Santa Claus

24 Dec

When it comes to Christmas I admit to being very orthodox in my beliefs. In particular, I believe that Santa comes at night and leaves presents for us to discover in the morning. Children are meant to wake up at some unbelievable hour like 4am and, after much discussion amongst siblings, tiptoe into their parents’ room to poke the parents and ask these groggy adults if Santa has come yet. Then begins the struggle with parents hoping against hope that they will be able to put off the inevitable until at least six AM. After many exchanges of “I think I heard him” and “no he hasn’t been here yet” parents compromise on 5:30 and strong coffee.

Nothing beats the excitement of kids rushing to open presents. It is best if you live in a two story house so the kids can run down the stairs, making as much noise as possible.

I was shocked to learn late in life that some families actually exchange gifts on Christmas eve. Sure this lets the parents sleep on Christmas day, but when is Santa supposed to sneak into the house and leave presents.

Turkey is the proper Christmas dinner main course. Cranberry sauce can be either that dark red jello substance or have berries still in it. It is so bitter (at least when you are a kid) that it is just a decoration anyway. I do have a fondness for the canned jello like version, especially if it has the shape of the can still.

The proper pie is pumpkin. Turkeys should be large enough to provide sandwiches for days. The turkey is carved before sitting down to dinner. The best slice is the one mom lets you steal as she carves.

The main concern is presents. Presents need to be under the tree well in advance of Christmas so that kids can shake them and guess what is in them. Anticipation. That’s the key.

This is how a proper Christmas is done.

For me.

In my childhood.

Parts of this tradition I share now with my own family. Parts have been modified. New traditions have been added.

For those of you with different traditions or no traditions for Christmas, I wish you well, too.

I’m a Christmas person

23 Dec

As some holidays have past and more are soon to come, I have to out myself: I am a Christmas person.

I would put myself more in the Christmas Tree and Santa camp:

Rather than the baby Jesus and midnight mass camp:

Hanukkah recently came and went recently:

But even after Christmas we still have Kwanza to look forward to:

Some may call Kwanza a “made up” holiday. Guess what, all holidays are “made up”.

The Winter Solstice has been a reason to gather and celebrate probably since before all the other “major” holidays.

And, there are many who don’t celebrate at this time of year at all.

We don’t have to think alike. We don’t have to believe alike. We don’t have to celebrate alike. There is a certain beauty and value in that.

A Christmas message of woe from Generation Rescue and Jenny McCarthy

22 Dec

I just got the Generation Rescue end-of-year fundraiser email. Jenny McCarthy tells us about how there are only two types of autism parents:

Dear Fellow Warrior,

My mantra is Never Give Up. This year, we “never gave up” in spades!

This year I had the honor of giving the keynote address at the AutismOne conference. The largest gathering of families, physicians and researchers pursuing biomedical treatment. I talked about trains. First, there’s Train A

You do absolutely everything you can for your child, no matter what anyone tells you. Then, there’s Train B: Woe is me. We are Train A People. Which isn’t always easy, right? But it’s always, always worth it.

and it goes on.

If Jenny McCarthy wants to slam other parents as “giving up” and being “woe is me” types, I guess that’s her right. She’s certainly taken a lot of criticism.

Of course, if I want to respond to her, that is my right as well.

As I near Christmas, the last thing on my mind is “woe is me”. I do still feel like I will listen to the advice of others, when they are experts, in seeking help for my child. If an expert says something like, “you know, that industrial chelator has not been tested adequately for safety or efficacy…or at all…in humans”, I take that to heart. When an expert in toxicology says, “you know, autism doesn’t actually look like mercury poisoning at all”, I take that to heart. When I read online discussions where parents are reporting adverse reactions to so-called “biomedical” approaches to treating autism, I take that to heart as well.

Safety. That is where you and I part ways, Jenny. Safety. You, your organizations and the practitioners you promote want me to “do absolutely everything”, regardless of whether it has been proven safe or effective.

It’s easier to put me in a box and tell your followers I am sitting here saying “woe is me” than to address the question of safety. Perhaps 2011 will be the year you take on the very serious question of safety.

Have a merry Christmas, Jenny. I will.

Edit-to-add:

Here is Jenny McCarthy’s message set to video.

And, also to add–

I am not on Train-A, but the A-train…no “woe is me” on the A-train.

Mitochondrial Dysfunction in Autism

22 Dec

A recent paper from the MIND Institute, published in the Journal of the American Medical Association (JAMA) entitled Mitochondrial Dysfunction in Autism caused a bit of a stir. One which is far beyond what is supported by the paper’s conclusions or data, I will add.

The study is very small: 10 autistic children and 10 controls. The authors used a very nonstandard methodology. Perhaps the best summary of this study so far can be found on the Simons Foundation blog SFARI (Defects in mitochondria linked to autism). Deborah Rudacille discusses the methodology and brings in quotes from the study’s lead author (Cecilia Giulivi) as well as established experts in the field of mitochondrial disease and autism such as Jay Gargas.

Before I get too far ahead of myself, here is the abstract:

Context Impaired mitochondrial function may influence processes highly dependent on energy, such as neurodevelopment, and contribute to autism. No studies have evaluated mitochondrial dysfunction and mitochondrial DNA (mtDNA) abnormalities in a well-defined population of children with autism.

Objective To evaluate mitochondrial defects in children with autism.

Design, Setting, and Patients Observational study using data collected from patients aged 2 to 5 years who were a subset of children participating in the Childhood Autism Risk From Genes and Environment study in California, which is a population-based, case-control investigation with confirmed autism cases and age-matched, genetically unrelated, typically developing controls, that was launched in 2003 and is still ongoing. Mitochondrial dysfunction and mtDNA abnormalities were evaluated in lymphocytes from 10 children with autism and 10 controls.

Main Outcome Measures Oxidative phosphorylation capacity, mtDNA copy number and deletions, mitochondrial rate of hydrogen peroxide production, and plasma lactate and pyruvate.

Results The reduced nicotinamide adenine dinucleotide (NADH) oxidase activity (normalized to citrate synthase activity) in lymphocytic mitochondria from children with autism was significantly lower compared with controls (mean, 4.4 [95% confidence interval {CI}, 2.8-6.0] vs 12 [95% CI, 8-16], respectively; P = .001). The majority of children with autism (6 of 10) had complex I activity below control range values. Higher plasma pyruvate levels were found in children with autism compared with controls (0.23 mM [95% CI, 0.15-0.31 mM] vs 0.08 mM [95% CI, 0.04-0.12 mM], respectively; P = .02). Eight of 10 cases had higher pyruvate levels but only 2 cases had higher lactate levels compared with controls. These results were consistent with the lower pyruvate dehydrogenase activity observed in children with autism compared with controls (1.0 [95% CI, 0.6-1.4] nmol × [min × mg protein]?1 vs 2.3 [95% CI, 1.7-2.9] nmol × [min × mg protein]?1, respectively; P = .01). Children with autism had higher mitochondrial rates of hydrogen peroxide production compared with controls (0.34 [95% CI, 0.26-0.42] nmol × [min × mg of protein]?1 vs 0.16 [95% CI, 0.12-0.20] nmol × [min × mg protein]?1 by complex III; P = .02). Mitochondrial DNA overreplication was found in 5 cases (mean ratio of mtDNA to nuclear DNA: 239 [95% CI, 217-239] vs 179 [95% CI, 165-193] in controls; P = 10?4). Deletions at the segment of cytochrome b were observed in 2 cases (ratio of cytochrome b to ND1: 0.80 [95% CI, 0.68-0.92] vs 0.99 [95% CI, 0.93-1.05] for controls; P = .01).

Conclusion In this exploratory study, children with autism were more likely to have mitochondrial dysfunction, mtDNA overreplication, and mtDNA deletions than typically developing children.

As the abstract states, the MIND Institute study methodology involved: “Mitochondrial dysfunction and mtDNA abnormalities were evaluated in lymphocytes from 10 children with autism and 10 controls”. Lymphocytes (a type of white blood cell). Children were concecutively recruited and genetically unrelated. Mitochondrial function was tested first, and given the results seen, children were brought back for a second blood draw where mitochondrial DNA (mDNA) and nuclear DNA (nDNA) were examined.

As shown in the figure below, they found that the autistic children had different mitochondrial activity levels than their controls. Note that “low” activity is not referenced to any standardized norms, but to the 10 control children.

They also performed genetic testing. Table 3 from the paper is reproduced below:

They show that, by their methodology, 7 of their 10 autistic kids have some form of genetic signature for mitochondrial dysfunction. 2 of 10 of their controls meet their criteria as well.

The Simons blog quotes the study author, Prof. Giulivi on this choice:

“Lymphocytes do not rely as heavily on mitochondria as the brain does,” she says, “so if this is happening in cells that don’t use mitochondria as much, it’s likely to be happening in cells that rely more heavily on mitochondria, like neurons.”

They also quote Dr. Fernando Scaglia, of the Baylor Clinic:

However, the unconventional decision to use lymphocytes should have been validated, says Fernando Scaglia, associate professor of molecular and human genetics at Baylor College of Medicine in Houston. “I’m not saying that studies done in lymphocytes are useless,” says Scaglia, an expert in inherited metabolic disease. “But they should be validated in other tissue.”

and Prof. Gargas of the University of California at Irvine:

“Lymphocytes are fine to study chromosomal DNA, but they are a horrible source for studying mitochondrial DNA,” he says.

Cells have hundreds of mitochondria, each with multiple copies of the DNA. In people with mitochondrial disease, some cells have healthy DNA and others have the mutated copies, he notes. In a blood sample, defective lymphoctyes tend to get lost among rapidly proliferating healthy cells.

“The best source for studying mitochondria are post-mitotic cells such as muscle,” he says. “That way you are sampling the set of cells the child was born with.”

In the end, if we stick to the idea that this is a very preliminary report and relies on a new unproven methodology at that, we can consider the study as posing interesting questions. Is mitochondrial dysfunction more prevalent in autistics than the general population? Are there ways to test this in a faster, less intrusive manner than is often used? If we take this study in context, there may be some value. Unfortunately as Seth Mnookin has already pointed out, this study has already been used to promote ideas that are clearly outside of the study and conclusions. This is the unfortunate world of autism research: it is hard for people to push the boundaries and risk being wrong. Not because it may cause the researchers some embarrassment, but because there are a multitude of people waiting to misuse information and mislead.

Commentary on Mitochondrial Dysfunction in Autism

22 Dec

I recently wrote about the paper Mitochondrial Dysfunction in Autism by the MIND Institute. It is difficult to write about the topic of mitochondrial dysfunction and mitochondrial disorders and autism without discussing vaccines. Even the Simons Foundation blog mentioned vaccines in their treatment of the paper, even though the paper makes no comments about vaccines.

Why? Because the case of Hannah Poling and, especially, the way David Kirby presented it to the public has linked autism–mitochondrial dysfunction–vaccines into one neat package. With posts like “NEW STUDY – “Mitochondrial Autism” is Real; Vaccine Triggers Cannot Be Ruled Out” and “The Vaccine-Autism Story: Trust Your Government, or Be a Patriot and Get on Google”. In the latter post he wrote:

“Google “autism and mitochondria,” (96,900 hits) and then Google “mercury and mitochondria,” (169,000 hits) and draw your own, informed conclusions. “

It was very much in David Kirby’s style. Don’t come out and say something directly (like, “mercury is the cause of mitochondrial disease”) but lead the reader along with a series of, well, leading statements.

A more responsible approach would be that one needn’t trust the government nor seek advice on google. A more responsible approach for Mr. Kirby would be to suggest that perhaps, just perhaps, parents of autistic kids should seek out the advice of experts in mitochondrial medicine. Mr. Kirby clearly had an agenda, and it wasn’t the well being of autistics. He was promoting the idea that vaccines caused an autism epidemic.

Mr. Kirby thankfully appears to have moved on from focusing his attention on promoting the vaccine-autism hypotheses. And yet, there is obviously a hunger amongst his old readers for this discussion. This can be seen in Mark Hyman’s blog post at the Huffington Post, “Autism Research: Breakthrough Discovery on the Causes of Autism” which has nearly 1,900 comments. Where David Kirby was promoting himself and the interests of groups like SafeMinds and Generation Rescue, Dr. Hyman uses the MIND Institute paper to promote himself and his own business.

What is worse is the way he goes about doing this. Dr. Hyman is even less capable of covering his obvious mistakes than was David Kirby.

Dr. Hyman writes:

While we don’t have all the answers, and more research is needed to identify and validate the causes and treatment of autism, there are new signs of hope. A study just published in The Journal of the American Medical Association by researchers from the University of California, Davis called “Mitochondrial Dysfunction in Autism” (i) discovered a profound and serious biological underpinning of autism — an acquired loss of the ability to produce energy in the cells, damage to mitochondria (the energy factories in your cells), and an increase in oxidative stress (the same chemical reaction that causes cars to rust, apples to turn brown, fat to become rancid, and skin to wrinkle). These disturbances in energy metabolism were not due to genetic mutations, which is often seen in mitochondrial problems, but a condition the children studied acquired in utero or after birth.

The statement is amazing. Not in a good way. It is amazing that someone could write such an irresponsible paragraph and attribute it to a paper which clearly doesn’t make or support these claims.

The very title of Dr. Hyman’s post (Autism Research: Breakthrough Discovery on the Causes of Autism) is in error. The study makes no claims about the causes of autism. Dr. Hyman didn’t have to look any farther than the paper itself which clearly states as one of the limitations:

Sixth, inferences about a cause and effect association between mitochondrial dysfunction and typical autism cannot be made in a cross-sectional study.

Given this, we can also throw out Dr. Hyman’s wild claim that the study’s authors “discovered a profound and serious biological underpinning of autism”.

Since it is already clear that Dr. Hyman is using the paper to promote his own ideas, regardless of the facts in the paper, I won’t posit as to why he claims that the mitochondrial dysfunction is “acquired”, or that this is due to “damage” to mitochondria. The paper does not support either of these conclusions as fact.

He makes the claim that “These disturbances in energy metabolism were not due to genetic mutations, which is often seen in mitochondrial problems, but a condition the children studied acquired in utero or after birth.”

I am unsure how Dr. Hyman reached this conclusion. The paper notes differences in the mtDNA of many of the children studied. It does not provide evidence as to when or how these genetic differences arose.

Table 3 clearly shows the genetic measures the MIND Institute researchers used. Question the method as you may (or some experts have), there are differences in the mtDNA. The methodology doesn’t allow one to state if these difference were present at birth or not.

The MIND Institute hosts an interview with Prof. Giulivi
At about 3:30 into Prof. Giulivi’s interview, she states clearly that they can not conclude if the mitochondrial dysfunction they claim causes autism or is a result of it.

It is hard for me to decide if Dr. Hyman is more irresponsible than David Kirby or if it is the other way around. David Kirby was certainly doing some self promotion, but his impact was largely as a publicist for the autism-as-vaccine-injury groups like SafeMinds and Generation Rescue. Dr. Hyman is clearly focused on promoting his own services as a practitioner of alternative medicine.

The problem is that in the end, rather than being a leader in treatment, as Dr. Hyman presents himself, such irresponsible actions hinder advancement.

Special Needs Trusts

20 Dec

In the United States, adults with disabilities can receive support through social security. But, if you have over $2,000 in assets, you don’t qualify. This leaves parents of disabled children in a bit of a quandary: how do you provide for your children after you are gone? From Lawyer.com:

In order to qualify for the Social Security Administration’s Supplemental Security Income Benefits, (“SSI”), a disabled adult can’t hold more than $2,000 in assets, excluding a car and a home. SSI benefits, which average about $400 per month, must be spent on food, clothing and shelter expenses.

Eligibility for SSI makes a disabled person eligible for food stamps and Medicaid, which pays medical expenses, nursing home care and mental health services. Medicaid eligibility also makes a disabled person eligible for many local community services, as well.

As these benefits add greatly to a disabled person’s ability to care for him or herself, you wouldn’t want to give your disabled child property that would disqualify him or her from receiving these benefits.

One way to plan for the future is with a “special needs trust” also known as a “supplemental needs trust”. This is a trust fund to supply those needs beyond those which Social Security might provide. One doesn’t have to put money into the trust right away, but can leave money to the trust on death.

The whole process of wills, trusts, supplemental needs trusts and so on can be pretty daunting, both legally and financially. Getting a lawyer to set these up can cost a few thousand dollars. It can be money well spent, and it can be more money than you might be able to afford right now. One excellent source of do-it-yourself legal advice is Nolo press. Nolo has a book on supplemental needs trusts: Special Needs Trusts/Protect Your Child’s Financial Future. I haven’t read this one yet, but I have found other books by Nolo to be well worth the money (this one is under $30).

Intervention Targeting Development of Socially Synchronous Engagement in Toddlers with Autism Spectrum Disorder: A Randomized Controlled Trial

18 Dec

Randomized Control Trials (RCT) are rare in research into autism interventions. One notable example was the Preschool Autism Communication Trial (PACT) which was published earlier this year and is discussed on the autismbc/autism vancouver blog as Intervention Fails to Reduce Autism Symptom.

This past week another RCT was published. I have not had the time to read the study yet, so I can’t discuss the methodology. Since I am unlikely to get to this for some time, I am posting this in the hope that someone who has read and digested the paper will be able to discuss it here.

Below is the blog post/press release from the National Institutes of Mental Health (which was one of the funding agencies for this study).

Targeting the core social deficits of autism spectrum disorders (ASD) in early intervention programs yielded sustained improvements in social and communication skills even in very young children who have ASD, according to a study funded by the National Institute of Mental Health (NIMH), part of the National Institutes of Health. The study was published online December 8, 2010, in the Journal of Child Psychology and Psychiatry.

Although some research suggests that ASD may be reliably diagnosed earlier than the current average age of 3 years, few interventions have been tested in children younger than 3.

During the course of typical development, children learn to interact with others in socially meaningful ways. Measures of social communication include:

* Initiation of joint attention—spontaneously directing others’ attention to something of interest, such as by pointing or holding something up to show for social purposes rather than to ask for help
* Affect sharing—sharing emotions with others through facial expressions paired with eye contact
* Socially engaged imitation—imitating others’ actions while showing social connectedness through eye contact.

Deficits in such measures are hallmark symptoms of ASD and can severely limit a child’s ability to engage in and learn from interactions with others or from the world around them.

“This new report is encouraging, as the effects on social behavior appear to provide a scaffold for the development of skills beyond the research setting,” said NIMH Director Thomas R. Insel, M.D. “We need better early interventions for the core deficits of autism.”

Funded through the Studies to Advance Autism Research and Treatment (STAART) Network, Rebecca Landa, Ph.D., of Kennedy Krieger Institute, Baltimore, and colleagues randomly assigned 50 toddlers, ages 21-33 months old, who were diagnosed with ASD to one of two six-month interventions: Interpersonal Synchrony (IS) or Non-Interpersonal Synchrony (non-IS). Both interventions incorporated classroom-based activities led by a trained intervention provider, and a home-based component involving parents who received specialized education and in-home training.

The interventions were designed to encourage children to make frequent and intentional efforts to engage others in communication or play. The single difference between interventions was that the IS group received more opportunities for joint attention, affect sharing, and socially engaged imitation. The toddlers were assessed at the start and end of the intervention and again six months later.

Children in both groups made improvements in social, cognitive and language skills during the six-month intervention period. Children who received IS made greater and more rapid gains than those in the non-IS group. The researchers also noted that children in the IS group used their newly acquired abilities with different people, locations, and type of activity. This is noteworthy because children with ASD have particular difficulty doing so. They tend to use new skills mostly within familiar routines and situations.

At the six-month follow-up, children in the IS group showed slower improvements in social communication compared to when they were receiving the intervention, but did not lose skills gained during the intervention period. In contrast, children in the non-IS group showed reduced social communication skills at follow-up compared to their performance during the intervention period.

“This is the first randomized controlled trial to examine an intervention focused on core social deficits of ASD in toddlers, and the first to show gains in these deficits resulting from intervention,” said Landa. “Though preliminary, our findings provide promising evidence that such a supplementary curriculum can help improve social and communication skills in children younger than 3 who have ASD.”

The researchers received additional study funding from the Health Resources and Services Administration.
Reference

Landa RJ, Holman KC, O’Neill AH, Stuart EA. Intervention Targeting Development of Socially Synchronous Engagement in Toddlers with Autism Spectrum Disorder: A Randomized Controlled Trial. J Ch Psychol Psychiatry. 2010 Dec 8. [epub ahead of print]

Recent autism abstracts in Pubmed

17 Dec

Pubmed is an amazing resource. It is a Public Medical library of abstracts (and some articles) in the medical literature. I have a search set up so that I get emails with recent articles with the subject “autism”. I try to obtain some of the articles and discuss them here. This is not based on what I perceive to be the “best” or “most important” work, just what I want to explore. It has been difficult lately to go into depth in any articles and I find myself falling behind. For example, a couple of days ago the pubmed email had 29 abstracts in one day. Given that, here are a few recent abstracts that caught my eye:

Neonatally measured immunoglobulins and risk of autism.

Grether JK, Croen LA, Anderson MC, Nelson KB, Yolken RH.

California Department of Public Health, Richmond, California.
Abstract

Previous studies indicate that prenatal exposure to infections is a possible pathway through which autism spectrum disorders (ASD) could be initiated. We investigated whether immunoglobulin levels in archived specimens obtained from newborns subsequently diagnosed with ASD are different from levels in newborn specimens from controls. Children with ASD born in six California counties in 1994 were ascertained through records of the California Department of Developmental Services (DDS) and Kaiser Permanente; controls were randomly selected using birth certificates. Archived newborn blood specimens were obtained from the California Genetic Disease Screening Program (GDSP) for N = 213 cases and N = 265 controls and assayed to determine levels of total IgG, antigen-specific IgG to selected common pathogens, total IgM, total IgA, and C-reactive protein (CRP). We did not find measurable levels of total IgM or IgA in any neonate and measurable CRP was present in only a few. No antigen-specific IgG antibodies were elevated in cases compared to controls and total IgG levels were lower. In adjusted models, a 10-unit increase in total IgG yielded an OR = 0.72 (95% CI 0.56, 0.91); a significantly decreasing trend in risk of ASD was observed across increasing exposure quartiles of total IgG (P = 0.01). The finding of lower IgG in cases may indicate maternal immune dysfunction during gestation and/or impaired transplacental transfer of immunoglobulins. Further investigation of IgG levels in newborns and the mechanisms by which they might be associated with ASD are warranted.

This follows on some previous work on maternal antibodies and autism risk. In 2008, UC Davis published: Autism: maternally derived antibodies specific for fetal brain proteins and Johns Hopkins published: Antibodies against fetal brain in sera of mothers with autistic children. These studies looked at the blood sera from mothers of autistic children–sera taken long after the autistic child was born–and found that in some cases there were antibodies in the mothers’ sera against fetal brain proteins. The current study (Grether et al.) looked at blood spots of newborns–samples from the children rather than the mother. They did not find measurable levels of IgM or IgA in the infant’s blood spots. They also did not find c-reactive protein (a response to inflammation).

This study out of France looked at autistic children age 5 and again at age 8. They found that most children’s characteristics were stable, but some did show improvement (e.g. in speech level). What is interesting was the statement that the amount of intervention (hours) was not related to outcome.

Outcome of young children with autism: Does the amount of intervention influence developmental trajectories?

Darrou C, Pry R, Pernon E, Michelon C, Aussilloux C, Baghdadli A.

Montpellier I University, Montpellier III University, France.
Abstract

The study aims were to identify developmental trajectories of young children with autism and investigate their prognostic factors. The participants were 208 children, assessed first at the age of 5 years, followed longitudinally, and reassessed 3 years later. The children’s clinical characteristics and the interventions received were recorded. The results indicated two distinct outcome groups with more stability than change. When changes did occur, they pertained to symptom severity (which decreased) and speech level and adaptive behavior (which improved). A logistic regression analysis pointed out two main risk factors (symptom severity and speech level) and two main protection factors (communication skills and person-related cognition). Surprisingly, the amount of intervention (in terms of number of hours) was not related to outcome.

Given a recent discussion here on LeftBrainRightBrain on genetics, heritability, de-novo mutations and copy number variations (CNV’s), I found the following abstract interesting.

Copy number variation characteristics in subpopulations of patients with autism spectrum disorders.

Bremer A, Giacobini M, Eriksson M, Gustavsson P, Nordin V, Fernell E, Gillberg C, Nordgren A, Uppströmer A, Anderlid BM, Nordenskjöld M, Schoumans J.

Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Abstract

Autism spectrum disorders (ASDs) are a heterogeneous group of disorders with a complex genetic etiology. We used high-resolution whole genome array-based comparative genomic hybridization (array-CGH) to screen 223 ASD patients for gene dose alterations associated with susceptibility for autism. Clinically significant copy number variations (CNVs) were identified in 18 individuals (8%), of which 9 cases (4%) had de novo aberrations. In addition, 20 individuals (9%) were shown to have CNVs of unclear clinical relevance. Among these, 13 cases carried rare but inherited CNVs that may increase the risk for developing ASDs, while parental samples were unavailable in the remaining seven cases. Classification of all patients into different phenotypic and inheritance pattern groups indicated the presence of different CNV patterns in different patient groups. Clinically relevant CNVs were more common in syndromic cases compared to non-syndromic cases. Rare inherited CNVs were present in a higher proportion of ASD cases having first- or second-degree relatives with an ASD-related neuropsychiatric phenotype in comparison with cases without reported heredity (P?=?0.0096). We conclude that rare CNVs, encompassing potential candidate regions for ASDs, increase the susceptibility for the development of ASDs and related neuropsychiatric disorders giving us further insight into the complex genetics underlying ASDs. © 2010 Wiley-Liss, Inc.

I am always very interested in efforts to identify autistic adults. In the following study, from the Netherlands, the ADOS is explored for reliability in an group of “high functioning” autism.

Diagnosing Autism Spectrum Disorders in Adults: the Use of Autism Diagnostic Observation Schedule (ADOS) Module 4.

Bastiaansen JA, Meffert H, Hein S, Huizinga P, Ketelaars C, Pijnenborg M, Bartels A, Minderaa R, Keysers C, de Bildt A.

Social Brain Lab, Department of Neuroscience, University Medical Center, Groningen, Hanzeplein 1, 9700 RB, Groningen, the Netherlands

Abstract

Autism Diagnostic Observation Schedule (ADOS) module 4 was investigated in an independent sample of high-functioning adult males with an autism spectrum disorder (ASD) compared to three specific diagnostic groups: schizophrenia, psychopathy, and typical development. ADOS module 4 proves to be a reliable instrument with good predictive value. It can adequately discriminate ASD from psychopathy and typical development, but is less specific with respect to schizophrenia due to behavioral overlap between autistic and negative symptoms. However, these groups differ on some core items and explorative analyses indicate that a revision of the algorithm in line with Gotham et al. (J Autism Dev Disord 37: 613-627, 2007) could be beneficial for discriminating ASD from schizophrenia.

Lastly, here is an article which I believe may have already been discussed online previously. From PLoS One (which means the article is available free) Which Neurodevelopmental Disorders Get Researched and Why? I don’t think it will come as a surprise to many readers of LeftBrainRightBrain that autism research has seen a particularly large rise in the past decade.

Aim

There are substantial differences in the amount of research concerned with different disorders. This paper considers why.

Methods

Bibliographic searches were conducted to identify publications (1985–2009) concerned with 35 neurodevelopmental disorders: Developmental dyslexia, Developmental dyscalculia, Developmental coordination disorder, Speech sound disorder, Specific language impairment, Attention deficit hyperactivity disorder, Autistic spectrum disorder, Tourette syndrome, Intellectual disability, Angelman syndrome, Cerebral palsy, Cornelia de Lange syndrome, Cri du chat syndrome, Down syndrome, Duchenne muscular dystrophy, Fetal alcohol syndrome, Fragile X syndrome, Galactosaemia, Klinefelter syndrome, Lesch-Nyhan syndrome, Lowe syndrome, Marfan syndrome, Neurofibromatosis type 1, Noonan syndrome, Phenylketonuria, Prader-Willi syndrome, Rett syndrome, Rubinstein-Taybi syndrome, Trisomy 18, Tuberous sclerosis, Turner syndrome, Velocardiofacial syndrome, Williams syndrome, XXX and XYY. A publication index reflecting N publications relative to prevalence was derived.

Results

The publication index was higher for rare than common conditions. However, this was partly explained by the tendency for rare disorders to be more severe.

Interpretation

Although research activity is predictable from severity and prevalence, there are exceptions. Low rates of research, and relatively low levels of NIH funding, characterise conditions that are the domain of a single discipline with limited research resources. Growth in research is not explained by severity, and was exceptionally steep for autism and ADHD.

Professor Simon Baron Cohen endorses Neurodiversity

16 Dec

Neurodiversity, that much misunderstood, much maligned concept has been dragged through the mud for years by people determined to misunderstand it and misrepresent it. We all know who these people are.

However, it also has its supporters and people determined to understand it on either a social or personal level. One such person is Professor Simon Baron-Cohen.

In an interview with the Encyclopaedia Britannica blog Professor Baron-Cohen was asked:

Individuals with Asperger syndrome often use the term “neurotypical” to describe normal people, and in an effort to lessen the stigmatization associated with autism as a medical condition, the Asperger community has initiated the so-called neurodiversity movement. Can you briefly describe the neurodiversity movement and its implications on the diagnosis of autism spectrum conditions?

To which he replied:

The neurodiversity movement has been a very positive influence in reminding us that there is no single pathway in neurological development, but there are many ways to reach similar end-points.

…

Stigmatizing anyone, whether they have autism or any other characteristic, is wrong, since the point about these labels is not to pick out the person in order to make their lives worse, but to help others understand their special needs and qualities.

How nice to see a researcher who _gets_ it.

Residential Proximity to Freeways and Autism in the CHARGE study

16 Dec

The U.C. Davis MIND Institute has an ongoing study to explore autism risk factors due to both genetic and environmental influences: the CHARGE study. The CHARGE study website describes itself as:

CHARGE (Childhood Autism Risks from Genetics and the Environment) was launched in 2003 as a study of 1,000 to 2,000 children with differing patterns of development. The goal is to better understand the causes and contributing factors for autism or developmental delay. Three groups of children are being enrolled in the CHARGE study: children with autism, children with developmental delay who do not have autism and children from the general population. All of them are evaluated for a broad array of exposures and susceptibilities.

A paper from this study was just released. In it, they claim that maternal proximity to freeways might be a risk factor for autism:

Residential Proximity to Freeways and Autism in the CHARGE study.

Volk HE, Hertz-Picciotto I, Delwiche L, Lurmann F, McConnell R.

Abstract

Background: Little is known about environmental causes and contributing factors for autism. Basic science and epidemiological research suggest that oxidative stress and inflammation may play a role in disease development. Traffic-related air pollution, a common exposure with established effects on these pathways, contains substances found to have adverse prenatal effects. Objectives: To examine the association between autism and residence proximity, during pregnancy and near the time of delivery, to freeways and major roadways as a surrogate for air pollution exposure. Methods: Data were from 304 autism cases and 259 typically developing controls enrolled in the Childhood Autism Risks from Genetics and the Environment (CHARGE) Study. The mother’s address recorded on the birth certificate and trimester specific addresses derived from a residential history obtained by questionnaire were geo-coded and measures of distance to freeways and major roads were calculated using ArcGIS software. Logistic regression models compared residential proximity to freeways and major roads for autism cases and typically developing controls. Results: Adjusting for sociodemographic factors and maternal smoking, maternal residence at the time of delivery was more likely be near a freeway (?309 meters) for cases, as compared to controls (odds ratio (OR), 1.86, 95% confidence interval (CI) 1.04-3.45). Autism was also associated with residential proximity to a freeway during the third trimester (OR, 2.22, CI, 1.16-4.42). After adjustment for socio-economic and demographic characteristics, these associations were unchanged. Living near other major roads at birth was not associated with autism. Conclusions: Living near a freeway was associated with autism. Examination of associations with measured air pollutants is needed.

Note: Pubmed lists the affiliation as the University of Southern California. I don’t know if any of these authors are from USC, but I know that CHARGE and Dr. Hertz-Picciotto are with the U.C. Davis MIND Institute.

It is an interesting idea and it will be interesting to see if this result holds up in studies with larger groups.

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