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Autistic Advocacy Group Condemns Presidential Appointment of Anti-Vaccine Activist Peter Bell

12 Jan

Peter Bell of Autism Speaks has been appointed to the President’s Committee for People with Intellectual Disabilities. As I read about the appointment I felt that there would be some reaction. Perhaps even a strong reaction. And, as you will see, I was correct. The Autistic Self Advocacy Network (ASAN) has issued a press release condemning the appointment.

Here is the press release:

FOR IMMEDIATE RELEASE

PRESS CONTACT:
Melody Latimer
Autistic Self Advocacy Network
Phone: 202-630-7477
mlatimer@autisticadvocacy.org

AUTISTIC ADVOCACY GROUP CONDEMNS PRESIDENTIAL APPOINTMENT OF ANTI-VACCINE ACTIVIST PETER BELL

Recent appointee Peter Bell has a long history of supporting fringe, anti-vaccine positions widely discredited in the scientific community

Washington, DC – January 12, 2012 – The Autistic Self Advocacy Network, the nation’s leading advocacy group run by and for Autistic adults, today expressed concern and disappointment over President Obama’s announcement Tuesday of his intent to appoint anti-vaccine activist Peter H. Bell as a member of the President’s Committee for People with Intellectual Disabilities.

“Bell’s appointment shows such contrast to the forward motion the Obama administration has shown in the areas of autism and disability as a whole,” said Melody Latimer, ASAN Director of Community Engagement and an autistic parent of autistic children herself.

Bell, Executive Vice President of Programs at Autism Speaks, has a long history of supporting anti-vaccination related causes, dating back to his time as President and CEO of Cure Autism Now, which merged with Autism Speaks in 2007. Despite wide ranging scientific evidence to the contrary, Bell and others in the anti-vaccine movement have long maintained the existence of a link, a position viewed as irresponsible by many public health advocates.

“The link between Autism and vaccines has long been discredited, and so an appointment placing an anti-vaccine leader in a position to influence a greater audience and re-open the issue is disappointing and ill-advised. We respect and appreciate the Obama Administration’s commitment to autism issues, but hope they will vet their appointees more carefully going forward,” Latimer noted.

Autism Speaks, Bell’s employer, has a checkered and controversial history. In 2009, Autism Speaks lashed out at the Department of Health and Human Services for refusing to incorporate research objectives connecting autism to vaccines in the Inter-Agency Autism Coordinating Committee’s Strategic Plan for Autism Research. In response to Autism Speaks’ disconnect from mainstream science on this question, several senior executives resigned from the organization in protest.

Autism Speaks has also been viewed with substantial controversy by Autistic people themselves, in large part due to the organization’s failure to meaningfully include individuals with the disability on their board of directors or in more than token roles in their senior leadership. Other criticisms of the organization include the low percentage of funds Autism Speaks invests in services, abnormally high executive salaries and what many have interpreted as deeply offensive advertising utilizing fear and pity to raise money. In 2009, the organization debuted its much-ridiculed video “I Am Autism” at the United Nations in New York City, presenting autism as an anthropomorphic force aiming to steal children. After widespread protests from Autistic adults across the country and criticisms from other disability organizations, Autism Speaks eventually pulled the promotional film.

The Autistic Self Advocacy Network (ASAN) is the nation’s leading advocacy organization run entirely by and for Autistic adults and youth. ASAN’s supporters include Autistic adults and youth, cross-disability advocates, family members, professionals, educators and friends. ASAN was created to provide support and services to individuals on the autism spectrum while working to change public perception and combat misinformation by educating communities about persons on the autism spectrum. The organization’s activities include public policy advocacy, community engagement to encourage inclusion and respect for neurodiversity, quality of life oriented research and the development of Autistic cultural activities and other opportunities for Autistic people to engage with others on the spectrum.

Brian Deer responds to David Lewis’ complaint

10 Jan

Much attention has been focused on Andrew Wakefield again recently. This follows Mr. Wakefield’s lawsuit against Brian Deer, Fiona Godlee and the British Medical Journal (BMJ). Also, a lengthy complaint authored by David Lewis was made public, detailing his views about the allegations of fraud levied against Mr. Wakefield by the BMJ.

The two are not directly related as Mr. Lewis’ complaint fails to address many of the issues raised by the BMJ in their articles alleging fraud. That said, If one pokes around Mr. Deer’s website, one will eventually stumble upon this page: David L Lewis: indignant abuse as complaints turn to nothing. There is an introduction to the subject including Mr. Deer’s interactions with Mr. Lewis followed by a point by point response to Mr. Lewis’ complaint. For anyone who may be thinking that Mr. Deer is intimidated by the complaint I encourage you to read the response. It is very much in the style of Brian Deer. For example

DAVID L LEWIS: “My report, which I have submitted to UCL, UKRIO and HEFCE, includes 72 emails exchanged between me and the BMJ’s editors.”

DEER: I offer the recipients at UCL, UKRIO and HEFCE my sympathy.

Aside from such dismissive statements, Mr. Deer takes on the many (often repetitive) claims by Mr. Lewis directly. Mr. Lewis’ complaint and main thesis in his rapid response to the BMJ focus on non-specific colitis as used in the Lancet paper: the histology grading sheets of Dr. Dillhon somehow prove that there was no fraud. It is a confusing argument because it doesn’t address the many issues raised by Mr. Deer and the BMJ.

Per Mr. Deer in his introduction:

These biopsy assessments, however, weren’t the basis upon which, in January 2011, the BMJ concluded that Wakefield’s MMR work was “an elaborate fraud”. The evidence we presented rested firmly on the GMC panel’s findings of research dishonesty, and was overwhelmingly related to Wakefield’s activities with regard to the admission of patients to the study, as well as the purported clinical histories and findings which lay behind a claim by Wakefield of a 14-day temporal link between the administration of MMR and the first “behavioural symptoms” of autism. We say this purported link was fraudulent.

Later, in response to Mr. Lewis’ claim:

DAVID L LEWIS: “… alleged that Andrew Wakefield fabricated the diagnosis of colitis in a 1998 Lancet study involving 12 children with autistic spectrum disorder (ASD).”

Mr. Deer responds:

DEER: At the core of our problems in dealing with Lewis is that nowhere was such an allegation made in the BMJ. He repeatedly identifies my feature “Autistic enterocolitis under the microscope”, published in April 2010, but this simply doesn’t make such an allegation. Plain reading would make this clear.

Not only can I find no foundation for this fundamental of Lewis’s complaint (and I think I’d remember forming any view at that time that the histopathology reporting in the Lancet was fraudulent, as distinct from, say, wrong, misleading or incompetent), we consulted legal counsel, before and after publication, and expert peer-reviewers. We remain unable to identify any text inferring Wakefield’s intent with regard to histology reporting. I’ve similarly asked Nature to identify any such text, and they too have failed

Mr. Lewis has taken issue with the fact that the BMJ did not print his rapid response exactly as submitted:

DAVID L LEWIS: “To support their new fraud theory, Godlee rewrote my Rapid Response, removing any evidence that undermined their allegations against Wakefield and others.”

DEER: Lewis’s rapid response was extensively re-written because it was false and defamatory. Legal advice was taken. Two peer reviewers rejected the submitted text. No changes had any effect in supporting any “fraud theory”, whether new or otherwise. Lewis approved the published text.

In hosting the words of Mr. Lewis, the BMJ would itself be responsible in part for any defamatory language included. This is the way of the law in the U.K..

In my opinion, the Mr. Lewis’ arguments are a side show of the the Wakefield saga (Yes, in my view Mr. Wakefield is a major side show in itself). They don’t address the substance of the claims of fraud put forth by the BMJ.

Navigating Love and Autism

9 Jan

If you haven’t already read it, Navigating Love and Autism, is worth your time. It is an article by Amy Harmon of the New York Times.

When I first saw the pictures from the article I though, “Hey, I know these guys!” It took me a minute to realize I know them from the series “Autism Talk TV” (the best TV on TV) with Alex Plank (if you don’t know Alex Plank, maybe you know his site: Wrong Planet)

I’ve been hoping to get the time to do a good piece on the article. In my delay, Seth Mnookin has done better than I could. Mr. Mnookin’s first piece is The New York Times’s incredible piece on the lives and loves of two adults with Aspergers” and the second is “SciWriteLabs 7.1: The New York Times’s Amy Harmon on neurodiversity and writing about autism is an interview with the author.

If you are a parent and your reaction is, “those aren’t the experiences of my kid”, I’d encourage you to check it out.

Besides, how can you stay away from a New York Times article with the following correction:

Correction: December 30, 2011

An article on Monday about Jack Robison and Kirsten Lindsmith, two college students with Asperger syndrome who are navigating the perils of an intimate relationship, misidentified the character from the animated children’s TV show “My Little Pony” that Ms. Lindsmith said she visualized to cheer herself up. It is Twilight Sparkle, the nerdy intellectual, not Fluttershy, the kind animal lover.

Around the blogosphere January 8 2012

8 Jan

Or, at least, a small fraction of it. There are times when I have to remind myself to get out and read more. Not papers, not news, but blogs. I don’t know why I have to remind myself. There is so much good stuff out there.

In no particular order, and for no other reason than these stuck in my mind for sometimes long periods of time, here are some blog posts and bloggers I’ve been reading:

When I first came into the online autism discussions one of my favorite writers was Jeanette (Mom26children). As you can gather, she has six children. Of those, 5 are autistic and she’s seen the breadth of the spectrum in them. The last post on her blog is from May, but it is a great one: Age (s) of Autism…. I Couldn’t Resist 🙂 . She tells us that two of her kids, kids who had major challenges as young children, no longer meet the criteria for special education. She credits her kids and the people who worked with them.

Emily Willingham is part of the Thinking Person’s Guide team. She has a Ph.D. in biology. That’s really only a starting point. She has the research background and, much more, repeated shows that she has science chops to delve into research papers on autism (as journal editor, this shouldn’t be surprising). In a recent post (On autism, sAPPa, immunity, and subsets ) she deconstructs the publicity around a recent paper. It’s a classic problem where the paper and the press release oversell the relevance to autism. This problem isn’t restricted to autism, by the way. I see it a lot where people try to link their work to some hot topic.

The Crowded Autism Web is a recent post from The Autistic Me. As the writer points out, The Autistic Me has been around for several years but 2012 is a year for expanding readership. Also, you can follow The Autistic Me on Twitter.

Shannon Rosa is another member of the Thinking Person’s Guide team. One thing TPGA does that I really wish I could do well is interviews. One example is Interview: Christa Dahlstrom of Flummox and Friends, where Ms. Rosa interviews the creator of a live-action show which looks to explore social interactions. “[A] little bit Pee Wee’s Playhouse, mixed with The Big Bang Theory, with a little old-school Electric Company thrown in.

http://www.kickstarter.com/projects/2055453201/flummox-and-friends/widget/video.html

The Autism Vaccine Controversy and the Need for Responsible Science Journalism

7 Jan

The Huffington Post has a new section on science. One of the first articles discusses the “Autism Vaccine Controversy”. In The Autism Vaccine Controversy and the Need for Responsible Science Journalism, Seth Mnookin starts out:

Earlier this week, The Panic Virus, my book on the controversy over vaccines and autism, was released in paperback. While there haven’t been many scientific advances in this particular issue since the hardcover edition was published — the evidence supporting vaccines’ paramount place in public health efforts and the total lack of corroboration supporting a causal connection between vaccines and autism remain as strong today as they were a year ago — there have been new developments in the story. Their coverage highlights an enduring passion of mine: The need for reliable, responsible science journalism.

Yes, Seth Mnookin, author of The Panic Virus, is writing for the Huffington Post, a site which has contributed greatly to misinformation about vaccines and autism. The Huffington Post has been home to David Kirby (who was a major promoter of the mercury/autism concept) as well as welcoming input from Jenny McCarthy and Jim Carrey, to name but a few of the poor choices for writers the Post engaged.

On PLoS blogs, Mr. Mnookin announced this new gig with Has the Huffington Post embraced science & closed the door on anti-vaccine quackery? We can hope. I wouldn’t place any bets on it though.

No Evidence of Murine Leukemia Virus-Related Viruses in Live Attenuated Human Vaccines

6 Jan

There has been much discussion of XMRV, Xenotropic murine leukemia virus-related virus, here at Left Brain/Right Brain and elsewhere in the past few months. The reason for the discussion here is the (now shown to be false) idea that XMRV is implicated in autism causation. Two papers have addressed this question and found no evidence of a link. XMRV came to prominence as a possible candidate in causing chronic fatigue syndrome (CFS). Multiple papers have found no evidence of a link between XMRV and CFS (fan example is discussed here) and the original paper on the topic was withdrawn by editors of the journal Science after it became clear that those results were suspect.

The idea that autism and XMRV was promoted by David Kirby, whose efforts also strongly promoted the debunked autism-epidemic-caused-by-mercury idea. Mr. Kirby’s article at the Huffington Post was Is Autism Associated with A Viral Infection?. In this he quoted CFS/XMRV researcher Judy Mikovits:

And then Dr. Mikovits dropped a bombshell that is sure to spark controversy.

“On that note, if I might speculate a little bit,” she said, “This might even explain why vaccines would lead to autism in some children, because these viruses live and divide and grow in lymphocytes — the immune response cells, the B and the T cells. So when you give a vaccine, you send your B and T cells in your immune system into overdrive. That’s its job. Well, if you are harboring one virus, and you replicate it a whole bunch, you’ve now broken the balance between the immune response and the virus. So you have had the underlying virus, and then amplified it with that vaccine, and then set off the disease, such that your immune system could no longer control other infections, and created an immune deficiency.”

Mr. Kirby went on to write:

So there you have it – a possible explanation of regressive autism in a significant number of cases associated with immune system deregulation triggered by vaccination.

Of course, much more work is needed to nail down the exact significance of such an association. For example, is the virus implicated in the cause of autism, or do children harbor the virus as a result of autism?

Yes, Ms. Mikovits and David Kirby were proposing a possible link between autism, XMRV and (of course) vaccines.

That was October 2009. Fast forward to today, two years later and we see

A) Neither Ms. Mikovits nor anyone else has published the data supposedly linking XMRV and autism

B) Two studies have looked for evidence (and failed to find any) of a link between XMRV and autism,

Lack of infection with XMRV or other MLV-related viruses in blood, post-mortem brains and paternal gametes of autistic individuals.

PCR and serology find no association between xenotropic murine leukemia virus-related virus (XMRV) and autism.

C) Evidence has arisen that much of the data linking XMRV to CFS is faulty.

Studies on XMRV are still ongoing. If experience from the vaccine-autism-epidemic idea tell us anything, the idea that XMRV causes CFS and/or autism will die slowly and even more data are needed.

To that end, a recent study explored whether XMRV is a contaminant in live virus vaccines. (note that in other vaccines, the XMRV is likely as dead as the other constituents of the vaccine). You can tell the result from the title: No Evidence of Murine Leukemia Virus-Related Viruses in Live Attenuated Human Vaccines.

Background

The association of xenotropic murine leukemia virus (MLV)-related virus (XMRV) in prostate cancer and chronic fatigue syndrome reported in previous studies remains controversial as these results have been questioned by recent data. Nonetheless, concerns have been raised regarding contamination of human vaccines as a possible source of introduction of XMRV and MLV into human populations. To address this possibility, we tested eight live attenuated human vaccines using generic PCR for XMRV and MLV sequences. Viral metagenomics using deep sequencing was also done to identify the possibility of other adventitious agents.

Results

All eight live attenuated vaccines, including Japanese encephalitis virus (JEV) (SA-14-14-2), varicella (Varivax), measles, mumps, and rubella (MMR-II), measles (Attenuvax), rubella (Meruvax-II), rotavirus (Rotateq and Rotarix), and yellow fever virus were negative for XMRV and highly related MLV sequences. However, residual hamster DNA, but not RNA, containing novel endogenous gammaretrovirus sequences was detected in the JEV vaccine using PCR. Metagenomics analysis did not detect any adventitious viral sequences of public health concern. Intracisternal A particle sequences closest to those present in Syrian hamsters and not mice were also detected in the JEV SA-14-14-2 vaccine. Combined, these results are consistent with the production of the JEV vaccine in Syrian hamster cells.

Conclusions

We found no evidence of XMRV and MLV in eight live attenuated human vaccines further supporting the safety of these vaccines. Our findings suggest that vaccines are an unlikely source of XMRV and MLV exposure in humans and are consistent with the mounting evidence on the absence of these viruses in humans.

Yes, there is no evidence of XMRV in vaccines. This is rather anticlimactic given the evidence already in place that XMRV is not linked to autism, and the fact that the XMRV/CFS link is already tenuous at best.

The blogger erv has done the most thorough job following the XMRV study out there, including discussing the paper above. Others have taken up where David Kirby left off and promoted the idea that XMRV and autism are linked, and that vaccines are a possible part of that link. I would hope that those people would see the value in letting their readers know about this paper (and others, and the retractions).

BMJ instructs lawyers to “defend the claim vigorously” against Andrew Wakefield’s lawsuit

6 Jan

The British Medical Journal (BMJ) has issued a press release (below) about the lawsuit initiated by Andrew Wakefield claiming defamation arising from a series of articles published last year. The BMJ and Mr. Deer stand by their articles and statements and have instructed their attorneys to “defend the claim vigorously”.

Although not formally served with the legal papers, the BMJ is on notice that Andrew Wakefield has issued defamation proceedings, not in London as might be ordinarily expected as concerns a predominately English publication, but in Texas, USA, where he now lives. The proceedings primarily relate to an article written by Brian Deer and published a year ago on 5 January 2011, entitled Secrets of the MMR Scare: How the Case Against the MMR Vaccine was Fixed, and an accompanying editorial which related to Mr Wakefield’s now infamous Lancet Paper on MMR.

Of course, following the findings of the British General Medical Council’s Fitness to Practice Panel and Mr Wakefield’s history of pursuing unfounded litigation, any action brought against the BMJ and Mr Deer in London would have been immediately vulnerable to being struck out as an abuse of process.

Despite the findings of the GMC’s Fitness to Practice Panel and his co-authors having publicly retracted the causation interpretation put forward by the Lancet Paper, it would appear from the Claim filed at court that Mr Wakefield still stands by the accuracy of the Lancet paper and his conclusion therein, thereby compounding his previously found misconduct. While we await formal service, unsurprisingly the BMJ and Mr Deer standby the material published in the BMJ and their other statements and confirm that they have instructed lawyers to defend the claim vigorously.

NOTES TO EDITORS

1. The Lancet Paper was published on 23 February 1998 entitled “Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children”. Its claims of a temporal association between MMR vaccine and autism were retracted by the authors (excluding Mr Wakefield) on 6 March 2004, following the first findings from Brian Deer’s investigation for The Sunday Times. The paper was retracted in its entirety by the Lancet on 2 February 2010, with the Lancet noting that elements of the paper “have been proven to be false” during hearings of a General Medical Council fitness to practise panel.

2. Following a 217-day investigation by the GMC’s panel, on 24 May 2010, the panel found Mr Wakefield guilty of serious professional misconduct. It found that Mr Wakefield “had a clear and compelling duty to ensure that the factual information contained in the [Lancet] paper was true and accurate and he failed in this duty”. The Panel also found that Mr Wakefield was intentionally dishonest and misleading in describing the patient population, and that he had been dishonest when questioned about it later. Similarly, the panel stated that “the description of the referral process was irresponsible, misleading, and in breach of [Mr] Wakefield s duty as a senior author”. The Determination also set out how Mr Wakefield compounded his misconduct by failing to correct the content of the paper.

3. As a result of Mr Wakefield’s “persistent lack of insight” into his behaviour, the GMC determined that his name should be erased from the medical register.

4. Mr Wakefield adduced no evidence in mitigation and made no arguments or pleas in mitigation in front of the Fitness to Practice panel. He did not appeal its decision and has not attempted to replicate the Lancet paper’s findings in order to attempt to vindicate his position.

5. At various times in the past, Mr Wakefield has brought claims and made complaints against Mr Deer, The Sunday Times, Channel Four and Twenty Twenty Productions in respect of allegations of dishonesty relating to his Lancet paper. In no case has he been successful. Indeed, in each instance the case has been dropped by Mr Wakefield. In Wakefield v Channel Four Television Corporation, Twenty Twenty Productions Ltd and Brian Deer [2005] EWHC 2410 (QB) Mr Justice Eady refused to grant a stay sought by Mr Wakefield, stating that the case would turn on fundamentally serious issues going to the heart of the Claimant s honesty and professional integrity.

In refusing the stay, Eady J considered Mr Wakefield’s conduct in relation to the various proceedings he had brought. He noted that Mr Wakefield had written to a number of other organisations including: the Cambridge Evening News; Evan Harris (an MP who criticised Mr Wakefield on a radio programme); and the Department of Health (which provided a link on its website to the Channel Four Dispatches website).

Mr Wakefield informed these entities in correspondence that he had issued proceedings against The Sunday Times, Mr Deer and/ or Channel Four, indicating that proceedings were ongoing. He made no mention of the stays which he had obtained, or was seeking. Eady J considered this misleading, and concluded that Mr Wakefield wished to use the existence of the libel proceedings for public relations purposes, and to deter critics, while at the same time isolating himself from the downside of such litigation, in having to answer a substantial defence of justification. The Judge believed that there was a pattern of using the existence of libel proceedings, albeit stayed, as a tool for stifling further criticism or debate.

6. On 2O December 2011, the BMJ’s solicitors, Farrer & Co, wrote to Mr Wakefield’s Texan lawyers setting out the matters referred to above, as well as other points. No response has been received.

7. Mr Wakefield’s allegations, that the MMR vaccines causes or contributes to autism, were investigated in three test cases in the United States Court of Federal Claims, heard from July 2007 and with judgments handed down on 12 February 2009. Although listed as a witness, Mr Wakefield was not called to give evidence, and his allegations were rejected. The judgments were upheld on appeal. In the lead case, Cedillo v Secretary for Health and Human Services, Special Master George Hastings said in his judgment with regard to evidence in the case: “Therefore, it is a noteworthy point that not only has that autistic enterocolitis theory not been accepted into gastroenterology textbooks, but that theory, and [Mr] Wakefield s role in its development, have been strongly criticized as constituting defective or fraudulent science.”

Simons Foundation: Notable papers of 2011

5 Jan

The Simons Foundation has an article discussing their choices of Notable papers of 2011. Below are their choices and links to the Simons Foundation blog (SFARI) articles which discuss them. Also given are links to pubmed for the original research articles.

Study finds high rate of autism in South Korea
Pubmed

Family sequencing study boosts two-hit model of autism
Pubmed

Networks of genes altered in autism brains, study says
Pubmed

Studies find high rate of rare new mutations in autism
Pubmed
Pubmed
Pubmed

Protein networks link different forms of autism, study says
Pubmed

Experts critique statistics, conclusion of autism twin study
Pubmed

Large study finds ‘baby sibs’ at high risk of autism
Pubmed

Autism tests struggle to balance accuracy and speed
Pubmed

Tuberous sclerosis, fragile X may be molecular opposites
Pubmed

Neurons made from stem cells reveal cellular flaws in autism
Pubmed

Autism Speaks: Top Ten Autism Research Achievements of 2011

5 Jan

Autism Speaks has a list of Top Ten Autism Research Achievements of 2011. Here is their list (which they state is not in an order of importance) with links to their articles discussing them:

It’s More than Just Genes…
Population Screening Reveals Dramatically Higher Autism Rates…
Baby Siblings at Risk…
De Novo Genetic Changes Provide New Clues for Autism…
Different Forms of Autism Share Striking Brain Similarities…
Prenatal Vitamins Before and After Conception May Decrease Autism Risk…
Gene Knockout Mouse May Offer Leap Forward in Autism Animal Models…
Tweaking Electrical Activity in the Brain Impairs & Restores Mouse Social Behaviors…
More Evidence Linking Immune System to Some Forms of Autism…
Earlier Autism Screening Shows Promise…

NIMH’s Top 10 Research Advances of 2011

5 Jan

Below is a blog post, NIMH’s Top 10 Research Advances of 2011, from the blog of Tom Insel, director of the National Institute of Mental Health (NIMH) in the U.S..

Tom Insel is the chair of the Interagency Autism Coordinating Committee (IACC), which creates the Strategic Plan for autism research funded by the U.S. government.

It is very interesting to see how often autism research is noted in the list below.

Item 3: Ricardo Dolmetsch’s work using stem cells to study autism and Timothy syndrome. (discussed here on Left Brain/Right Brain)

Item 4: De Novo Genetic Variants and autism

Item 8: NDAR, the National Database for Autism Research

and

Item 10: Public Private Partnerships.

At NIMH and in our broad research community, this has been a year of exciting discoveries and scientific progress, as we strive to make a difference for those with mental illness. Here are 10 breakthroughs and events of 2011 that are changing the landscape of mental health research.
1. Complexity: Discovering New Sources of Genetic Variance.

The discovery of two new sources of genetic variation may have an enormous impact on mental health research.

Students in “Genetics 101” learn that messenger RNA precisely mirrors the DNA sequence from which it was transcribed. However, recent studies suggest a far more complex transmission of information. NIMH-funded researchers compared corresponding RNA and DNA sequences in 27 individuals, and found more than 10,000 sequence sites where the RNA and DNA of the same individual did not match (1). These RNA-DNA mismatches were found in multiple study participants and in different types of cells, including brain and skin cells.
Another study presents what may be the most extraordinary discovery of 2011: somatic ‘retrotransposition’ can alter brain tissue (2). Retrotransposons are mobile genetic elements that can copy and insert themselves within a genome causing mutations in dividing cells. Although these insertions rarely lead to harmful effects when they occur in germ line cells (sperm and egg), they are frequently harmful if they occur in somatic cells, such as neurons. While nearly all studies of the genetics of mental illness have focused on germ line DNA, this new discovery suggests that DNA variation occurring in the developing brain could contribute to mental illness, just as mutations in mature tissues contribute to cancer. These surprising findings suggest a whole new frontier for the biology of mental illness.

2. Transcriptome: Developing Brains Have Unique Molecular Signatures.

Messenger RNAs, or transcripts, are intermediate products that carry the message from DNA, the genetic blueprint, to create proteins, and ultimately, the many different cell types throughout the brain. Each gene can make several transcripts, which are expressed in patterns unique to each of us. To better understand how these patterns of gene expression influence the developing brain, NIMH supported the first map of how RNA expression changes across the life span through two parallel studies of postmortem brains, ranging in age from two weeks after conception to 80 years old (3, 4). The researchers found that nearly 90% of genes are expressed differently during prenatal development, infancy, and childhood. While each of these stages has a distinct transcriptional identity, the fetal brain looks like a different organ compared to the postnatal brain, with 60% of genes expressed differently and 83% of transcripts processed to make unique proteins. Many of the genetic variations associated with mental illness appear to have a specific effect on the form of the gene expressed uniquely during fetal life.
3. Induced Pluripotent Stem Cells: Disease in a Dish.

In 2011, induced pluripotent stem cells (iPSCs) enabled a new round of findings on anomalies in neurodevelopment underlying disorders of mental health. The technology permits scientists to take adult cells and reprogram them to have the capabilities of stem cells to divide and differentiate into specific cell types. Growing iPSCs from adults with diagnosed disorders permits direct observation in cell culture of how the development of neurons is altered in these disorders from the very earliest stages. Scientists studying cells from patients with Timothy syndrome, a condition in which children often show autism-like symptoms, and Fragile X syndrome, an inherited cause of intellectual disability, found the kinds of changes in developing neurons that would disrupt their ability to form normal neural networks and tissues (5, 6). Strikingly, observations of iPSCs derived from patients with schizophrenia showed changes in neurons at stages that would correspond to very early development, years before symptoms emerge (7, 8). These reprogrammed cells also offer a means of medications testing; in these studies, scientists were able to observe the effects of medications in cells from patients with Timothy syndrome and schizophrenia.
4. De Novo Genetic Variants.

This year scientists looking at families with only one case of autism found that up to eight percent of cases in these families were the result of de novo (unique to the person affected) copy-number variants—stretches of DNA that were either multiplied or truncated (9, 10). Analysis of the gene regions affected by these variants implicated a network of genes involved in the development of synapses and neuronal function (11). Another study, focusing specifically on sequences of DNA that code for protein, yielded other de novo genetic changes in one-case families (12). While providing information on genetic contributors to a significant fraction of sporadic autism cases, the work also reveals gene regions for future investigation and ultimately, information on functional changes underlying autism that will offer clues to therapy.
5. Epigenomics: How Experience Alters Behavior.

In any one individual, patterns of gene expression vary widely among cells, leading to a diversity of cell types and functions, even though the cells all have the same DNA sequence. Epigenetic processes—heritable changes in gene expression that are not related to DNA sequence—help explain this diversity. Research suggests that epigenetics may also be a sort of programming language through which experience can have lasting effects on behavior, not only in an individual over a lifetime, but across generations. This effect was demonstrated in a 2011 study of male mice exposed to social defeat—repeated bullying by another aggressive male (13). The bullied males developed behavior resembling depression, and in subtle ways, so did their offspring. This was true even though contact between mother and bullied father was brief and took place well before the birth of the young, suggesting that epigenetic mechanisms played a role. Understanding the nature of epigenetic changes opens possibilities for therapy; scientists also showed this year that they could reverse the silencing of a gene involved in a rare neurodevelopmental disorder, a proof of concept for interventions targeting epigenetic processes (14).
6. Grand Challenges in Global Mental Health.

Mental, neurological, and substance use (MNS) disorders account for 13% of the global burden of disease, more than cancer and cardiovascular disease (15). The Grand Challenges in Global Mental Health initiative, led and funded by NIMH, assembled the largest ever international Delphi panel—over 400 participants representing work conducted in 60 countries—to determine priorities for research relevant to MNS disorders (16). The initiative convened an international community of research funders, engaged them in the consensus-building process, and has already resulted in a $20 million (Canadian) commitment to fund research targeting one Challenge. To date, the Grand Challenges have served as a resource for organizations and governments as they select policy and mental health services priorities. Moreover, the Grand Challenges come at a time of increasing recognition of the economic costs of mental illness (17) and the importance of including mental health in global health care (18, 19).
7. Precision Medicine.

In most fields of medicine, focusing on clinical symptoms is no longer adequate for diagnosis. In line with the National Academy of Sciences’ call for the development of a new nosology based on multiple levels of analysis across medicine, NIMH continues to advance the Research Domain Criteria (RDoC) project. Aiming to define basic dimensions of functioning, from genes to neural circuits to behaviors, RDoC will cut across traditional disorder definitions and facilitate rapid progress in basic neurobiological and behavioral research. In psychiatry, as in other fields of medicine, such an integrated understanding of the foundations of mental disorders may lead the development of new or more personalized treatments.
8. NDAR.

For those familiar with the National Database for Autism Research (NDAR) and its mission to accelerate discovery in autism research, the naming of this resource as one of the top three HHS Secretary’s picks in the HHSinnovates program this fall was well-deserved recognition. As the largest database of its kind to date, NDAR provides approved users with simultaneous access to an unprecedented amount of autism research data, tools, and related resources, drawing on records directly submitted to NDAR as well as from four partner databases—the Autism Speaks’ Autism Genetic Resource Exchange (AGRE) and Autism Tissue Program, the Kennedy Krieger Institute’s Interactive Autism Network (IAN), and the NIH Pediatric MRI Data Repository. Approved NDAR users will have access to data from the 25,000 research participants represented in NDAR, as well as 2,500 AGRE families and more than 7,500 participants who reported their own information to IAN. In the two years since its launch, NDAR has managed to set a new standard for data sharing and collaborative research, not only for autism, but other fields as well.
9. New Culture of Discovery: Team Science.

In an age when events in one country can inspire and incite action in another, so too has global research become a more interconnected and collaborative community. Last year, we saw this with the 1000 Connectomes project, which collected resting state fMRI maps of the brain from over 1000 people around the world and made these results broadly accessible via the Neuroimaging Informatics Tools and Resources Clearinghouse (NITRC). This year, we saw this cultural shift toward team science when the Psychiatric Genomic Consortium reported on genetic variants associated with bipolar disorder and schizophrenia based on over 100,000 samples collected from 200 scientists in 65 institutions and 19 countries. Moreover, 2011 was the year when “standardization, integration, and data sharing” became a mantra for all science at NIMH, ensuring that results from individual labs could be leveraged by the global scientific community.
10. Public Private Partnerships.

As the pharmaceutical industry withdrew from psychiatric medication research and development this year, several new public-private efforts began to re-define the pathway for discovering new treatments. Arch2POCM, a public-private partnership comprising academic, industry, and regulatory scientists and clinicians, created a “precompetitive” initiative, free of intellectual property, for identifying new medications for schizophrenia and autism (20). One Mind for Research grew out of Patrick Kennedy’s moonshot for the mind, building an umbrella organization for neuroscience research related to all brain diseases. The Critical Path Institute led the way with common data elements for clinical research and new tools to promote data sharing. In addition, the Biomarkers Consortium brought industry, advocates, FDA, and NIH together to define biomarkers for neuropsychiatric diseases.
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