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Poul Thorsen indicted

14 Apr

Poul Thorsen, a Danish scientist who worked on many subjects including autism prevalence, was indicted in the United States today, the Atlanta Business Chronical reports. The article, Dane indicted for defrauding CDC, notes:

A Danish man was indicted Wednesday on charges of wire fraud and money laundering for allegedly concocting a scheme to steal more than $1 million in autism research money from the Atlanta-based Centers for Disease Control and Prevention.

Poul Thorsen started his association with the CDC as a visiting researcher. Later he moved to Denmark and Aarhus University.

According to the news article, Mr. Thorsen was using his position to create fraudulent invoices, and got his university to pay funds into his personal accounts in the US.

Mr. Thorsen worked on many projects. Most pertinent to this blog are his group’s efforts on autism epidemiology. These include works on MMR vaccines and thimerosal (e.g. A population-based study of measles, mumps, and rubella vaccination and autism and Thimerosal and the occurrence of autism: negative ecological evidence from Danish population-based data )

No charge has been made about the quality of these research projects or the conclusions drawn. However vaccine-causation advocates have been promoting the Thorsen case as part of their efforts.

Make no mistake: if guilty Poul Thorsen has committed very serious crimes. As a taxpayer, of course I am upset that this man might have stolen taxpayer money. As an autism parent, I can say without reservation that if found guilty Mr. Thorsen should be sentenced to the maximum sentence. The damage to the reputation of the research community which has sought to answer the questions of vaccine causation. A million dollars is a lot of money, but it is small change compared to the potential damage that might be caused .

Reassessing the role of mitochondrial DNA mutations in autism spectrum disorder.

12 Apr

Autism and mitochondrial medicine have become a very hot topic in recent years. What the connections are between autism and mitochondrial disorders has yet to be clarified. Mitochondria are little structures within cells that produce much of the energy required. Mitochondria have their own DNA (mtDNA) in addition to the nuclear DNA (nDNA) of the cell. nDNA is what most people think of when we hear “genes” or DNA. Given the focus on mitochondrial dysfunction and autism, it is natural to consider the question: are there mutations in the mtDNA which increase the risk of autism?

A new paper takes a look at the question. They studied 148 patients with ASD and found, well, no support for a link to mtDNA mutations. Here is the abstract:

BMC Med Genet. 2011 Apr 6;12(1):50. [Epub ahead of print]
Reassessing the role of mitochondrial DNA mutations in autism spectrum disorder.
Alvarez-Iglesias V, Mosquera-Miguel A, Cusco I, Carracedo A, Perez-Jurado LA, Salas A.
Abstract
ABSTRACT:
BACKGROUND: There is increasing evidence that impairment of mitochondrial energy metabolism plays an important role in the pathophysiology of autism spectrum disorders (ASD; OMIM number: 209850). A significant proportion of ASD cases display biochemical alterations suggestive of mitochondrial dysfunction and several studies have reported that mutations in the mitochondrial DNA (mtDNA) molecule could be involved in the disease phenotype.

METHODS: We analysed a cohort of 148 patients with idiopathic ASD for a number of mutations proposed in the literature as pathogenic in ASD. We also carried out a case control association study for the most common European haplogroups (hgs) and their diagnostic single nucleotide polymorphisms (SNPs) by comparing cases with 753 healthy and ethnically matched controls.

RESULTS: We did not find statistical support for an association between mtDNA mutations or polymorphisms and ASD.

CONCLUSIONS: Our results are compatible with the idea that mtDNA mutations are not a relevant cause of ASD and the frequent observation of concomitant mitochondrial dysfunction and ASD could be due to nuclear factors influencing mitochondrion functions or to a more complex interplay between the nucleus and the mitochondrion/mtDNA.

PMID: 21470425 [PubMed – as supplied by publisher]Free Article

This is consistent with previous studies, as noted in a recent review article which was itself summarized at The Thinking Person’s Guide to Autism by Emily Willingham as Mitochondrial Disease and Autism: Linked?

Ms. Willingham noted there:

Thus, tracking down mitochondrial dysfunction in the context of ASD to a specific mutation has remained an elusive goal. Two scenarios are likely for this lack of mutational findings: (1) there are mutations, but we just haven’t found them yet; or (2) the environment is largely responsible for any mitochondrial dysfunction that abnormal marker levels might indicate.

This paper is available as a free manuscript online. Here is the

Although it is widely accepted that some forms of ASD appear concomitantly with the impairment of mitochondrial energy metabolism, there are reasons to believe that the cause of these mitochondrial disorders does not systematically rest on mutations or variants in the mtDNA molecule. Pathogenic mtDNA mutations have been reported in ASD patients, but this seems to be the exception rather than the rule. It is more likely that the real causes of mitochondrial deficiencies in some ASD cases are due to the intervention of several nuclear factors acting alone (additively or epistatically) or through a complex interplay with mtDNA variants. For the time being, while the cause for mitochondrion dysfunction in ASD remains unclear, there is no reason to indicate systematic screening for mtDNA mutations in ASD patients unless a mitochondrion disorder is suggested by a clear phenotype.

What is also interesting to me is the table of characteristics of the study subjects. In particular, there is a big difference in the percentage with epilepsy and dimorphism between adults and children:

Mitochondrial dysfunction is listed as mild and somewhat infrequent (about 10%). Not the very high prevalences of mitochondrial dysfunction that some have suggested are present in autitics. This does beg the question: should this genetic study be performed on those with some measure of mitochondrial dysfunction?

This doesn’t mean that mitochondrial dysfunction isn’t an important area for autism research, or that a genetic study such as this shouldn’t be done on a larger group with some measure of mitochondrial dysfunction.

Of course it would be great to hear that there is something definitive in this study. As in, “this is it!” rather than “this probably isn’t it”. Mitochondrial DNA mutations “probably isn’t it” when it comes to the etiology of ASD in most people.

Effectiveness of virtual reality using Wii gaming technology in children with Down syndrome

11 Apr

I’ve read a lot about the benefits of the iPad over the past year. And, yes, it is a very good thing to add to the arsenal of tools to help disabled people. But the iPad is not the only new technology gadget on the market, and this was made clear in an article: Effectiveness of virtual reality using Wii gaming technology in children with Down syndrome.

Yep. The Wii. Here is the abstract:

Effectiveness of virtual reality using Wii gaming technology in children with Down syndrome.

Wuang YP, Chiang CS, Su CY, Wang CC.

Department of Occupational Therapy, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 807, Taiwan. yeepwu@cc.kmu.edu.tw
Abstract

This quasi-experimental study compared the effect of standard occupational therapy (SOT) and virtual reality using Wii gaming technology (VRWii) on children with Down syndrome (DS). Children (n = 105) were randomly assigned to intervention with either SOT or VRWii, while another 50 served as controls. All children were assessed with measures of sensorimotor functions. At post-intervention, the treatment groups significantly outperformed the control group on all measures. Participants in the VRWii group had a greater pre-post change on motor proficiency, visual-integrative abilities, and sensory integrative functioning. Virtual reality using Wii gaming technology demonstrated benefit in improving sensorimotor functions among children with DS. It could be used as adjuvant therapy to other proven successful rehabilitative interventions in treating children with DS.

Here is a big section of the discussion section of the paper. Basically, Standard Occupational Therapy (SOT) helps Down Syndrome (DS) kids do better on fine and gross motor skills. Using Virtual Reality Wii seems to help even more. Gotta love that.

Of the two intervention groups, children who received VRWii therapy demonstrated the largest increase in post-intervention scores on the BOT-2 gross motor subtests. Significant improvement in gross motor function may be accounted for by the accumulated effects from a series of training steps that are structured, progressive, goal-directed, and interrelated. For instance, once the child initially learned to maintain equilibrium on VRWii Sports items, more challenging dynamic tasks such as jumping, striking and catching balls were introduced. VRWii could allow the child to interact with a computer-simulated environment and receive near real-time augmented feedback on performance. After mastering the VRWii tasks, the child was better able to use body feedback to understand the movement outcomes (feedback), anticipate upcoming events (feedforward), and plan alternative strategies (Brooks, 1986). Simultaneously, the child was encouraged to rely more on internal feedback and self-evaluation of performance than external feedback from others and environment. By adjusting the difficult level of Wii Sport items, more mature patterns of motor control emerged from better use of feedback and feedforward mechanisms.

The VRWii group achieved the greatest progress primarily in the BOT-2 fine motor subtests as well. A probable explanation is that success with skilled fine motor tasks relies upon sophisticated motor control and higher-level motor planning. The nature of VRWii therapy promotes an optimal sensory intake by allowing the child to actively explore and organize diverse sensory inputs. An overall improved organization of sensory input may subsequently enhance motor planning and sequencing ability, thereby leading to the improvement in fine motor skills (Humphries, Wright, Snider, & McDougall, 1992). In addition, the improvement in hand function also depended on the child’s ability to modify the patterns of grasping Wii handle according to the different somatosensory input from diverse VRWii Sport items. An essential component of all extremities movements experienced in VRWii Sports is proactive visual and somatosensory control ([Augurelle et al., 2003], Jeannerod, 1986 M. Jeannerod, The formation of finger grip during prehension: A cortically mediated visuomotor pattern, Behavior and Brain Research 19 (1986), pp. 99–116. Abstract | PDF (1331 K) | View Record in Scopus | Cited By in Scopus (130)[Jeannerod, 1986] and [Jeannerod, 1990]), which is responsible for the correct execution of limb movement and the coordination between limbs and vision ([Johansson, 1996] and [Whitney and Wrisley, 2004]). Therefore, tasks involved with visual motor integration of VMI and BOT-2 were also improved by VRWii.

Unexpectedly, the VRWii group alone demonstrated larger increase in all TSIF subtest scores post intervention than SOT that included sensory integration therapy. This result offers direct evidence that children with DS are able to benefit from VRWii therapy to optimize the integrated processing of sensory cues and motor responses. VRWii itself could provide constant opportunities for children to integrate visual, vestibular, and proprioceptive inputs. In particular, significant gains in emotion and behavior subtest of the TSIF after VRWii intervention implies that the playfulness inherent in the VRWii items was able to tap into the children’s inner drive to engage with VRWii therapy. By actively participating in the goal-directed and enjoyable activities, the therapeutic effects could be maximized ([Larin, 2000] and [Parham and Mailloux, 2010]), and the psychosocial needs of children were fulfilled as well (Tye & Tye, 1992). The principle of Wii by using self-initiation, meaningful, and challenging activities in increasing neural plasticity coincided with the principles of sensory integration theory proposed by Ayres ([Ayres, 1972] and [Jacobs and Schenider, 2001]).

Researchers track down autism rates across the globe

8 Apr

The Simons Foundation blog, SFARI, has always had a good quality of articles. Lately it appears to me that the frequency of articles has increased. One recent article hits a subject that has been a focus of mine for some time: prevalence estimates and how they vary by culture and geography. In Researchers track down autism rates across the globe Virginia Hughes talks to a number of researchers working on expanding autism prevalence studies to more countries. Outside of the US and the UK, autism prevalence studies are somewhat rare. Until fairly recently, prevalence estimates outside of the US and Europe were basically nonexistent.

Ms. Hughes starts with this introduction:

In urban areas of South Korea, some families of children with developmental delays will go to great lengths to avoid a diagnosis of chapae, or autism. They think of it as a genetic mark of shame on the entire family, and a major obstacle to all of their children’s chances of finding suitable spouses.

The stigma is so intense that many Korean clinicians intentionally misdiagnose these children with aechak changae, or reactive detachment disorder — social withdrawal that is caused by extreme parental abuse or neglect.

This won’t come as a surprise for those who have read Roy Richard Grinker’s Unstrange Minds, where Prof. Grinker explores how autism is viewed in various parts of the world, including South Korea.

Prof. Grinker is interviewed, as is his collaborator Dr. Young Shin Kim, and Dr. Eric Fombonne.

Autism prevelance work has been performed or is ongoing in Mexico, South Korea, Brazil, India, South Africa and Oman. Since autism isn’t diagnosed through a biological test, variations in culture can have a significant impact on the test methods.

Ms. Hughes notes:

Language and culture may also affect the way this research is carried out. For instance, the Korean language uses an extensive array of suffixes that denote the relationship between the speaker and the subject. South Korean children with autism have trouble using these social markers, but the Western-based standard tests of autism, such as the Autism Diagnostic Observation Schedule (ADOS), don’t test for this.

Similarly, Grinker points out, healthy children from non-Western cultures may display a trait that ADOS counts as a symptom of autism. In South Korea, for example, making eye contact with an adult is not socially appropriate.

“This is why it’s pretty useful to have [anthropologists] who can translate diagnostic instruments that were designed in one culture and used in another,” Grinker says.

Rather than cut and paste the entire article I will point you back to SFARI for the full piece. It is well worth reading.

IAN Network Launches Critical Survey on Autism & Wandering

6 Apr

I received the following message from the Autism Science Foundation. The message discusses the survey to collect data on wandering by autistics. To participate, you need to register at the IAN Project website.

Today, the Interactive Autism Network (IAN) with support from leading autism advocacy groups including the Autism Science Foundation, launched the first major survey to study the experience of wandering and elopement, or escaping, among individuals with autism spectrum disorders (ASD). The tendency of individuals with ASD to wander or “bolt” puts them at risk of trauma, injury or even death, yet information on this critical safety issue is lacking.

Since 2007, the IAN Project, www.ianproject.org, has connected thousands of individuals on the autism spectrum and their families with researchers nationwide to accelerate the pace of autism research through an innovative online initiative housed at the Kennedy Krieger Institute in Baltimore, Maryland. With more than 36,000 participants today, the IAN Project has the largest pool of autism data in the world.

“Although similar behavior has been studied in Alzheimer’s disease and autism advocates identify elopement as a top priority, virtually no research has been conducted on this phenomenon in ASD,” said Dr. Paul Law, Director of the IAN Project at the Kennedy Krieger Institute. “The new survey will provide vital information to families, advocates and policy makers alike as they work to keep individuals with ASD safe.”

The survey will help researchers begin to answer important questions:

* How often do individuals with ASD attempt to elope? How often do they succeed? Under what circumstances?
* Which individuals with ASD are most at risk? At what age?
* What burden do efforts to thwart elopement behavior place on caregivers?
* What can be done to protect individuals with ASD and support their families?

To understand elopement and wandering behavior in ASD, researchers need information both from families of individuals who do and do not wander and elope. In order to determine who is at risk, all families in the U.S. autism community are encouraged to participate in the survey, whether or not their loved one engages in these behaviors. Survey participants must be enrolled in the IAN Project (to register, visit www.ianresearch.org) and be the parent or guardian of a child or dependent adult with ASD.

Due to the urgent need for this information by the autism community, preliminary data will be made available on April 20, 2011, provided the necessary sample size is reached for the research survey.

This survey is funded by the Autism Research Institute, Autism Science Foundation, Autism Speaks and Global Autism Collaboration. The IAN Project is also supported by the Simons Foundation and the National Institutes of Health.

Social-sexual education in adolescents with behavioral neurogenetic syndromes

30 Mar

A recent paper abstract I read brought up a very important topic which I don’t see discussed much: sex education for adolescents with developmental disabilities. I don’t know how good the paper itself is, but I agree with the conclusion: “Social and sexual education programs are of the utmost importance for adolescents with neurogenetic developmental disabilities. ” On one level I don’t want to think about sex and my kid. But I also have run into a belief that sex isn’t a topic to consider for people with developmental disability and autistics in particular. Perhaps I am naive, but I don’t see this as a good approach. I think sexuality is too important a topic to leave unaddressed. The discussion is going on. Just rarely in the parent-oriented online world.

Isr J Psychiatry Relat Sci. 2010;47(2):118-24.
Social-sexual education in adolescents with behavioral neurogenetic syndromes.

Plaks M, Argaman R, Stawski M, Qwiat T, Polak D, Gothelf D.
The Behavioral Neurogenetics Center, Feinberg Department of Child Psychiatry, Schneider Children’s Medical Center of Israel, Petah Tikwa, Israel.

Abstract
BACKGROUND: Adolescents with developmental disabilities have unmet needs in their sexual and social knowledge and skills. We conducted a sexual social group intervention in adolescents with neurogenetic syndromes, mainly with Williams and velocardiofacial syndromes and their parents.
METHOD: Ten adolescents with neurogenetic syndromes and 14 parents participated in a Social Sexual Group Education Program. The program was delivered in 10 biweekly sessions to the adolescents and their parents separately.
RESULTS: The focus of psychoeducation in both groups was the adolescents’ self-identification, acceptance of the developmental disability, independence, establishment of friendship and intimate relationship, sexual knowledge and sexual development, and safety skills. Change in independent activities of adolescents and in their concept of “Friend” was measured.
CONCLUSIONS: Social and sexual education programs are of the utmost importance for adolescents with neurogenetic developmental disabilities. These programs should start already before adolescence and follow the children into young adulthood.

Telescoping of caregiver report on the Autism Diagnostic Interview – Revised.

29 Mar

One issue that comes up a lot is the reliability of parents’ memories about the development of their children. This can be especially hard the more time that passes and we look back, potentially “telescoping” events. In a recent study, researchers from the University of Michigan, including Catherine Lord, look at telescoping of reports. What they found what that as time went on, parent reports language delays changed. As time went on, parents reported language delays where delays weren’t reported when the children were younger. Interestingly to me, age of “symptom onset” increased with time. I find this interesting because I have read a few discussions online where as time has gone on, parents have reported “symptom onset” occurred at earlier ages. Reports of age of first concerns of delays, daytime bladder control and independent walking did not vary with time.

Here is the abstract.

Telescoping of caregiver report on the Autism Diagnostic Interview – Revised.

Abstract

Background: Delays in development are a fundamental feature in diagnosing autism spectrum disorders (ASD). Age of language acquisition, usually obtained through retrospective caregiver report, is currently used to distinguish between categories within ASD. Research has shown that caregivers often report children as having acquired developmental milestones earlier or later than they were actually achieved. The current study examines the extent to which this phenomenon, referred to as ‘telescoping,’ impacts retrospective reports provided by caregivers of children with ASD.

Methods: Participants were 127 caregivers of children referred for possible ASD or non-spectrum developmental delay. Caregivers were interviewed when children were 2, 3, 5, and 9 years of age. Caregiver-reported ages of first concern, language and non-diagnostic developmental milestones and interviewer-estimated age of onset were compared over time using linear models.

Results: Significant telescoping of language milestones resulted in more children meeting language delay criteria as they grew older, in spite of original reports that their language was not delayed. There was little evidence of consistent telescoping of caregiver-reported ages of first concern, daytime bladder control, and independent walking. With time, the interviewers’ judged ages of symptom onset increased, but remained prior to age three.

Conclusions: Telescoping of caregiver-reported ages of language acquisition has implications for both clinical diagnosis and genetic studies using these milestones to increase homogeneity of samples. Results support proposals to remove specific age-based criteria in the diagnosis of ASD. Telescoping should be considered when working with any clinical population in which retrospectively recalled events are used in diagnosis.

Yes, we’d like to think we are all excellent at recalling details about our kid’s development. But sometimes memory is not the best gauge. Sometimes data is best.

Sweden to check birth blood samples of autistic Somalis

29 Mar

Swedish researchers explore Somali-autism link discusses a study to use blood samples from samples taken at birth:

The researchers at the Autism centre for small children in Stockholm want to see if the samples contained in the so-called PKU register, which is used on newborns to detect a slew of illnesses, can explain the differences in levels of autism between children of Somali and children of Swedish origin.

“We want to look at the vitamin D levels at a very early stage in children who are later diagnosed with autism,” Elisabeth Fernell at the Autism centre for small children told the Dagens Nyheter (DN) daily.

The story linked to above has some weaknesses, but it is interesting that the study is being undertaken. People are looking at the question. This group in Sweden. The CDC together with Autism Speaks in the US. The Minnesota Department of Public Health.

No association between early gastrointestinal problems and autistic-like traits in the general population

28 Mar

Gastrointesintal problems are a common topic of discussion and debate in the online autism communities. Much of the discussion involves causation: do GI problems cause autism? A recent study looks at a tangent of this argument. Considering the general population, do GI problems early in life predict autistic traits later in life? The methodology isn’t the strongest: they use parent reports of GI complaints and the self-report questionaire Autism Quotient. They also asked about whether the individuals were immunized with the MMR vaccine.

The results:

There was no statistically significant difference in AQ scores between those who had (n=133) and those who had not (n=671) experienced early gastrointestinal symptoms. (2) analyses revealed that the children with early gastrointestinal problems were no more likely to be represented in the upper quintile of scores on any of the AQ scales. The measles, mumps, and rubella vaccination was unrelated to gastrointestinal symptoms or AQ scores.

The abstract is quoted below:

No association between early gastrointestinal problems and autistic-like traits in the general population

Aim
The aim of this study was to determine whether gastrointestinal problems in early childhood relate to autistic-like traits in a general population sample.

Method
The parents of 804 children (442 females; 362 males) reported at 1-, 2-, 3-, and 5-year follow-ups whether their child had been taken to a hospital, general practitioner, or health clinic for any of five gastrointestinal symptoms: (1) constipation; (2) diarrhoea; (3) abdominal bloating, discomfort, or irritability; (4) gastro-oesophageal reflux or vomiting; and (5) feeding issues or food selectivity. Parents also reported whether their child had received the measles, mumps, and rubella vaccination. Autistic-like traits were measured when the children had reached early adulthood (mean age 19y 7mo; SD 0.63y) using a self-report questionnaire, the Autism Spectrum Quotient (AQ).

Results

There was no statistically significant difference in AQ scores between those who had (n=133) and those who had not (n=671) experienced early gastrointestinal symptoms. (2) analyses revealed that the children with early gastrointestinal problems were no more likely to be represented in the upper quintile of scores on any of the AQ scales. The measles, mumps, and rubella vaccination was unrelated to gastrointestinal symptoms or AQ scores.

Interpretation

Parent-reported gastrointestinal problems in early childhood are unrelated to self-reported autistic-like traits in the general population.

Detection of Plasma Autoantibodies to Brain Tissue in Young Children with and without Autism Spectrum Disorders

25 Mar

Researchers at the MIND Institute published studies in the past few years correlating antibodies to brain tissue and autism. The first study of this sort (that I recall) studied whether the mother had antibodies to fetal brain tissue: Autism: maternally derived antibodies specific for fetal brain proteins. Other studies have looked at autoantibodies within the plasma of the autistics themselves: Detection of autoantibodies to neural cells of the cerebellum in the plasma of subjects with autism spectrum disorders.

The idea is fairly simple. If the mother or the autistic has antibodies against brain tissue, this might lead to an increased risk of autism.

There are even patent applications in for use of these methods to For example, a 2011 patent application US20110038872A1: METHODS OF DIAGNOSING AND TREATING AUTISM:

Determining a risk of an offspring for developing an autism spectrum disorder comprises identifying in a biological sample from the mother of the offspring in the presence of maternal antibodies that bind to the biomarkers

This past week, another paper from the MIND group came out:

Detection of Plasma Autoantibodies to Brain Tissue in Young Children with and without Autism Spectrum Disorders

In this study they looked for autoantibodies and compared autistics and non-autistics. They found no differences between the groups in frequency of autoantibodies.

Abstract
Autism spectrum disorders (ASDs) are characterized by impaired language and social skills, often with restricted interests and stereotyped behaviors. A previous investigation of blood plasma from children with ASDs (mean age = 5½ years) demonstrated that 21% of samples contained autoantibodies that reacted intensely with GABAergic Golgi neurons of the cerebellum while no samples from non-sibling, typically developing children showed similar staining (Wills et al., 2009). In order to characterize the clinical features of children positive for these autoantibodies, we analyzed plasma samples from children enrolled in the Autism Phenome Project, a multidisciplinary project aimed at identifying subtypes of ASD. Plasma from male and female children (mean age = 3.2 years) was analyzed immunohistochemically for the presence of autoantibodies using histological sections of macaque monkey brain. Immunoreactivity to cerebellar Golgi neurons and other presumed interneurons was observed for some samples but there was no difference in the rate of occurrence of these autoantibodies between children with ASD and their typically developing peers. Staining of neurons, punctate profiles in the molecular layer of the dentate gyrus, and neuronal nuclei were also observed. Taken together, 42% of controls and subjects with ASD demonstrated immunoreactivity to some neural element. Interestingly, children whose plasma reacted to brain tissue had scores on the Child Behavior Checklist (CBCL) that indicated increased behavioral and emotional problems. Children whose plasma was immunoreactive with neuronal cell bodies scored higher on multiple CBCL scales. These studies indicate that additional research into the genesis and prevalence of brain-directed autoantibodies is warranted.

” Immunoreactivity to cerebellar Golgi neurons and other presumed interneurons was observed for some samples but there was no difference in the rate of occurrence of these autoantibodies between children with ASD and their typically developing peers.”

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