism - Parallels with ME/CFS?

A large-scale autopsy study performed by Johns Hopkins has revealed that the brains of people with autism show chronic inflammation produced by microglial activation. This study echoes recent findings by Nakatomi et al. showing microglial activation in the brains of people with ME/CFS.

Microglia are the first line of immune defense in the central nervous system, which means microglial activation is an indicator of inflammation. Chronic activation of microglia can lead to excitotoxicity, a mechanism that has been previously proposed for both Gulf War Illness and Autism (Blaylock, "Chronic Microglial Activation and Excitotoxicity Secondary to Excessive Immune Stimulation: Possible Factors in Gulf War Illness and Autism”). The John Hopkins study acts as confirmation that excitotoxicity caused by chronic inflammation is central to autism.

Excitotoxicity has been put forth as a mechanism of ME/CFS by a number of clinicians and researchers, including Drs. Paul Cheney, Jay Goldstein, Morris and Maes, Martin Pall, and, most recently, Jarred Younger.

What are the implications of this study for ME/CFS? As many have stated, it is clear that there is a connection between neuro-inflammation and a number of illnesses that show CNS and immune abnormalities. This study provides anatomical proof of inflammation in the brains of one of the illnesses on the neuro-immune spectrum, which opens the door for badly needed autopsy studies on ME/CFS patients, particularly those with severe illness. 

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Brain inflammation a hallmark of autism, large-scale analysis shows

By Shawna Williams

Press Release: Johns Hopkins, December 10, 2014. While many different combinations of genetic traits can cause autism, brains affected by autism share a pattern of ramped-up immune responses and related inflammation, an analysis of data from autopsied human brains reveals.

The study, a collaborative effort between Johns Hopkins and the University of Alabama at Birmingham, included data from 72 autism and control brains. It was published online last week in the journal Nature Communications.

"There are many different ways of getting autism, but we found that they all have the same downstream effect," says Dan Arking, an associate professor in the McKusick-Nathans Institute for Genetic Medicine at the Johns Hopkins University School of Medicine. "What we don't know is whether this immune response is making things better in the short term and worse in the long term."

The causes of autism, also known as autistic spectrum disorder, remain largely unknown and are a frequent research topic for geneticists and neuroscientists. But Arking had noticed that for autism, studies of whether and how much genes were being used—known as gene expression—had thus far involved too little data to draw many useful conclusions. That's because unlike a genetic test, which can be done using nearly any cells in the body, gene expression testing has to be performed on the specific tissue of interest—in this case, brains that could only be obtained through autopsies.

To combat this problem, Arking and his colleagues analyzed gene expression in samples from two different tissue banks, comparing gene expression in people with autism to that in controls without the condition. All told, they analyzed data from 104 brain samples from 72 individuals, the largest data set so far for a study of gene expression in autism.

Previous studies had identified autism-associated abnormalities in cells that support neurons in the brain and spinal cord. In this study, Arking says, the research team was able to narrow in on a specific type of support cell known as a microglial cell, which polices the brain for pathogens and other threats. In the autism brains, the microglia appeared to be perpetually activated, with their genes for inflammation responses turned on.

"This type of inflammation is not well understood, but it highlights the lack of current understanding about how innate immunity controls neural circuits," says Andrew West, an associate professor of neurology at the University of Alabama at Birmingham who was involved in the study.

Arking notes that, given the known genetic contributors to autism, inflammation is unlikely to be its root cause. Rather, he says, "This is a downstream consequence of upstream gene mutation."

The next step, he says, would be to find out whether treating the inflammation could ameliorate symptoms of autism.

Other authors on the study are Simone Gupta, Shannon E. Ellis, Foram N. Ashar, Anna Moes, Joel S. Bader, and Jianan Zhan, all of The Johns Hopkins University. The study was funded by the Simons Foundation and the National Institute of Mental Health.

Journal Reference: Simone Gupta, Shannon E. Ellis, Foram N. Ashar, Anna Moes, Joel S. Bader, Jianan Zhan, Andrew B. West, Dan E. Arking. Transcriptome analysis reveals dysregulation of innate immune response genes and neuronal activity-dependent genes in autism. Nature Communications, 2014; 5: 5748 DOI: 10.1038/ncomms6748

US Disabled Hold Protests at Bethesda

Photo credits Christine Jarrett

By Russell Logan

From Press Release: December 10, 2014. Protesters rallied outside the NIH campus in Bethesda MD on December 10, angry at the US government’s continued neglect and mistreatment of one million disabled Americans with ME (myalgic encephalomyelitis).

National Institutes of Health (NIH) officials were bunkered down in a special P2P meeting to plan the government’s ongoing response to patient concerns.

The protesters demanded the government adopt the Canadian Consensus Criteria (CCC) for ME, already well accepted and supported by researchers and clinicians, and the cancellation of the IOM (Institute of Medicine) contract to redefine ME.

Protest organizer Tom Jarrett, of Westfield, IN, was among those calling for a halt to the ME redefinition report being produced by NIH and the Department of Health and Human Services (HHS), which they think will set back their cause by decades.

Jarrett says that although he has lost his livelihood as a former estate and certified financial planner to ME, he has not lost his fighting spirit.

“NIH is not truly listening to what the patients say. Internal NIH emails obtained through a FOIA lawsuit stating ‘File all these responses. No need to answer them directly’ prove this claim,” he said.

“They have a pre-set agenda for this P2P workshop and the corresponding IOM redefinition effort, and they intend to carry it out regardless of what patients and their doctors say. We are here to protest these redefinition projects that waste taxpayer money and harm patients by moving research backward in time, away from neuro-immune biomarkers, and toward the generic symptom of fatigue.”

ME patients have formed a new advocacy body in response to NIH neglect. ME Advocacy already has established a fighting fund and has engaged a prominent public relations firm to further their cause.

“There is so much at stake here for my family and for the ME community,” Jarrett said. “Will the P2P meeting and resulting report result in decades more of neglect, while my sons grow up without a healthy father, and patients with ME suffer and die, saddled with a vague disease definition, a trivializing name, and no hope of a cure? I don’t think so, because we patients will keep fighting until the NIH stops and truly listens to our voices.”

For nearly 30 years, people with the debilitating disease, ME, often referred to in the US by the disparaging name of “chronic fatigue syndrome”, have suffered the ravages of a neuro-immune disease that has left many confined to their beds or homes in pain and dysfunction.

Since the reported outbreak of the disease in Incline Village, Nevada in the mid 1980s, the federal government has done little to support research into ME.

A scant 5 million dollars per year has been allocated for research into ME, a disease that affects more than one million Americans and which costs the country more than $17 billion annually in lost productivity and medical costs.


So little has been spent on educating physicians about the disease that fewer than 15% of doctors can explain what it is.

About the Author: Russell Logan has worked in advertising and magazine publishing for 30 years. He was a government speech writer, managing editor of the Brisbane Weekly magazine and ran his own magazine publishing company until forced into early retirement through ill health with ME. He has battled with moderate to severe ME for 25 years. He now lives in Noosaville, Australia, where he edits Shoutout About ME, an online magazine with breaking news about ME events, advocacy, and research.

Help the National ME/FM Action Network win $5000!

Thank you to everyone who voted!! The National ME/FM Action Network made it to the finals! It will now receive $5,000 and is eligible for a possible grand prize of $100,000 in January.  

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You can vote once a day, every day, until the semi-finals are over on December 10. 

Voting is easy. Just sign in automatically with your Facebook account and click on Vote. (You can also sign in with your email.) 

The National ME/FM Network is currently in 19th place, up from 20th place yesterday. To boost them into the top rank vote HERE.

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From the website:

Advancing Research in Canada for Myalgic Encephalomyelitis and Fibromyalgia

The NATIONAL ME/FM ACTION NETWORK is a Canadian charitable organization dedicated to Myalgic Encephalomyelitis (ME), also known as Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia (FM) through support, advocacy, education and research.

The 2010 Canadian Community Health Survey (CCHS) conducted by Statistics Canada revealed that there were 411,500 Canadians diagnoses with ME/CFS and 439,000 with Fibromyalgia. The survey also revealed a high level of disability for patients with ME/CFS and FM as well as unmet health care needs. ME/CFS and FM are chronic and severely disabling illnesses. They are as disabling as MS and are more prevalent in Canada than breast cancer, MS and AIDS combined! People are frequently bedridden and become isolated from friends and family – invisible in their own communities. These illnesses are real; the people are real; and they need help NOW!

These illnesses do not discriminate. All races, men and women, rich and poor, adults and children can be afflicted. It is devastating when a child is forced to cope with such a disabling illness.

Currently there are no definitive biomarkers or treatment protocols for ME or FM. Diagnosis is made by comparing patient symptoms with diagnostic criteria, then excluding other possible causes of those symptoms. Treatments are merely a means to manage the symptoms. There is no known prevention or cure. Lacking these basic fundamentals has an enormous impact on our current community and the thousands of people still struggling to be diagnosed. It typically takes years to obtain a proper diagnosis and it’s known that early intervention increases the chance of recovery. We need more research now!

To date, minimal funds have been available resulting in little biomedical research in Canada for these illnesses. Our Canadian patient community are asking for and are in need of biomedical research and solutions. Internationally, patient groups are beginning to take a leadership role by organizing and fundraising to advance research. It’s time Canada takes a lead role in advancing research and shines a light on the severity and complexities of these illnesses.

With the proceeds from the Aviva contest, the National ME/FM Action Network will establish a research arm that will take on the challenge of advancing biomedical ME and FM research in Canada. This will require some legal and accounting expenses. We will unite Canada’s experts and assemble an advisory group, establish our research criteria, investigate the various research opportunities requiring funding, choose our first project and support the execution and reporting of its results in 2015. The research project will incur expenses for salaries for research personnel (postdoc and graduate students) to conduct the study and prepare a paper for publication, expenses for sample selection and participant coordination, cost of laboratory materials used, and charges for use of a facility’s equipment for analysis of the samples. Also a webinar is planned to share the results. We have several exciting research opportunities to choose from to pursue and complete in 2015 that will benefit not only Canadians but millions of people worldwide, today and in the years to come. To support our researchers, we will use a portion of the funds to complete an international investigation of options to make a biobank available for future Canadian research projects. We also use funds to engage our patient community to determine their preferences for future projects and to communicate our plans with them and the media. Additionally, we will work to build on our relationship with government to obtain long term funding for other projects and to increase their awareness of the 850,500 Canadians in need of their support. This will involve the expense of meetings, mailings and possibility the hiring of a grant writer. The Aviva funds will permit us to solidify the direction of research in Canada and make a significant contribution towards improving the lives of current and future ME and FM patients.

Aviva’s gift will help to us make a difference to the lives of many Canadians.

It will give us credibility in our quest for answers and solutions and hope for a better tomorrow.

VOTE HERE.