Archive | Orgs RSS feed for this section

Recent Autism Gastrointestinal research funded by NIH

24 Jul

There are many parent advocates asking for research into gastrointestinal disorders and autism. My own anecdotal observations have been that these same parent advocates are of the belief that no work is ongoing. There are a number of projects ongoing and I’ve tried in the past to make that point (What projects are being funded in autism research? Part 1: vaccines and GI issues). I found 14 projects, nearly $3M in 2010. I found 11 projects for $1.7M in 2009.

I thought it time to revisit this question. I’m using a different data source–the NIH RePORTER database. Because of that these projects are those funded by NIH. Other Federal groups can and do fund autism research. Also private organizations like Autism Speaks

Below are the projects I found for the past few years. There are projects on epidemiology, treatment and biology.

While I think that the funding agencies could do a better job informing the communities about these projects, I sincerely wish that the parent advocacy groups calling for this research would inform their members that it is going on. I am actually very curious as to why they have not done that.

MECHANISMS OF AUTONOMIC BRAINSTEM DEVELOPMENT ($243,000)

Brainstem and autonomic circuitry, though understudied in neurodevelopmental disorders, are implicated in pathophysiology and co-occurring medical conditions, such as gastrointestinal disturbances (GID). The goal of this R21 project is to fill this knowledge gap, based on significant preliminary data.

CASEIN KINASE 1 INHIBITORS FOR TREATMENT OF AUTISM $349,610

The overall goal of our program is to (1) identify CK1 [Casein Kinase 1] inhibitors suitable for development as therapeutic agents and (2) to use these agents to investigate the suitability of CK1 inhibitors for addressing specific behavioral features of the complex, multi-symptom disorder known as autism.

The CADDRE SEED studies are multiyear but I haven’t listed all the grants. So the amount is much higher than even the substantial sums noted below.

MD CADDRE: STUDY TO EXPLORE EARLY DEVELOPMENT, SEED PHASE II $91,706

MD CADDRE: STUDY TO EXPLORE EARLY DEVELOPMENT, SEED PHASE II $1,600,000

CALIFORNIA CADDRE-SEED PHASE II $1,100,000

NC CADDRE: STUDY TO EXPLORE EARLY DEVELOPMENT (SEED) PHASE II $1,100,000

COLORADO CADDRE STUDY TO EXPLORE EARLY DEVELOPMENT CADDRE_SEED II $1,100,000

PA-CADDRE: STUDY TO EXPLORE EARLY DEVELOPMENT (SEED) PHASE II $1,100,000

SEED will address hypotheses including: ASD phenotypic variation, including the pattern of clustering of core symptoms, timing of onset, cognitive status, and presence of medical and psychiatric co-morbidities; gastrointestinal features; genetic variation and interaction with environmental risk factors (GxE); infection, immune function, and autoimmunity factors; hormonal factors and maternal reproductive characteristics; and sociodemographic and lifestyle factors.

INVESTIGATING THE GUT MICROBIOME FOR NOVEL THERAPIES AND DIAGNOSTICS FOR AUTISM $558,136 (also funded in 2013 for $558,136)

Based on compelling preliminary evidence, this project aims to explore the potential connection between GI barrier defects and altered behavior in preclinical models of autism. Our long-term goal is to explore possible serum biomarkers for ASD diagnosis, and potentially develop a novel probiotic therapy for at least a subset of children with ASD with GI issues.

2013 projects

TREATMENT OF MEDICAL CONDITIONS AMONG INDIVIDUALS WITH AUTISM SPECTRUM DISORDERS $488,568 (also, $339,591 in 2012, $264,726 in 2011, $578,006 in 2010, $535,209 in 2009, and $465,840 in 2008)

The life-long impairments in communication and social function are often complicated by the presence of medical comorbidities, including epilepsy, (and epileptiform discharges), gastrointestinal disturbances and sleep disorders.

REGULATION OF GASTROINTESTINAL NEUROMUSCULAR FUNCTION BY NIBP/NFKB SIGNALING $320,576 (and 2012 $343,747)

The proposed research is relevant to public health because the discovery of a novel function of NIBP/NFkB signaling in enteric neurons and glial cells is ultimately expected to increase the understanding of the pathogenesis of gastrointestinal diseases. It also shed light on the therapeutics for gastrointestinal inflammation and functional disorders.

ARE AUTISM SPECTRUM DISORDERS ASSOCIATED WITH LEAKY-GUT AT AN EARLY CRITIACAL PER $292,221 (and 2012 $302,820, and 2011 $302,820)

This project seeks to answer fundamental questions about the connection between early development of gastrointestinal (GI) problems (constipation, diarrhea, vomiting, etc.) and autism spectrum disorders (ASD)

From 2011

NEUROIMMUNOLOGIC INVESTIGATIONS OF AUTISM SPECTRUM DISORDERS (ASD) $264,726

A number of anecdotal reports have linked autism with gastrointestinal (GI) dysfunction; most notable among these are reports that autism is associated with “leaky gut” syndrome. Microbial translocation (MT) is the process by which bacteria or microbial byproducts permeate through the wall of the GI Tract (or other abnormally porous mucosal barriers) into the bloodstream. The microbial byproducts would then stimulate the immune system, which could have secondary effects on CNS functioning, or the byproducts could have a direct neurotoxic effect. We conducted assays of MT products in children with autism (from blood and CSF), as well as typically developing children (blood samples only).

and

Our ongoing phenotyping studies will be used to identify a cohort of children with autism who also have significant gastrointestinal symptoms in order to address this potentially important subgroup of patients.

A PRIMATE MODEL OF GUT, IMMUNE, AND CNS RESPONSE TO CHILDHOOD VACCINES $156,634


By Matt Carey

Press Release: Common gene variants account for most genetic risk for autism

23 Jul

This press release is from NIH: Common gene variants account for most genetic risk for autism

Common gene variants account for most genetic risk for autism
Roles of heritability, mutations, environment estimated – NIH-funded study

Most of the genetic risk for autism comes from versions of genes that are common in the population rather than from rare variants or spontaneous glitches, researchers funded by the National Institutes of Health have found. Heritability also outweighed other risk factors in this largest study of its kind to date.

About 52 percent of the risk for autism was traced to common and rare inherited variation, with spontaneous mutations contributing a modest 2.6 percent of the total risk.

nimh-20_l

The bulk of risk, or liability, for autism spectrum disorders (ASD) was traced to inherited variations in the genetic code shared by many people. These and other (unaccounted) factors dwarfed contributions from rare inherited, non-additive and spontaneous (de novo) genetic factors. Source: Population-Based Autism Genetics and Environment Study
“Genetic variation likely accounts for roughly 60 percent of the liability for autism, with common variants comprising the bulk of its genetic architecture,” explained Joseph Buxbaum, Ph.D., of the Icahn School of Medicine at Mount Sinai (ISMMS), New York City. “Although each exerts just a tiny effect individually, these common variations in the genetic code add up to substantial impact, taken together.”

Buxbaum, and colleagues of the Population-Based Autism Genetics and Environment Study (PAGES) Consortium, report on their findings in a unique Swedish sample in the journal Nature Genetics, July 20, 2014.

“Thanks to the boost in statistical power that comes with ample sample size, autism geneticists can now detect common as well as rare genetic variation associated with risk,” said Thomas R. Insel, M.D., director of the NIH’s National Institute of Mental Health (NIMH). “Knowing the nature of the genetic risk will reveal clues to the molecular roots of the disorder. Common variation may be more important than we thought.”

Although autism is thought to be caused by an interplay of genetic and other factors, including environmental, consensus on their relative contributions and the outlines of its genetic architecture has remained elusive. Recently, evidence has been mounting that genomes of people with autism are prone to harboring rare mutations, often spontaneous, that exert strong effects and can largely account for particular cases of disease.

More challenging is to gauge the collective impact on autism risk of numerous variations in the genetic code shared by most people, which are individually much subtler in effect. Limitations of sample size and composition made it difficult to detect these effects and to estimate the relative influence of such common, rare inherited, and rare spontaneous variation.
Differences in methods and statistical models also resulted in sometimes wildly discrepant estimates of autism’s heritability – ranging from 17 to 50 percent.

Meanwhile, recent genome-wide studies of schizophrenia have achieved large enough sample sizes to reveal involvement of well over 100 common gene variants in that disorder. These promise improved understanding of the underlying biology – and even development of risk-scores, which could help predict who might benefit from early interventions to nip psychotic episodes in the bud.

With their new study, autism genetics is beginning to catch up, say the researchers. It was made possible by Sweden’s universal health registry, which allowed investigators to compare a very large sample of about 3,000 people with autism with matched controls. Researchers also brought to bear new statistical methods that allowed them to more reliably sort out the heritability of the disorder. In addition, they were able to compare their results with a parallel study in 1.6 million Swedish families, which took into account data from twins and cousins, and factors like age of the father at birth and parents’ psychiatric history. A best-fit statistical model took form, based mostly on combined effects of multiple genes and non-shared environmental factors.

“This is a different kind of analysis than employed in previous studies,” explained Thomas Lehner, Ph.D., chief of NIMH’s Genomics Research Branch. “Data from genome-wide association studies was used to identify a genetic model instead of focusing just on pinpointing genetic risk factors. The researchers were able to pick from all of the cases of illness within a population-based registry.”

Now that the genetic architecture is better understood, the researchers are identifying specific genetic risk factors detected in the sample, such as deletions and duplications of genetic material and spontaneous mutations. Even though such rare spontaneous mutations accounted for only a small fraction of autism risk, the potentially large effects of these glitches makes them important clues to understanding the molecular underpinnings of the disorder, say the researchers.

“Within a given family, the mutations could be a critical determinant that leads to the manifestation of ASD in a particular family member,” said Buxbaum. “The family may have common variation that puts it at risk, but if there is also a de novo [spontaneous] mutation on top of that, it could push an individual over the edge. So for many families, the interplay between common and spontaneous genetic factors could be the underlying genetic architecture of the disorder.”

Environmental risk factor related research funded by the NIH in 2014

18 Jul

There is a great interest from some in the autism parent community for environmental risk factor research. There is also a belief that this work is not being performed. While the amount of environmental risk factor research is less than the IACC has advised be performed (a point I made in my first IACC meeting), the amount of attention to environmental risk factors has been increasing.

Given this, I thought it would be interesting to see what projects and how many have been funded by the NIH this year (I believe they work on a fiscal year ending Sept. 30, so we have much but not all of the 2014 information available). I used the NIH Reporter website and did a very unscientific search for autism and environment, autism and risk and similar searches.

Below are the funded projects I’ve found. Some are directly on topic. Some more peripherally. And I know I’ve left some out (some on purpose–like Zebrafish studies–and some I missed). I think there are 33 projects below. Something like $20M. Keep in mind, not all Federally funded autism research goes through the NIH and not all autism research is Federally funded.

As I like to point out in these articles, you won’t find this information on the websites of the autism organizations which claim to be focused on environmental risk factor research. In fact, you are more likely to find statements that there is no such research ongoing or it is being blocked.

Here’s a quote from Sallie Bernard of SafeMinds, a quote that was repeated by Congressman Posey at a hearing held last year on autism:

“By ignoring the environmental component to autism, the government and scientific community have made a massive strategic error, wasting enormous amounts of money and time in mostly fruitless genetics-only research that has not helped us stop new cases of autism or helped people living with severe autism”

I think one can argue that more investment should be made. But “ignoring”? I realize that very few people will go to NIH Reporter and search for these projects. But I expect accuracy from those claiming to lead the autism community and acting as though they know the research landscape on autism and the environment.

I was going to ignore the “fruitless” comment above, but I just can’t. I sat on the subgroup writing the IACC’s updates on risk factor research in the Strategic Plan (question 3). As part of that I had the honor of working with some excellent researchers, both on the genetics and the environmental side. If I may be so bold as to relate what I heard in those discussions: I never heard these researchers claim that the genetics research was “fruitless”. Quite the opposite. Was there a strong sense that environmental risk factor research could be better funded? That was certainly my take away. And I agree. My predecessors on the IACC wrote a Plan that called for more research in this area.

That said, I am reminded of my favorite old saying

There’s more politics in science than science in politics.

Except quite frankly, I don’t think the message that environmental risk factor research is being “ignored” and “fruitless” has anything to do with science. It’s just politics.

Here’s that list of funded research (in no particular order):

POPULATION-BASED AUTISM GENETICS & ENVIRONMENT STUDY $655,813

PROSPECTIVE EVALUATION OF AIR POLLUTION, COGNITION, AND AUTISM FROM BIRTH ONWARD $545,679

PESTICIDE EXPOSURE AND CHILDHOOD AUTISM $184,503

PRENATAL TIMING OF HEAVY METAL EXPOSURES FROM AUTISTIC AND NON-AUTISTIC CHILDREN $231,692

MD CADDRE: STUDY TO EXPLORE EARLY DEVELOPMENT, SEED PHASE II $91,706

ANTECEDANTS SEQUELAE OF CHILDHOOD ONSET DISEASE $432,000

MITOCHONDRIAL DYSFUNCTION DUE TO ABERRANT MTOR-REGULATED MITOPHAGY IN AUTISM $183,568

PRENATAL AND NEONATAL BIOLOGIC MARKERS FOR AUTISM $784,863

AUTISM RISK, PRENATAL ENVIRONMENTAL EXPOSURES, AND PATHOPHYSIOLOGIC MARKERS $1,793,611

THE ROLES OF ENVIRONMENTAL RISKS AND GEX IN INCREASING ASD PREVALENCE $537,756

METHYLOMIC AND GENOMIC IMPACTS OF ORGANIC POLLUTANTS IN DUP15Q SYNDROME $341,921

EPIDEMIOLOGICAL RESEARCH ON AUTISM IN JAMAICA – PHASE II $564,795

EARLY PREGNANCY STRESS PROGRAMMING OF OFFSPRING EMOTIONALITY $396,000

GENOME-WIDE IDENTIFICATION OF VARIANTS AFFECTING EARLY HUMAN BRAIN DEVELOPMENT $413,630

EPIGENETIC AND TRANSCRIPTIONAL DYSREGULATION IN AUTISM SPECTRUM DISORDER $531,208

EPIGENETIC INFLUENCE ON THYROID HORMONE ACTION IN THE BRAIN AND ON BEHAVIOR $391,250

MATERNAL ADVERSITY AND EPIGENETIC AND BEHAVIORAL PROGRAMMING ACROSS GENERATIONS $583,246

EXPLORING INTERACTIONS BETWEEN FOLATE AND ENVIRONMENTAL RISK FACTORS FOR AUTISM $118,717

MD CADDRE: STUDY TO EXPLORE EARLY DEVELOPMENT, SEED PHASE II $1,600,000

CALIFORNIA CADDRE-SEED PHASE II $1,100,000

NC CADDRE: STUDY TO EXPLORE EARLY DEVELOPMENT (SEED) PHASE II $1,100,000

COLORADO CADDRE STUDY TO EXPLORE EARLY DEVELOPMENT CADDRE_SEED II $1,100,000

PA-CADDRE: STUDY TO EXPLORE EARLY DEVELOPMENT (SEED) PHASE II $1,100,000

SEX-DEPENDENT MICROGLIAL COLONIZATION AND VULNERABILITY TO A NEONATAL INFECTION $272,270

PRENATAL SEX STEROIDS, BISPHENOL A, PHTHALATES, AND SEXUALLY DIMORPHIC BEHAVIORS $244,996

ENVIRONMENT, IMPRINTING, AND NEURODEVELOPMENT $799,726

IN UTERO ANTIDEPRESSANT EXPOSURES AND RISK FOR AUTISM $348,000

SEX DIFFERENCES IN DEVELOPING MICROGLIA: IMPLICATIONS FOR SYNAPTIC PRUNING $392,500

ARE ENDOCRINE DISRUPTING COMPOUNDS ENVIRONMENTAL RISK FACTORS FOR AUTISM? $237,750

THE EFFECT OF MATERNAL OBESITY AND INFLAMMATION ON NEURONAL AND MICROGLIAL FUNCTI $78,250

TRANSCRIPTIONAL AND EPIGENETIC SIGNATURES OF HUMAN BRAIN DEVELOPMENT AND AUTISM $1,542,279

PROJECT 2: THE IMPACT OF ASSISTED REPRODUCTIVE TECHNOLOGIES ON THE LONG-TERM EPI $266,000

PRENATAL FACTORS AND RISK OF AUTISM IN A FINNISH NATIONAL BIRTH COHORT $579,293

One last note: I don’t see funding for the EARLI network. That strikes me as a shame.


By Matt Carey

Note: I serve as a public member to the IACC but all statements are my own.

Why won’t the government fund vaccine/autism research?

15 Jul

This question gets brought up a lot by some parent advocates. The are informed by groups promoting the idea of vaccine causation that the government is blocking this work. The evidence points strongly away from vaccines as a primary cause of autism, and investment in this area doesn’t seem wise. At least that’s the viewpoint of the majority of parents (including myself), autistics and researchers. But some remain unconvinced and want vaccine/autism research performed. And they are upset that none of this work is being performed.

Here’s a different question: why are the groups who promote the idea that vaccines cause autism failing to inform their members that, yes, indeed vaccine/autism research is being performed?

Or, to put it simply: vaccine/autism research is being performed and it’s being funded by the government. But you wouldn’t know that if you read, say, the Age of Autism blog, Generation Rescue’s website, SafeMinds’ website, or the other groups advocating for this research. If you are interested in vaccine/autism research and you are reading about these projects for the first time here, ask yourself “why have these orgs not informed me of this?”.

As noted here recently, Tom Insel discussed an upcoming vaccine/autism study. Already commissioned, performed and in the publication stage. That announcement was in April. What was the response from the community that has pleaded for vaccine/autism research? For the first few months: Silence. In July, SafeMinds finally put out an article showing that they were “worried” about this study. I don’t see much discussion of this announcement from other groups or outlets.

I’m not surprised by this. I’ve noted before that work on areas such as vaccines, mercury, environmental risk factor research and GI dysfunction don’t get discussed by the groups that are focused on these topics. I’ve covered the research in these areas more than they have.

So let’s get back to what other work is going on in vaccines and autism. Let’s start with the simple question: how would you find out? One place is the IACC/OARC Autism Spectrum Disorder Research Portfolio Analysis Web Tool. That could use updating, but it is an easily searchable database. Another place is NIH Reporter. It’s less easy to use than the Portfolio Analysis Tool and includes all of NIH. I.e. it covers non autism topics and doesn’t include projects being done outside of NIH (say, by Autism Speaks or other private funders). But, search Reporter for autism and vaccines or mercury and what do you get? Quite a number hits. Let’s consider a few.

How about:

There’s a study by Ian Lipkin’s group at Columbia titled: GENE-ENVIRONMENT INTERACTIONS IN AN AUTISM BIRTH COHORT.

There’s a study by Gene Sackett’s group, A PRIMATE MODEL OF GUT, IMMUNE, AND CNS RESPONSE TO CHILDHOOD VACCINES. This appears to be a follow on project to the Laura Hewitson studies that were discussed a great deal online a few years ago.

Isaac Pessah’s group at the UC Davis MIND Institute has a project NEURODEVELOPMENTAL TOXICOLOGY OF AUTISM. Prof. Pessah also had a multiyear project ENVIROMENTAL FACTORS IN THE ETIOLOGY OF AUTISM

Judy Van de Water’s group at UC Davis MIND Institute has a project IMMUNOLOGICAL SUSCEPTIBILITY OF AUTISM.

The Lewin Group study (which I believe is the one mentioned by Tom Insel) STUDY OF HEALTH OUTCOMES IN CHILDREN WITH AUTISM AND THEIR FAMILIES. (Just a note–see how this has been publicly available information for a year?)

There’s the CHARGE study, which is looking at a large array of potential environmental risk factors, including specifically mentioning mercury. THE CHARGE STUDY: CHILDHOOD AUTISM RISKS FROM GENETICS AND THE ENVIRONMENT

Here’s a 2014 grant to Ray Palmer, well known to the groups promoting mercury as a cause of autism, PRENATAL TIMING OF HEAVY METAL EXPOSURES FROM AUTISTIC AND NON-AUTISTIC CHILDREN.

The EPIDEMIOLOGICAL RESEARCH ON AUTISM IN JAMAICA – PHASE II project is continuing (hence the Phase II) and includes work on mercury.

There are more projects. Some I left out because they are older. But I think the point is made and is very clear: vaccine/autism and mercury/autism research are being funded.

And that is without even discussing how research on the biology of autism feeds into all etiological questions. Whether it’s vaccine, genetics or what have you, if you understand the biology, you have a better chance of understanding the cause. (when I searched NIH Reporter with the terms Autism and Immune, I got 25 pages of hits. Sure, not all are on-topic, but that’s 25 pages, 606 topics).

Here are the full abstracts–with emphasis added by me–for the NIH Reporter projects mentioned above.

GENE-ENVIRONMENT INTERACTIONS IN AN AUTISM BIRTH COHORT.

Abstract Text:
Reports of increasing prevalence of autism spectrum disorders (ASDs), a set of highly genetic conditions, are intensifying interest in the role of environmental exposures, including infectious, immune, and toxic factors. Retrospective studies exploring associations between environmental factors and ASDs are compromised by selection bias, small sample sizes, possibly invalid diagnosis, and absence of biologic measures. This prospective study will employ an unselected birth cohort of 75,500 in which cases are ascertained through screening of the entire population, diagnoses established using uniform procedures, extensive histories and clinical data obtained, and biologic samples collected serially throughout pregnancy and early childhood. The application of high throughput laboratory assays to derive maximal information from developmentally-influenced, finite, and nonrenewable biologic samples, and inclusion of early screening and diagnostic assessments, will permit an unprecedented, rich view of the longitudinal trajectory and nascent signs and symptoms of ASDs, facilitate discovery of biomarkers, and afford unique insights into the role of gene:environment interactions in ASD pathogenesis. Specific aims are to: (1) establish the autism Birth Cohort (ABC) through ascertainment of cases of autism spectrum disorder (ASD, N=150-233) and selection of controls (N-1000) from the Norway Mothers and Child (MoBa) cohort; (2) examine biologic pathways that may predispose to ASD, through evaluation of immune, endocrine, and neuroregulatory factors in mothers during early gestation or at birth and in children, at birth or 30 months postnatal; (3) identify environmental factors that may be directly or indirectly associated with ASD, including pre- or postnatal infection, vaccination, very low birth weight or other obstetric risk factors in which infections are implicated, dietary and/or environmental exposure to methylmercury; (4) describe the natural history of clinical, anthropometric, and neurobehavioral features of ASD; and (5) explore genotypic influences that may be directly or indirectly associated with ASD by testing associations of ASD and/or its endophenotypes with family history of autoimmune disease or selected candidate genes, and investigating conditional gene-environment effects using antecedent factors found to influence ASD risk.

NIH Spending Category:
autism; Brain Disorders; Clinical Research; Genetics; Immunization; Mental Health; Mental Retardation (Intellectual and Developmental Disabilities (IDD)); Neurosciences; Pediatric; Prevention; vaccine Related

Project Terms:
autism spectrum disorder; Autistic Disorder; Autoimmune Diseases; base; Biological Assay; Biological Markers; Birth; Candidate Disease Gene; case control; Child; Clinical; Clinical Data; cohort; Cohort Studies; Collaborations; Collection; Confusion; Control Groups; design; Development; Diagnosis; Diagnostic; Discipline of obstetrics; Disease; disorder risk; Drops; early childhood; Endocrine; endophenotype; Environment; Environmental Exposure; Environmental Risk Factor; Epidemic; Epidemiologic Studies; Evaluation; Exposure to; Family history of; gene environment interaction; Genes; Genetic; Hereditary Disease; Immune; immune function; Infection; insight; interest; Investigation; Laboratories; Life; Measles; Measures; member; Mercury; Methylmercury Compounds; Mothers; Mumps; Natural History; Nested Case-Control Study; neurobehavioral; Neurodevelopmental Disorder; Norway; novel; Pathogenesis; Pathway interactions; Phase; Population; postnatal; Pregnancy; prenatal; Prevalence; Procedures; prospective; Prospective Studies; Recording of previous events; Relative (related person); Reporting; Research; Research Design; Retrospective Studies; Risk Factors; Role; Rubella; Sample Size; Sampling; Screening procedure; Selection Bias; Signs and Symptoms; Specimen; Testing; Vaccination; Vaccines; Vacuum; Very Low Birth Weight Infant

A PRIMATE MODEL OF GUT, IMMUNE, AND CNS RESPONSE TO CHILDHOOD VACCINES.

Abstract Text:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject’s principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Diagnoses of childhood developmental disorders involving autism-spectrum symptoms are increasing, estimated to affect 1 in 100 children in the United States. Childhood Vaccines have been hypothesized to be contributory factors to this increase. The childhood vaccine regimen has an experimentally unstudied potential for cumulative and synergistic toxicities and possible immunologic interference to normal development. A prior study developed a primate model to assess neurodevelopmental consequences of the 1994-1999 pediatric thimerosal vaccine regimen (1994-1999). Significant neurodevelopmental deficits were evident for vaccinated animals in survival reflexes and standardized cognitive tests, and exposed animals developed gastrointestinal inflammation associated with focal transmural colitis, lymphoid hyperplasia, and syncytia.

NIH Spending Category:
autism; Brain Disorders; Cancer; Digestive Diseases; Immunization; Lymphoma; Mental Health; Mental Retardation (Intellectual and Developmental Disabilities (IDD)); Pediatric; Rare Diseases; vaccine Related

Project Terms:
Affect; Animals; Autistic Disorder; Child; Childhood; Cognitive; Colitis; cost; Development; developmental disease/disorder; Diagnosis; Funding; gastrointestinal; Giant Cells; Grant; Immune; Immunologics; Inflammation; lymphoid hyperplasia; Modeling; National Center for Research Resources; Neurodevelopmental Deficit; Primates; Principal Investigator; Reflex action; Regimen; Research; Research Infrastructure; Resources; response; Source; Symptoms; Testing; Thimerosal; Toxic effect; United States; United States National Institutes of Health; Vaccinated; Vaccines

NEURODEVELOPMENTAL TOXICOLOGY OF AUTISM

Abstract Text:
The long range goal is to determine if exposure to environmental toxicants early in development contributes to the etiology of neurodevelopmental disorders such as autism. A related goal is to determine whether susceptibility to autoimmune disease increases the neurotoxicity of environmental contaminants and increases the risk for developing disorders such as autism. Understanding how exposure to environmental toxicants may contribute to the etiology of neurodevelopmental disorders is important so that the exposure risks can be identified and minimized. If immune system dysfunction is found to increase the risk of exposure to environmental toxicants, then exposure limits to toxic substances can be lowered, and children with immune system dysfunction who may be at increase risk can be identified and protected. The specific aims are to expose mouse strains with low (C57BL/6J) or high (SJL mice) susceptibility to autoimmunity perinatally to either methylmercury (MeHg), polychlorinated biphenyl 95 (PCB 95) or polybrominated diphenyl ether 47 (BDE 47). We will then compare the effects of toxicant exposure between these mouse strains on brain development, complex social behaviors, and immune system function. The hypothesis is that perinatal exposure to each of these toxic substances will impair brain development and behavior, and that suscepbility to autoimmune disease will increase the neuro- and immunotoxicity of these agents. We will also explore a potentially new model of autism in mice injected prenatally with unique autoantibodies isolated from the serum of mothers who have given birth to two more more autistic children. Brain development will be examined histologically using stereological procedures and immunohistochemistry. Complex social behaviors will be studied using behavioral testing procedures established in our laboratory that measure social recognition, social interaction and social communication in mice. Immune system status will be established by measuring cytokines, chemokines, immunoglobulins, and quantifying immune system response to antigenic stimulation. In addition, seizure susceptibility will be measured in toxicant-exposed mice as well as measures of synaptic excitibility and plasticity in hippocampal brain slices. These studies will provide critical new information on the role of the immune system and its interaction with environmental contaminants in autism and other neurodevelopmental disorders.

NIH Spending Category:
autism; Autoimmune Disease; Behavioral and Social Science; Brain Disorders; Epilepsy; Mental Health; Mental Retardation (Intellectual and Developmental Disabilities (IDD)); Neurodegenerative; Neurosciences; Pediatric; Perinatal Period – Conditions Originating in Perinatal Period

Project Terms:
Age; Animal Testing; Antibodies; Anxiety; autistic Children; Autistic Disorder; Autoantibodies; Autoimmune Diseases; Autoimmune Process; Autoimmunity; Behavior; behavior test; Behavioral; Biological Assay; Birth; Brain; CCL2 gene; CCL3 gene; CCL4 gene; Cerebellum; chemokine; Chemokine (C-C Motif) Ligand 4; Child; Complex; cytokine; density; Development; developmental disease/disorder; developmental neurotoxicity; Disease; Environmental Pollution; Enzyme-Linked Immunosorbent Assay; Etiology; Exposure to; fetal; Fibroblast Growth Factor; Flurothyl; Fright; Glutamate Receptor; Goals; Granulocyte-Macrophage Colony-Stimulating Factor; Hippocampus (Brain); Histologic; Homer 1; human TNF protein; IL8 gene; Immune response; Immune system; Immune System and Related Disorders; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Immunohistochemistry; Immunophilins; immunotoxicity; In Vitro; in vivo; Infection; Interferon Type II; Interleukin-10; Interleukin-17; Interleukin-4; Interleukin-5; Interleukin-6; Kindling (Neurology); Laboratories; Learning; Leptin; link protein; Long-Term Potentiation; Measures; Memory; Metabotropic Glutamate Receptors; Methods; Methylmercury Compounds; Mitogens; Modeling; Mothers; mouse model; Mouse Strains; Mus; N-Methylaspartate; neurobehavioral disorder; neurodevelopment; Neurodevelopmental Disorder; Neurologic; Neuronal Injury; Neurons; neurotoxicity; offspring; Pentylenetetrazole; Perinatal; Perinatal Exposure; phenyl ether; Plasma; Poisons; Polychlorinated Biphenyls; postnatal; Predisposition; pregnant; prenatal; prenatal exposure; Preparation; Principal Investigator; Procedures; programs; Proteins; RANTES; receptor; receptor function; repaired; Research Design; Research Personnel; research study; response; Risk; Role; Ryanodine Receptor Calcium Release Channel; Ryanodine Receptors; Seizures; sensory gating; Sensory Motor Performances; Serological; Serum; Signal Pathway; Signal Transduction; SJL Mouse; SJL/J Mouse; Slice; Small Inducible Cytokine A3; social; Social Behavior; social communication; Social Interaction; Source; Splenocyte; Structure; Synapses; synaptotagmin; System; T-Cell Proliferation; Testing; Tetanus; Tetanus Toxoid; Tetanus vaccine; Toxic Environmental Substances; toxicant; Toxicant exposure; Toxicology; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factors; Western Blotting; Work; Xenobiotics

IMMUNOLOGICAL SUSCEPTIBILITY OF AUTISM.
Abstract Text:
Recent studies indicate that immune function in children with autism spectrum disorder (ASD) is profoundly altered compared to developmentally healthy controls. There is a strong interface between the immune system and the neurologic network, and successful neurodevelopment is contingent upon a successful interaction between these two systems. We have identified several aspects of immune dysfunction in patients with autism compared with typically developing controls. These include a reduced response to vaccine antigens of bacterial origin, altered cytokine levels in plasma and upon stimulation of PBMC, increased levels of leptin in patients with early onset autism, and autoantibodies to brain antigens. This wide and complex variety of immune anomalies noted in our first funding period is in keeping with the broad range of phenotypes encompassed by the autism spectrum. Thus, we will build upon our earlier findings of both serologic and cellular changes in immune function. While our studies in the previous project period were aimed at a broad analysis of immune function in patients with autism, the current proposal will address the mechanisms responsible for the numerous alterations in immune homeostasis uncovered in our earlier studies. Therefore, our primary focus will be on the mechanisms responsible for such anomalies in immune function through an in depth analysis of cellular immune function. Our overall hypothesis is that patients with autism have a fundamental defect at the cellular level that ultimately leads to abnormalities in immune function and heightened susceptibility to environmental triggers. To examine this, we propose to: (1) examine longitudinally the serologic profile of children with ASD to ascertain whether the various immune changes noted in our first studies are maintained and/or deteriorating further; (2) determine which immune cell population(s) plays a critical role in the immune dysfunction seen in patients with autism; and (3) fully characterize the autoantibody response in a subpopulation of children with ASD and some mothers of children with ASD. It must be noted that due to the highly heterogeneous nature of autism, there will potentially be immunologic differences that relate to sub-groups of patients with autism. Therefore, we will carefully define the study groups based on our current data to include children with early onset autism, children with delayed onset/regressive autism, general population controls, and children with developmental disorders without ASD. The studies will be performed on CHARGE subjects formerly analyzed by our laboratory (CHARGE-BACK study). This will allow us to extend our prior studies longitudinally to determine if the immune dysregulation, such as increased leptin levels in the early onset patients, remains over time. The following aims address both the serologic and cellular aspects of immune function in patients with autism.

NIH Spending Category:
autism; Brain Disorders; Mental Health; Mental Retardation (Intellectual and Developmental Disabilities (IDD)); Neurosciences; Pediatric

Project Terms:
Address; Age; anti-IgM; Antibodies; Antigens; autism spectrum disorder; autistic Children; Autistic Disorder; Autoantibodies; B-Lymphocytes; Back; base; Behavior; Blood Cells; Brain; calcium indicator; Calcium Signaling; Cell Culture Techniques; Cell physiology; Cell Proliferation; Cell surface; Cells; Child; Color; Complex; Cultured Cells; cytokine; Data; Defect; Development; developmental disease/disorder; Digestion; Disease; Dose; Dyes; early onset; Environmental Health; Etiology; fetal; Flow Cytometry; Flu virus; Frequencies (time pattern); Funding; Gel; General Population; HLA-DR Antigens; Homeostasis; Human; IgE; Immune; immune function; Immune system; Immune System Diseases; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunologics; Label; Laboratories; Lasers; Leptin; Maps; Mercury; Microarray Analysis; Mitogens; Modeling; Mothers; Mus; Nature; neurodevelopment; Neurologic; Oligonucleotides; Pathogenesis; Pathology; Patients; Pattern; Peptides; Peripheral Blood Mononuclear Cell; Phenotype; Plasma; Play; Poly I-C; Population; Population Control; Predisposition; Pregnancy; Principal Investigator; Production; programs; Reagent; research study; response; RNA; Role; Serological; Serum; Source; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Staining method; Stains; System; T-Lymphocyte; Testing; Time; TNFSF5 gene; Tube; Up-Regulation (Physiology); Upper arm; vaccine Antigen; Xenobiotics

STUDY OF HEALTH OUTCOMES IN CHILDREN WITH AUTISM AND THEIR FAMILIES

Abstract Text:
This contract modification is to extend and supplement Contract HHSN271201000033C, consistent with the scope of work of “Study of Health Outcomes in Children with autism and Their Families¿ in order to access the currently validated database developed under the contract to provide for further analysis . Autism Spectrum Disorder (ASD) is a significant public health concern, with an estimated prevalence of 1 in 88 children in the United States. Much of the research to date has focused on the core social and communication deficits of ASD, but there are anecdotes and some survey data suggesting that the rate of comorbid health conditions may also be elevated in this population. Furthermore, despite several large-scale epidemiological studies that have assessed but not found any potential association between ASD and vaccinations, public concerns persist about such a causal link. At least partly as a consequence, health officials in the United States have reported an increased rate of vaccine refusal in the general population. The Study of Health Outcomes in Children with autism and their Families was begun two years ago. Under this contract, the Contractor analyzed a large dataset of retrospective commercial health plan claims of 46,236 children with ASD, their parents and siblings, and a comparison cohort of children and family members. They successfully completed the analyses requested in the original statement of work, which included a study of the validity of ASD diagnoses in the claims data, and descriptions of health outcomes and health care utilization of the ASD cohort, their family members, and the comparison cohorts.

NIH Spending Category:
autism; Brain Disorders; Immunization; Intellectual and Developmental Disabilities (IDD); Mental Health; Pediatric; Prevention; vaccine Related

Project Terms:
Anecdotes; autism spectrum disorder; Autistic Disorder; Child; cohort; Contractor; Contracts; Data; Data Set; Databases; Diagnosis; Epidemiologic Studies; Family; Family member; General Population; Health; health care service utilization; Health Planning; Link; Modification; Outcome; Parents; Population; Prevalence; public health medicine (field); Recording of previous events; Reporting; Research; Siblings; social communication; Surveys; United States; Vaccination; Vaccines; Work

CORE D: MOLECULAR GENOMICS CORE

Core 4 is the Molecular Core. It serves as the central resource for the projects that isolate and process RNA on Affymetrix microarrays, and for performing RT-PCR confirmation of the microarray data for those projects. The UCD Affymetrix Core Facility is run by Dr. Jeffrey Gregg and is equipped with fluidics stations, hybridization ovens, and the new scanner required to scan the human Affymetrix U133 2.0PLUS arrays. Preliminary data from the previous CHARGE study has shown that there are changes in gene expression in the blood of children with autism compared to control children in the general population (GP) and to control children with mental retardation and developmental delay (MR/DD). The blood genomic profile in children with autism without regression (A) was different from controls, autism spectrum disorder (ASD) and different from children with autism with regression (A-R). In addition, there is a group of regulated genes in most children with A, A-R and with ASD that are expressed by natural killer (NK) cells in peripheral blood, suggesting an abnormality in this cell type that is common to all types of autism. These NK-cell related genes are expressed by all of the autism phenotypes including A, A-R and ASD, and hence may point to common pathways that underlie the common language and behavioral abnormalities in all three disorders. This core will be utilized by the projects as follows. Project #1: Aim #1: Perform genomic (RNA expression on microarrays) studies on blood from children with autism in the 4-9 year old range, and compare to the blood genomic profiles we have obtained in children with autism in the 2-5 year old age range. Aim #2. Compare gene expression as a function of blood metal levels in both age groups in A, A-R, ASD, MR/DD and GP groups. Aim #3. Examine genomic profiles in pregnant mothers who have previously given birth to an autistic child to determine if there is a specific genomic profile that correlates with whether the mother’s fetus is destined to develop autism. Project #2. Aim #1. Describe the gene expression profiles in the blood using specific white blood cell subsets including NK cells for children with autism without regression, autism with regression, and ASD children compared to GP and delayed children. Aim #2. Examine gene expression following stimulation or activation of specific white blood cell subsets of A, A-R, ASD, MR/DD and GP children with: low level mercury; immune cell stimulation/activation with vaccine antigens and cell-specific mitogens; and xenobiotics. Project #3. Compare gene expression profiles in the blood of children with autism to the blood of experimental animals exposed to toxicants including organic mercury, PCB 95, and PBDE 47 (Project #3).

NIH Spending Category:
autism; Biotechnology; Brain Disorders; Genetics; Mental Health; Mental Retardation (Intellectual and Developmental Disabilities (IDD)); Pediatric

Project Terms:
5 year old; 9 year old; Accounting; Age; age group; Animals; autism spectrum disorder; autistic Children; Autistic Disorder; Autoantibodies; base; Behavioral; Birth; Blood; Blood specimen; cell type; Cells; chemokine; Child; Core Facility; cytokine; Data; Developmental Delay Disorders; Disease; Environmental Health; Fetus; Gene Expression; General Population; Genes; Genetic; Genetic Transcription; Genome; Genomics; Human; Immune; immune function; Inherited; Language; Leukocytes; Mental Retardation; Mentally Disabled Persons; Mercury; Metals; Mitogens; Molecular; Molecular Profiling; Mothers; Natural Killer Cells; Pathway interactions; Patients; pentabromodiphenyl ether; peripheral blood; Phenotype; Polychlorinated Biphenyls; Population Group; pregnant; Principal Investigator; Process; programs; Resources; Reverse Transcriptase Polymerase Chain Reaction; RNA Processing; Running; Scanning; Subgroup; Surveys; Toxic Environmental Substances; toxicant; vaccine Antigen; Xenobiotics

THE CHARGE STUDY: CHILDHOOD AUTISM RISKS FROM GENETICS AND THE ENVIRONMENT

Abstract Text:
DESCRIPTION (provided by applicant): Few rigorous epidemiologic studies have addressed the environmental causes and biologic underpinnings of autism spectrum disorder (ASD). The CHARGE (Childhood autism Risks from Genetics and Environment) Study is a large, population-based case-control investigation of environmental risk factors, broadly defined, in relation to ASD and developmental delay without ASD symptoms, with referents from the general population. Fieldwork began in 2003, and by now CHARGE has published widely on exposures such as air pollution, mercury, flame retardants, maternal nutritional status in the peri-conception, untreated fever during pregnancy, mitochondrial dysfunction, candidate genes, a wide array of functional immune markers in both the child and the mother, and maternal metabolic conditions including obesity and diabetes. This last finding is notable, given the epidemic of obesity and type 2 diabetes that has occurred in parallel with the steady rise in ASD over the last few decades. Moreover, an emerging literature implicates several endocrine disrupting chemicals as contributing to obesity and metabolic dysregulation, including hyperinsulinemia, and to neurodevelopmental disorders as well. This project therefore builds upon these observations in several ways. First, obesity and type 2 or gestational diabetes will be examined in a larger sample, and glucose challenge test (GCT) results for the first time, to determine associations not only with development of ASD and intellectual impairment in the children, but also with specific speech and language delays, behavioral phenotypes such as attention deficits or hyperactivity, and gene expression. Second, these maternal metabolic conditions will be evaluated for associations with markers of both metabolic and immune dysregulation to be measured in neonatal bloodspots. Third, the predictive value of neonatal bloodspot markers for a later diagnosis of ASD or other child developmental and behavioral outcomes will be assessed. Fourth, the maternal metabolic conditions will be analyzed for potential links with upstream exposures to phthalates and anti- bacterial compounds, ubiquitous chemicals in common household products. Finally, this project will examine how gene variants that play a role in biochemical pathways relevant to the processes under study may influence susceptibility of the mother, the neonate or the child. To ensure adequate power for this analysis of gene-environment interaction, the sample size will be increased to 2400 children. This project addresses several goals set by the NIH Interagency autism Coordinating Committee: 1) to discover environmental factors contributing to ASD, particularly in the prenatal period, 2) to understand biological mechanisms for ASD risk, including gene-by-environment interactions, and 3) to identify children at risk for ASD at earlier time points. Results of this detailed inquir into early exposures, maternal pathophysiology and prognostic markers in the newborn will set the stage for developing prevention strategies.

Public Health Relevance Statement:
PUBLIC HEALTH RELEVANCE: This project addresses several issues of direct public health relevance, and the science to be produced will lead to benefits in a wide cross-section of the U.S. population. Because obesity is reaching epidemic proportions and other metabolic conditions such as Type 2 diabetes, gestational diabetes, and dyslipidemia are rising steeply, understanding environmental causes has tremendous public health potential for moving us closer to effective prevention strategies. If environmental chemicals used in common household products do prove to adversely affect body weight, measures can be taken to either reformulate those products, removing them from the market, or to educate consumers on how to avoid them. Similarly, steady increases in ASD might be curbed if the postulated causal pathway is supported by the evidence.

NIH Spending Category:
autism; Behavioral and Social Science; Brain Disorders; Clinical Research; Diabetes; Genetic Testing; Genetics; Intellectual and Developmental Disabilities (IDD); Mental Health; Neurosciences; Nutrition; Obesity; Pediatric; Perinatal Period – Conditions Originating in Perinatal Period; Prevention

Project Terms:
Address; Affect; Age; aged; Air Pollution; Anti-Bacterial Agents; Attention; autism spectrum disorder; Autistic Disorder; Behavior; Behavioral; Biochemical Pathway; Biological; Biological Markers; blood glucose regulation; Body Weights and Measures; C-Peptide; Candidate Disease Gene; case control; CCL2 gene; chemical association; Chemicals; Child; Childhood; Conceptions; cytokine; Data; Development; Developmental Delay Disorders; Diabetes Mellitus; Diagnosis; disorder risk; Dyslipidemias; Endocrine Disruptors; Ensure; Environment; environmental chemical; Environmental Risk Factor; Epidemic; Epidemiologic Studies; ESR1 gene; Exposure to; Fever; Flame Retardants; Functional disorder; gene environment interaction; Gene Expression; General Population; Genes; Genetic Risk; Gestational Diabetes; Glucose; glucose metabolism; Goals; high risk; Household; Household Products; human TNF protein; Hyperactive behavior; Hyperinsulinism; Hypertension induced by pregnancy; Immune; immune function; Immunologic Markers; Impairment; inattention; Inflammation; Inflammatory; Insulin Resistance; insulin sensitivity; interest; Interleukin-6; Investigation; Language Delays; Lead; Leptin; Link; Literature; Marketing; Maternal Exposure; Measures; mercury; Metabolic; Metabolic Marker; Metabolism; mitochondrial dysfunction; Mothers; Neonatal; neonate; neurodevelopment; Neurodevelopmental Disorder; Newborn Infant; Non-Insulin-Dependent Diabetes Mellitus; Nutritional status; Obesity; Outcome; Pathway interactions; Phenotype; phthalates; Play; Population; population based; PPARG gene; Predictive Value; Predisposition; Pregnancy; prenatal; Prevention strategy; Process; prognostic; Prognostic Marker; public health medicine (field); public health relevance; Publishing; Regulation; Risk; Role; RORA gene; RPL10 gene; Sample Size; Sampling; Science; Self Care; Speech Delay; Staging; Symptoms; Test Result; Time; Triclosan; Tumor Necrosis Factor-alpha; United States National Institutes of Health; Variant; Variation (Genetics)

PRENATAL TIMING OF HEAVY METAL EXPOSURES FROM AUTISTIC AND NON-AUTISTIC CHILDREN

DESCRIPTION (provided by applicant): Little is known about the etiology or risk factors for autism, a disease affecting 1 in 50 children in the U.S. While genetic and environmental factors are thought to act together, the specific mechanisms are not known and the measurement of environmental risk factors during critical periods of neurodevelopment has been lacking. This case-control study seeks to apply a novel dental biomarker of early life metal exposure, including in utero, to identify risk factors for ASD. Beyond looking at exposure intensity, we will be able to identify differences in exposure timing between cases and controls. This will allow us to identify critical windows when exposure, even at low levels, increases the risk of ASD. Using the proposed biomarker, we will directly assess fetal exposure, and will not rely on maternal biomarkers which may only provide an indirect measure of fetal exposure to metals. This work will have substantial impact on epidemiologic investigations of the relation of early life chemical exposures to ASD and other neurodevelopmental disorders as it can be used to objectively reconstruct both exposure intensity and timing.

Public Health Relevance Statement:
PUBLIC HEALTH RELEVANCE: Little is known about the causes of autism. This proposal seeks to apply a novel dental biomarker of early life metal exposure, including in utero, to identify risk factors for ASD. Beyond looking at exposure intensity, our application is novel in that we will be able to identify differences in exposure timing between cases and controls. This will allow us to identify critical windows when exposure, even at low levels, increases the risk of ASD.

Project Terms:
Accounting; Address; Affect; Aluminum; analytical method; Animals; Apatites; Arsenic; autism spectrum disorder; autistic Children; Autistic Disorder; Binding (Molecular Function); Biological; Biological Markers; bone; Cadmium; Calcified; Calcium; case control; Case-Control Studies; Chemical Exposure; Chemicals; Child; Childhood; Chromium; critical period; Data; deciduous tooth; Dental; Dentin; Development; Disease; early life exposure; Elements; Environment; Environmental Exposure; Environmental Risk Factor; Epidemic; Epidemiologic Studies; Etiology; Exposure to; fetal; Fetus; Genes; Genetic; Health; Heavy Metals; Human; Immune system; in utero; Investigation; Lead; Life; Literature; longitudinal design; Manganese; Measurement; Measures; mercury; Metal exposure; Metals; Methodology; Methods; mineralization; Mothers; neurodevelopment; Neurodevelopmental Disorder; Nickel; novel; Perinatal; Perinatal Exposure; Play; postnatal; Predisposition; Pregnancy; prenatal; Property; prospective; public health relevance; Recording of previous events; repository; Risk; Risk Factors; Role; Sampling; skeletal; Staging; Time; Tissues; Tooth structure; Toxic Environmental Substances; toxicant; Toxicant exposure; Work

A study comparing vaccinated and unvaccinated kids is coming…and SafeMinds is concerned

10 Jul

If a discussion of autism goes on long enough in the online parent community, the question of vaccines will almost certainly come up. (I’ll note that in real life it rarely, almost never, comes up). If the vaccine topic takes over the discussion, one is very likely to hear the call for a “vaxed/unvaxed” study: a comparison of health outcomes for kids who were vaccinated compared to kids who were not vaccinated.

There are at least three such studies in the works. Two are being funded by groups antagonistic to vaccines. The self-named “National Vaccine Information Center” is funding a project at George Mason University. Said study is, I believe, run by someone from NVIC. Generation Rescue is funding a project at Jackson State University, “Researching into the causes of autism”. In previous years, Generation Rescue was funding Jackson State for a project “vaccination status and health outcomes among homeschool children in the United States”, which is likely the same project just with a different name. Perhaps that’s the same study that the founder of “Focus Autism” is complaining about here. Either way, there are two, maybe more, vaccinated/unvaccinated studies that have been underway for a few years, funded by groups generally antagonistic towards vaccines.

As an aside–in online discussions, the people calling for a vaxed/unvaxed study are connected to Generation Rescue and NVIC. And yet they act like no one is doing such a study.

Back to the topic at hand: there is another vaccinated/unvaccinated study in the works. A large study. In discussions at an IACC meeting this year, Tom Insel responded to a statement about a vaccinated vs. unvaccinated study:

Dr. Insel: So I might add, we have just done that study looking at, in this case, tens of thousands of children in a large health care system — younger siblings, many of whom did not vaccinated. So we could, whether you like it or not, compare what the risks are, both the risk for autism and the risks for medical consequences for not being vaccinated versus being vaccinated in children who have presumably some genetic risk because they’re young sibs.

And those data are submitted for peer review. We should — maybe by July we’d be able to have that presented here. So I’ll be happy to, since we’ve funded that through, be happy to ask the authors to come and talk to us about the results.

That statement was in April. We just had the July IACC meeting but the results were not presented. The study is in the works, though. At the time Dr. Insel made that statement it struck me that this study was likely a part of a project by the Lewin Group. The Lewin Group presented at the IACC in early 2013. That project has not yet been published, but the results presented last year were very interesting, so I’ll take some time to go through those results here. Keep in mind that it’s possible the upcoming vaccinated/unvaccinated study is not by the Lewin Group.

The Lewin Group study population was large and included a large cohort of siblings of ASD kids:

lewin1

When I read or hear “comorbid conditions” discussed by advocacy groups or parents, they are almost always those conditions which those groups feel are part of their “vaccines cause autism” picture. Gastrointestinal complaints–falsely linked by Andrew Wakefield to the MMR vaccine and autism. Mitochondrial/metabolic disorders, brought to prominence by a famous vaccine court case.

Yes, in this study metabolic dysfunction and gastronintestinal/nutritional conditions are about 4.5 times more common in ASD kids. About 20% of kids are in the gastronintestinal/nutritional conditions group (I wonder how that breaks down into GI and nutritional as separate groups). About 5% have metabolic conditions.

But what if I were to tell you that these are not the most common comorbid conditions in ASD children (and ASD adults are yet another story)? Not by a long shot.

lewin2

About 70% of ASD kids have neurological disorders. About 70% have mental health conditions.

70%. 24 times higher than the general population for each condition.

You just don’t hear that from groups promoting vaccine causation. Groups like SafeMinds. Which brings us back to the vaccinated/unvaccinated study SafeMinds is concerned about. SafeMinds is preparing its readers for the vaccinated/unvaccinated study. Although they’ve been calling for this study for a long time, a fact they remind us of this fact in their article: The NIH is slated to release the results of a study on autism in vaccinated, partially vaccinated, and non-vaccinated children. Here’s what you need to know BEFORE it comes out.

SafeMinds begins their article comes with what I consider a rather ironic graphic:

SafeMindsBlowsAnIronyMeter

Why is this ironic? SafeMinds relies upon poorly done research to support their arguments about vaccines, mercury and autism. For example, their non-peer reviewed Autism: A Novel Form of Mercury Poisoning is one of the papers that first made me question the purported vaccine/autism link. It was never very good and really should be discarded. As another example, if you go the SafeMinds web page
Correlation Between Increases in Autism Prevalence and Introduction of New Vaccines you will find this graph:

california-autism-prevalence

If you think that graph looks old, you’d be correct. It’s at least 10, if not 15 years old. It takes California Department of Developmental Services (CDDS) administrative data, pretends it’s actually autism prevalence, and graphs it against the mercury exposure from infant vaccines during the 1990’s and leads the reader to the idea that mercury exposure and autism are correlated and also related. But they aren’t correlated. That’s what happens when you use a 15 year old graph. California removed thimerosal from infant vaccines, even the flu shots, and also for vaccines for pregnant women. And what happened to the autism rate? It kept going up. Schechter and Grether published this in 2008 in Continuing increases in autism reported to California’s developmental services system: mercury in retrograde. In 2013, I showed that the increase was still going on. But SafeMinds is acting like the last decade didn’t happen. They tell us:

Autism prevalence increased rapidly in the late 1980s. The epidemic increased simultaneously in states across the United States, indicating that U.S. children were exposed to toxins in a consistent manner across the entire country. Due to the high adherence amongst the states to the CDC-recommended vaccination schedule, vaccines typically introduce a new exposure to children simultaneously throughout the country.

For people who actually looked at the CDDS data, we know the idea that autism was rising in the same way in various locations wasn’t true. The whole basis for a universal exposure causing the rise in identified autism was false. It’s one of those facts that made me question the vaccine hypothesis long ago. CDDS data even in 2000 showed autism rates varied wildly across the state of California and the increase was not the same from region to region within the state. Special Ed data (which has major limitations but is likely the data SafeMinds was using to make the above statement) showed large variation from state to state in the number of people getting services under the autism label. There is not and never was data to support the assertion SafeMinds makes above that the rates of autism increased simultaneously across the US.

All this is my long-winded way of saying, I find it more than ironic that SafeMinds wants to warn me about flawed research leading to bad conclusions.

So, let’s ask ourselves: why would SafeMinds be concerned enough about this new vaccinated/unvaccinated study? Well, siblings of autistic kids are (a) more likely to be unvaccinated and (b) more likely to be autistic, like 20 times more likely to be autistic (here and here)

The Lewin group reported that younger siblings were less likely to be vaccinated:

lewin3

In addtion, an unpublished study from 2011 compared vaccination status among ASD kids, their siblings and non-relatives. The authors found:

Instead, because siblings of children with autism were less likely to be vaccinated according to the recommended schedule, both correlations and multiple regressions revealed a significant relationship between higher rates of vaccination and non-ASD behavioral outcomes.

Or, to put it simply, if you look at younger siblings, they get fewer vaccines than the general public and have a higher rate of autism. If correlation is causation, this would mean that vaccines prevent autism. Which, in at least one case, is true. Correlation is not causation, though. The new study will likely find that delaying or forgoing vaccines does not reduce autism risk. And that, in my view, would concern SafeMinds. Enough that they want people prepared in advance for what to them will be “bad” news.


By Matt Carey

HHS Announces Appointment of New Public Members to the Interagency Autism Coordinating Committee

2 Jul

The U.S. Interagency Autism Coordinating Committee (IACC) will have two new members when it meets next week. The press release is below. The new members are Wendy Chung from Simons Foundation and Robert Ring from Autism Speaks. The Simons Foundation is the largest non-governmental funder of autism research and previously had a member on the IACC (Dennis Choi). My understanding is that Mr. Choi took a position working with a foreign government and that conflict required him to resign the IACC. Geri Dawson is still on the IACC and started this session working for Autism Speaks. Ms. Dawson has since left Autism Speaks.

For Immediate Release
July 2, 2014

HHS Announces Appointment of New Public Members to the Interagency Autism Coordinating Committee

The Department of Health and Human Services today announced the appointments of Wendy Chung, M.D., Ph.D., and Robert Ring, Ph.D., as public members of the Interagency Autism Coordinating Committee (IACC), a federal advisory Committee composed of federal agency officials and appointed community stakeholders that provides coordination and a forum for public input on issues related to autism spectrum disorder (ASD). Prior to her departure, former HHS Secretary Kathleen Sebelius appointed Dr. Chung, Director of Clinical Research for the Simons Foundation Autism Research Initiative (SFARI), and Dr. Ring, Chief Science Officer of Autism Speaks, to join the IACC in order to provide additional perspectives and expertise to the Committee. Dr. Chung and Dr. Ring serve as leaders within the two organizations that are the largest private funders of autism research in the United States. Both organizations were previously represented on the Committee by individuals who were appointed in 2012, but who have since left or changed affiliation.

Dr. Insel, Chair of the IACC and Director of the National Institute of Mental Health, welcomed the expertise and dedication that Dr. Chung and Dr. Ring bring to the IACC. “Both Dr. Ring and Dr. Chung will be important additions to the Committee, given the depth of their scientific and clinical experience, and their dedication to improving the lives of people on the autism spectrum,” he said.

Dr. Chung, in addition to directing clinical research at SFARI, served as a member of SFARI’s scientific advisory board. Dr. Chung is also the Herbert Irving Associate Professor of Pediatrics and Medicine and Director of Clinical Genetics at Columbia University College of Physicians and Surgeons, where she is the principal investigator for the Simons Variation in Individuals Project (Simons VIP), funded by the Simons Foundation.

Dr. Ring, who has been the Chief Science Officer of Autism Speaks since 2013, also serves as the Chairman of the Board of Delivering Scientific Innovation for Autism (DELSIA), the venture philanthropy arm of Autism Speaks, and leads Autism Speaks’ collaboration with the Simons Foundation to launch the Autism BrainNet, a privately-funded multisite brain banking effort focused on supporting autism research. Dr. Ring previously served as Autism Speaks’ Vice President of Translational Research. He holds adjunct faculty appointments in the Departments of Psychiatry at Mount Sinai School of Medicine and Pharmacology and Physiology at Drexel University College of Medicine. Prior to his work at Autism Speaks, Dr. Ring served as Senior Director and Head of the Autism Research Unit at Pfizer Worldwide Research and Development and worked in the area of psychiatric drug discovery at Wyeth Research.

These two new members of the Committee will serve for the remaining months of IACC activity under the Combating Autism Reauthorization Act of 2011, which will expire on September 30, 2014. If reauthorized, the IACC will be open for nominations of new potential public members in late 2014.


By Matt Carey

Same old Jenny

27 Jun

Jenny McCarthy is back in the news. It appears that The View is not renewing her contract. In fact, there seems to be quite a shakeup at The View with many people leaving.

Jenny McCarthy is responding to this news, discussing fellow View host Sherri Shephard as picked up by Fox News.

“If Sherri goes … I go too,” McCarthy tweeted Thursday from her verified account, adding “#sisters,” followed by another tweet: “My View will be changing too. As will with many hard working folks. Thanks to everyone at the show for your dedication and an amazing year.”

Interesting spin there–instead of being released, she’s framing it as Jenny McCarthy, ready to take a stand and quit her job for her “sister”. Right. One thing I’ve learned over the years watching Jenny McCarthy, she’s good at spinning things to make herself look good.

She’s been a bit of a chameleon when it comes to her opinions. When it comes to autism, she started out with a new-age type “indigo child” approach. Then she took on the “vaccines cause autism” thing, which really catapulted her back into the public eye. Then the vaccine thing became a liability and she got quiet, finally posting an op-ed distancing herself from her previous views*. And, now, we see that the “View” she’s had for the past year was, well, just for “The View”. New job, new View. Will that involve autism, vaccines or something new? We don’t know. We just know that leaving the show means she can change her views.

Same old Jenny.


By Matt Carey

*Jenny McCarthy in her op-ed:
“I’ve never told anyone to not vaccinate.”

I don’t know if that’s true or not. I know she fueled a movement away from vaccines. For example, she wrote on Oprah Winfrey’s website in 2007, “But if I had another child, I would not vaccinate.” Yep, she has technical truth. She didn’t say, “you don’t vaccinate”. She just put herself out there as a leader of a community and said, “I won’t vaccinate”.

You know what word you won’t find in her Op-Ed? Autism. She doesn’t even approach the question that made her famous and that put so much fear in parents. It’s a very politically crafted article, in my opinion.

Jenny McCarthy on Larry King Live:

We’re scared. I mean moms and pregnant women are coming up to me on the street going, I don’t know what to do. I don’t know what to do. And I don’t know what to tell them, because I am surely not going to tell anyone to vaccinate. But if I had another child, there’s no way in hell.

She won’t tell someone *not* to vaccinate, but she “surely” won’t tell some one to vaccinate.

And later on Larry King Live

KING: Isn’t the problem here, Jenny, that people sometimes listen with one ear are going to panic. And not vaccine at all?

MCCARTHY: Probably. But guess what? It’s not my fault. The reason why they’re not vaccinating is because the vaccines are not safe. Make a better product and then parents will vaccinate.

Right. She gives people incorrect information about the safety of vaccines, they get scared and don’t vaccinate, but it’s not her fault because she’s on record saying (but not acting) she’s pro vaccine.

Another time on Larry King Live

MCCARTHY: We get that they’re saving lives, but the increase is ridiculous, you guys. Look, it’s plain and simple. It’s bull (EXPLETIVE DELETED).

KARP: No, it’s not.

MCCARTHY: Too many shots too soon.

(CROSS TALK)

MCCARTHY: My son died in front of me due to a vaccine injury. And there are many — every week I get a picture of a dead child.

KING: You lost a son?

MCCARTHY: Evan died in front of me for two minutes, cardiac arrest. Every week, I get a picture sent to me of a child that died following a vaccination.

What are parents supposed to think when they hear her say that vaccines kill, and that there are “too many, too soon”? Seriously, if there are “too many” vaccines, are parents supposed to say, “Jenny McCarthy is pro-vaccine. I’ll vaccinate my kid!” Too many means some vaccines shouldn’t be given which means, don’t vaccinate with those vaccines.

But, Jenny McCarthy doesn’t want you to think that’s what she said.

Small groups band together to attempt to derail autism research funding

21 May

The law that sets in place the structure to steer autism research is up for renewal this year. Public Law 109-406 was introduced as The Combating Autism Act in 2006. It was reauthorized in 2011. And it is up for reauthorization again this year.

The law authorizes congress to appropriate $190,000,000 per year for autism research. But there are those who would like to scuttle this effort.

A number of groups have banded together to form the “Autism Policy Reform Coalition” to oppose continuing with the law funding autism research. From The Hill:

But an upstart group known as the Autism Policy Reform Coalition (APRC) is against the bill, arguing a drastic overhaul is needed in order for the money to be used effectively.

Who are the “Autism Policy Reform Coalition”? Readers to Left Brain/Right Brain will likely recognize many of these groups. And quickly put together the link that ties them together. In case you haven’t already guess it, yes, it’s vaccines. With science against them on vaccines, they are trying to legislate their views into existence.

Many of these groups are very small. Well funded, but small. None has a truly large membership. Most if not all do not allow for their leadership to be selected by a vote of membership. In fact, for most it seems one can not join them as a member, so it’s difficult to understand how they claim to represent a large part of the autism communities. As far as I know, none have an autistic in any prominent position, much less as a leader. And yet they purport to represent the “autism community”.

While many of these groups have toned down their public statements on vaccines over the years, they are still heavily invested in the idea. One marker of their support for the idea and their lack of scientific rigor is their support for Andrew Wakefield. Mr. Wakefield is the disgraced former academic surgeon who lost his medical license for unethical behavior and whose work attempting to link the MMR vaccine with autism was declared one of the great science frauds by Time Magazine. Much more, his work has been shown to be wrong (for one example, here).

Here are the groups in the Autism Policy Coalition:

Autism is Medical

Appears to be involved with Andrew Wakefield and the failed vaccine-causation notion. They are relatively new having just received 501(c)(3) status this year.

Defending Academic Integrity and Research Foundation
Again, a new group. They appear to be in place in large part to give financial assistance to Andrew Wakefield’s lawsuit against Brian Deer and the BMJ (replacing the “Doctor Wakefield Justice Fund”).

Here’s a recent Facebook page post

D.A.I.R. Foundation is committed to integrity in academics and research and exists to support scientists, doctors, and researchers working in the best interest of the public health whose efforts have come under intense and unfair scrutiny.

At the heart of this is Dr. Andy Wakefield whose work challenged special interest groups who responded with opposition and injustice. The Weston A Price Foundation awarded Dr. Wakefield the prestigious Integrity in Science award at the 2013 Wise Traditions Conference where he was also keynote speaker at the banquet. The DAIR Foundation Fundraiser seeks to provide legal support for Dr Wakefield and others in similar situations. We welcome your support. Tickets are tax deductible and attendees receive cocktails, dinner from a Paleo-style buffet, and a copy of Dr Wakefield’s latest book. Dr. Wakefield will speak to dinner guests about his research and his documentary movie.

To purchase tickets visit the DAIR Foundation website and click on the envelope icon next to the text Orlando Fundraiser Event

It is unclear how one would become a member, voting or not, of DAIR, nor how their leadership is selected.

Generation Rescue

Generation Rescue is currently run by Jenny McCarthy, who has been very vocal in her support of the vaccine/autism link. When Andrew Wakefield lost his job at Thoughtful House, Generation Rescue stepped up with a $100,000 donation to his “Strategic Autism Initiative”.

Generation Rescue’s founder wrote:

With less than a half-dozen full-time activists, annual budgets of six figures or less, and umpteen thousand courageous, undaunted, and selfless volunteer parents, our community, held together with duct tape and bailing wire, is in the early to middle stages of bringing the U.S. vaccine program to its knees.

I can not find from their website whether one can join as a member (voting or not) or how their leadership is selected.

National Autism Association

Recently ran into controversy over a fundraiser for their stance on vaccines. Supporter of Andrew Wakefield. They state on their website:

The National Autism Association believes:
Vaccinations can trigger or exacerbate autism in some, if not many, children, especially those who are genetically predisposed to immune, autoimmune or inflammatory conditions.

One can become a dues-paying member of the NAA. Their most recent IRS form 990 shows that they took in $4,775 in dues. That would be fewer than 150 dues paying members at their $35 tier.

I can not see how leadership is selected; whether the membership is allowed to vote in open elections.

SafeMinds

One of the first organizations formed around the idea that vaccines cause autism. In specific, SafeMinds is focused on thimerosal in vaccines. The leadership has many of the same people over the past decade and I can’t see where one could join and whether if members are allowed, if they are allowed to vote for leadership.

Talk About Curing Autism

Another org that is strongly behind the vaccine-autism link.
(and here). It’s unclear if or how one would become a voting member. The leadership has been largely unchanged since founding.

The Thinking Mom’s Revolution

While I’m very fond of blogs, I don’t see them as organizations. Again, where does one join or vote for leadership? How does this blog count membership? Facebook likes?

I believe every one of the above groups considers Andrew Wakefield to be a hero, ignoring his proved ethical lapses (he was stripped of his medical license and the fact that his ideas on vaccines and autism have been shown to be wrong (e.g. Lack of Association between Measles Virus Vaccine and Autism with Enteropathy: A Case-Control Study to select one of many)

I am a public member to the IACC, which was set up by the reathorization in 2011. All views above (and anywhere) are my own. While there are certainly things I would hope could be done differently in the way the U.S. manages autism research, handing control over to a few small groups so they can push a failed agenda on vaccines is not the direction we should go. Scuttling the reauthorization because support is not going into further research on this failed idea is also not the direction we need to take. Not at all.

It’s very telling that these groups for the most part hide or downplay their position on vaccines. The NAA, for example, recently ran into controversy about their stance and lost a fundraising opportunity with the national restaurant chain Chilis. The NAA leadership paid lip service to effect that the statements on their website are old views, but those statements remain. They know this position is a liability in public. But rather than accept that the view is a liability for good reason, they chose to downplay their views.

I don’t know if many in the legislature are giving them a serious listen, but I hope not. These groups do not represent the autism communities. They certainly are not showing an effective leadership, working to scuttle a law and lose hundreds of millions of dollars in funding if their own failed ideas are not supported.


By Matt Carey

ASAN Letter Expressing Concern re: House Subcommittee Hearing on Autism

18 May

A hearing has been scheduled for next week with the Committee on Oversight and Government Reform for it’s Subcommittee on Government Operations.

The hearing, Examining the Federal Response to Autism Spectrum Disorders, is scheduled for Tuesday, May 20, 2014.

The Autistic Self Advocacy Network (ASAN) has issued a letter expressing concern over the apparent lack of autistic input to the hearing. That letter is quoted below.

ASAN Letter Expressing Concern re: House Subcommittee Hearing on Autism

May 17, 2014
Dear Chairman Mica and Ranking Member Connolly:

On behalf of the Autistic Self Advocacy Network, the nation’s leading advocacy organization run by and for autistic people, I write to express concern about the upcoming May 20th, 2014 Subcommittee on Government Operations hearing entitled “Examining the Federal Response to Autism Spectrum Disorders.” To our knowledge, no autistic witnesses or representatives from organizations run by Autistic people have been invited to testify. ASAN is profoundly concerned by the apparent absence of representatives from organizations run by autistic people and urges that the hearing not go forward without representation by those most directly impacted by federal autism policy.

Autistic individuals are uniquely suited to testify about which federal activities are most needed in order to improve our own lives. Accordingly, when the House Committee on Oversight and Government Reform proposed a hearing on autism in November 2012, ASAN and other disability rights organizations voiced strong opposition to the planned absence of witnesses from organizations run by autistic people at that hearing and was pleased when the organizers of that hearing responded by inviting two autistic witnesses representing organizations run by autistic people to testify. The presence of autistic voices at the November 2012 hearing helped to enrich the conversation about the federal government’s response to autism.

We are disappointed by the prospect that, to our knowledge, the Committee has not invited Autistic witnesses from organizations run by autistic people to the upcoming hearing. It would truly be unfortunate if the progress Congress made in 2012 were reversed in 2014. ASAN appreciates the Subcommittee’s interest in federal autism policy and urges it to ensure the inclusion of witnesses from organizations run by and for autistic adults in its witness list. We stand ready to assist the Subcommittee in its efforts. If we can be of any assistance, please feel free to contact us via ASAN’s Director of Public Policy, Samantha Crane, at scrane@autisticadvocacy.org.

Sincerely,

Ari Ne’eman
President
Autistic Self Advocacy Network

cc: Chairman Darrell E. Issa
cc: Ranking Member Elijah Cummings

ASAN Statement Opposing House CAA Re-authorization Legislation H.R. 4631

15 May

The Autistic Self Advocacy Network (ASAN) has issued a statement on the re-authorization of the Combating Autism Act:

ASAN Statement Opposing House CAA Re-authorization Legislation H.R. 4631

The Autistic Self Advocacy Network is deeply concerned by the recently introduced Combating Autism Re-authorization Act of 2014 (H.R. 4631). H.R. 4631 fails to address many of the longstanding problems in the CAA, including the lack of funding and attention to research on services and the needs of adults, failure to include adequate self-advocate representation on the Interagency Autism Coordinating Committee (IACC) and the use of language offensive to and stigmatizing of Autistic Americans. Currently, only a small fraction of federal research funding focuses on effective delivery of services or on the needs of autistic adults, both of which are issues of pressing concern to autistic people and their families. Of NIH’s $217 million investment in autism research, only 2.4% has gone towards improving services and only 1.5% toward research on the needs of adults.

H.R. 4631 would exacerbate these problems by extending the existing structure of CAA to 2019. In addition, the legislation would create four IACC members appointed by Congress, risking the further politicization of federal autism policy. The addition of four IACC membership positions to be awarded by politicians is particularly troubling in light of H.R. 4631’s continued neglect of a critical group that is currently dramatically underrepresented on the IACC: autistic people themselves. The IACC is only currently required to have one of its members be an individual with an autism spectrum diagnosis, a status quo that H.R. 4631 would perpetrate. Finally, CAA’s use of the language of “combating autism” shows a profound disrespect and lack of concern for the preferences of autistic people and our families who find such language offensive and hurtful. H.R. 4631 maintains that language.

Last month, ASAN was joined by eighteen other disability rights organizations calling for reforms to CAA to address these problems. Regrettably, H.R. 4631 has undertaken no such changes, preferring to deepen commitment in a status quo that actively works against the interests of autistic people and our families. Support for legislation that perpetrates dangerous and hurtful trends in the lives of Autistic Americans is incompatible with friendship with the self-advocate community. Until such time as these issues are addressed, ASAN strongly urges opposition to H.R. 4631.

What Can I Do?

1) Contact Your Member of Congress and Urge Them To Oppose H.R. 4631. You can reach your Representative by calling the Capitol Switchboard at (202) 224-3121 or by using this phone tool from the Arc of Maryland.

2) Tweet to your Representative why you oppose H.R. 4631 – use the hashtag #StopCombatingMe to help build momentum for our campaign.

3) If you belong to an advocacy organization, contact ASAN about signing on to our joint letter opposing H.R. 4631 by e-mailing Samantha Crane, ASAN’s Director of Public Policy, at scrane@autisticadvocacy.org

Follow

Get every new post delivered to your Inbox.

Join 1,034 other followers