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Prevalence and Correlates of Autism in a State Psychiatric Hospital

24 Aug

I’ve said it before: I really like David Mandell’s work. He and his team take on some very important and tough questions. I am very concerned about the lack of information on autistic adults. We don’t know an accurate prevalence. Without study ongoing into the needs of autistic adults, those of us with autistic children will face a

That’s why I like studies like this one: Prevalence and Correlates of Autism in a State Psychiatric Hospital.

This study estimated the ASD prevalence in a psychiatric hospital and evaluated the Social Responsiveness Scale (SRS) combined with other information for differential diagnosis. Chart review, SRS and clinical interviews were collected for 141 patients at one hospital. Diagnosis was determined at case conference. Receiver operating characteristic (ROC) curves were used to evaluate the SRS as a screening instrument. Chi-squared Automatic Interaction Detector (CHAID) analysis estimated the role of other variables, in combination with the SRS, in separating cases and non-cases. Ten percent of the sample had ASD. More than other patients, their onset was prior to 12 years of age, they had gait problems and intellectual disability, and were less likely to have a history of criminal involvement or substance abuse. Sensitivity (0.86) and specificity (0.60) of the SRS were maximized at a score of 84. Adding age of onset <12 years and cigarette use among those with SRS 80 increased specificity to 0.90 but dropped sensitivity to 0.79. Undiagnosed ASD may be common in psychiatric hospitals. The SRS, combined with other information, may discriminate well between ASD and other disorders.

For reference:

Sensitivity relates to the test’s ability to identify positive results.
Specificity relates to the ability of the test to identify negative results.

Identifying autistic adults is not easy. Prevalence studies are far more difficult than when working with students. But Prof. Mandell is out there, trying to find autistic adults. In this case, he found that in a given psychiatric hospital, about 10% of the patients were autistic. He is calibrating instruments (the SRS together with correlates like smoking, age-of-onset, ID) to provide for a fairly direct screening tool.

This is one type of work that needs to be done. I’m glad that Prof. Mandell’s group is out there doing it, but I hope that more groups pick this up in the future.

Underimmunization in Ohio’s Amish: Parental Fears Are a Greater Obstacle Than Access to Care

29 Jun

With apologies for opening the subject of the Amish and autism once again, a recent paper in the journal Pediatrics explores vaccination and the Amish: Underimmunization in Ohio’s Amish: Parental Fears Are a Greater Obstacle Than Access to Care. Seth Mnookin has already discussed this at The Panic Virus at PLoS blogs in Anecdotal Amish-don’t-vaccinate claims disproved by fact-based study.

What is worrisome here is the fact that the nderimmunization amongst the Amish is resulting from parental fears. In a very different study from 2001, Haemophilus influenzae Type b Disease Among Amish Children in Pennsylvania: Reasons for Persistent Disease, most Amish parents who chose to not vaccinate were citing availability and convenience rather than fear as the reason.

To repeat–in 10 years the reasons for non-vaccinating amongst the Amish have changed from convenience to fear. We can’t say exactly why, but it seems quite plausible that the focus on autism, vaccines and the Amish could have played a role.

Given that the “Amish Anomaly” notion seems destined to linger on, I have written up another summary of the history and the facts of the story.

Dan Olmsted, now the owner of the Age of Autism, was once an editor for UPI. It was during his UPI time that he took on the autism/vaccine question that has since dominated his professional life. Back in 2005 he ran a series of stories which investigated the proposed link between autism and vaccines and, in specific, mercury. It was right around the time that the David Kirby/Lyn Redwood book “Evidence of Harm, Mercury in Vaccines and the Autism Epidemic: A Medical Controversy.” was published. This was likely the high water mark for the public’s acceptance of the vaccines-causation idea.

One of the ideas that Mr. Olmsted explored was that of the Amish. He started with the belief that they don’t vaccinate and set out to investigate whether this correlated with a lower autism prevalence. The idea of the Amish being a largely unvaccinated population was set out years earlier. David Kirby describes in Evidence of Harm how Lyn Redwood of SafeMinds discussed this in a presentation she made to congress in the year 2000.

Mr. Olmsted described his investigation starting in a piece, The Age of Autism: Mercury and the Amish . There was plenty of data even then which Mr. Olmsted could have considered which went against his hypothesis. Since then even more data has mounted against the idea.

And, yet, it persists. Often the “Amish don’t vaccinate and they don’t have autism” story pops up in internet discussions following news stories. Books have incorporated the idea. Of course it ends up in alternative medicine books on autism such as Kenneth Bock’s “Healing the New Childhood Epidemics: Autism, ADHD, Asthma, and Allergies”. The idea can be found in other boos as well, including “Timeless Secrets of Health and Rejuvenation” (2007) and “Cry for Health: Health: the Casualty of Modern Times” (2010). Again, this is a reason to revisit the debunking of this myth. The myth lives on, even in the face of facts.

In his 2005 UPI article, Mr. Olmsted started out with the assumption that the Amish don’t vaccinate. He set out to see if he could find autistics amongst the Amish, but didn’t look into the vaccination question with any depth:

So I turned to the 22,000 Amish in Lancaster County, Pa. I didn’t expect to find many, if any, vaccinated Amish: they have a religious exemption from the otherwise mandatory U.S. vaccination schedule.

As is well known now, the Amish do not have a religious exemption from the vaccine schedule. They do not have a religious prohibition against vaccination.

This was something Mr. Olmsted could easily have confirmed at the time. He might have checked the 1993 book Amish Society by John Andrew Hostetler (1993), in which he would have found the following statements about medicine:

“Some are more reluctant than others to accept immunization, but it is rare that an Amish person will cite a biblical text to object to a demonstrated medical need…” ….””If the Amish are slow to accept preventive measures, it doesn’t mean they religiously opposed to them…”

He might have made more than a cursory effort to contact people at the Clinic for Special Children in Strasburg, Pennsylvania. The Clinic, aside from serving special needs children (including autistics) runs vaccine clinics and has for some many years. In a piece explaining Mr. Olmsted’s failures, Mark Blaxill (also of the Age of Autism) explained that the Clinic did not return Mr. Olmsted’s phone call. No mention is given why Mr. Olmsted didn’t go to the clinic in his visits to Lancaster County

Had Mr. Olmsted done so, he would have known that this statement, again from his 2005 piece, was incorrect when he relied on a source who claimed a very low immunization rate:

That mother said a minority of younger Amish have begun getting their children vaccinated, though a local doctor who has treated thousands of Amish said the rate is still less than 1 percent.

He also made a misleading statement:

When German measles broke out among Amish in Pennsylvania in 1991, the CDC reported that just one of 51 pregnant women they studied had ever been vaccinated against it.

What is left vague in this statement was the fact that the 51 pregnant women were those who contracted German measles. Not surprising that those infected were largely unvaccinated. This doesn’t tell us what fraction of the whole population were vaccinated though, and is quite misleading.

One might wonder why Mr. Olmsted was not aware that the Amish participated in the eradication of Polio. Conversely, he might have questioned how polio was eradicated if the Amish did not vaccinate. Here is a March of Dimes photo from a 1959 vaccine clinic:


(from March of Dimes By David W. Rose, 2003)

An article available to Mr. Olmsted at the time of his 2005 article, Haemophilus influenzae Type b Disease Among Amish Children in Pennsylvania: Reasons for Persistent Disease, discussed the reasons why Amish parents did not vaccinate their children. While some did cite “religious or philosophical objections”, the majority said they would vaccinate if “vaccination were offered locally”:

Among Amish parents who did not vaccinate their children, only 25% (13 of 51) identified either religious or philosophical objections as a factor; 51% (26 of 51) reported that vaccinating was not a priority compared with other activities of daily life. Seventy-three percent (36 of 49) would vaccinate their children if vaccination were offered locally.

Since Mr. Olmsted’s original series, more data has come in refuting the “Amish Anomaly”. In 2006, a paper was published: Vaccination usage among an old-order Amish community in Illinois. Here is the abstract:

The Old-Order Amish have low rates of vaccination and are at increased risk for vaccine-preventable diseases. A written survey was mailed to all Amish households in the largest Amish community in Illinois inquiring about their vaccination status and that of their children. In this survey, the Amish do not universally reject vaccines, adequate vaccination coverage in Amish communities can be achieved, and Amish objections to vaccines might not be for religious reasons.

It is clear that the Amish do vaccinate and that it would have been simple for Mr. Olmsted to find accurate information about this at the time. It was certainly more difficult for Mr. Olmsted to ascertain what the prevalence of autism might be amongst the Amish. He made the assertion: ““there are only a few of them [autistic Amish] in the United States”.

Of the “few” Amish autistics Mr. Olmsted could find, six were being treated by Lawrence Leichtman. The children were unvaccinated but the doctor who reported them to Mr. Olmsted attributed their autism to high mercury levels. This is not surprising as Dr. Leichtman was one of the early alt-med practitioners working in autism, being part of the secretin fad of the 1990’s. One wonders if the “elevated mercury” levels in these children would stand up to tests performed by qualified medical toxicologists.

Another six autistic Amish, nearly under Mr. Olmsted’s nose at the time of his article, were being treated by the Clinic for Special Children in Lancaster, PA. Six children who had PDD or Autism were at that time being treated and written up for a study in the New England Journal of Medicine. They were missed by Mr. Olmsted. He has since argued that these children are syndromic and, thus, somehow not as relevant to his story. Those arguments aside, this was a clear miss for Mr. Olmsted.

In 2010, a study was presented at IMFAR: Prevalence Rates of Autism Spectrum Disorders Among the Old Order Amish

Preliminary data have identified the presence of ASD in the Amish community at a rate of approximately 1 in 271 children using standard ASD screening and diagnostic tools although some modifications may be in order. Further studies are underway to address the cultural norms and customs that may be playing a role in the reporting style of caregivers, as observed by the ADI. Accurate determination of the ASD phenotype in the Amish is a first step in the design of genetic studies of ASD in this population.

A preliminary number of 1 in 271 is a far cry from “little” or no autism amongst the Amish. Given the limitations of working within a community like the Amish, it is surprisingly close to the 1 in 100 often cited as the autism prevalence estimate for the general U.S. population. The study was being prepared for submission when I checked with the lead author last fall. It will be interesting to see what the final number is obtained for the prevalence.

The IMFAR abstract was available, I believe, before Dan Olmsted’s book, The Age of Autism, went to press. Instead of including this information, he chose to paint autism as rare amongst the Amish using quotes he obtained in 2005 and unsupported statements like, “the most aggressive possible count of autistic Amish comes to fewer than 20 cases, which would give us a rate of no more than 1 in 10,000.” It seems unlikely, given the low sales figures, that The Age of Autism will be reprinted. If that should happen, I wonder if Mr. Olmsted will correct this misinformation. The facts are clearly against him. Certainly, his review of internet sources and cursory tour of Lancaster County hardly counts as “aggressive”.

The “Amish don’t vaccinate and don’t have autism” idea was never very well supported. Now, with more data in, it is just plain wrong. It would be a good and honorable thing for Mr. Olmsted himself to make this clear. Good. Honorable. And not going to happen.

Prevalence of Autism Spectrum Disorders in a Total Population Sample

9 May

A long-awaited study of autism prevalence in Korea came out today in the American Journal of Psychiatry. Most of the information we have about autism prevalence comes from the US, the UK and Europe, so many were looking at this as the “Korean Study”. It is that, and very much more.

The title of the study is Prevalence of Autism Spectrum Disorders in a Total Population Sample. I expect the study will be gathering quite a lot of press as the results are quite remarkable. For one thing, the autism prevalence is estimated at 2.64%. That’s right, over double the current estimates in the United States and the U.K.. For another thing, most of the prevalence is for autistic students who were previously unidentified and unsupported.

Unfortunately, I was unable to obtain permission to review the article pre-embargo for discussion here on the Left Brain/Right Brain blog. Instead, I wrote about this for the Autism Science Foundation as Prevalence of Autism Spectrum Disorders in a Total Population Sample. There you will find a more thorough review of the paper, complete with questions and answers with team member Roy Richard Grinker of George Washington University. The study was led by Dr. Young Shin Kim of Yale, and includes an international team:

Young Shin Kim, M.D., Ph.D., Bennett L. Leventhal, M.D., Yun-Joo Koh, Ph.D. , Eric Fombonne, M.D. Eugene Laska, Ph.D., Eun-Chung Lim, M.A., Keun-Ah Cheon, M.D., Ph.D. ,Soo-Jeong Kim, M.D., Young-Key Kim, M.D., HyunKyung Lee, M.A., Dong-Ho Song, M.D., Roy Richard Grinker, Ph.D.

Again, the full post can be found at the Autism Science Foundation blog.

Ageing in autism

6 May

A new paper highlights the issue with geriatric populations in autism.

At present, one of the major challenges is that the majority of the currently older individuals with ASD has not received a formal diagnosis of ASD, and this would be dif?cult to establish using the currently recommended diagnostic assessments, because for many of them, neurodevelopmental history would be hard to obtain. The diagnosis of ASD in children involves both the parents and the child contributing…

You see, nobody working the field of geriatric psychology has any doubt that there is a large population of autistic people within the geriatric population:

Many adult and older subjects with ASD remain undiagnosed and thus are largely unknown to specialist services. [M]any have survived childhood and adulthood by either being fully supported by their family or holding jobs in
protected environment, enabling them to function ‘normally’, and thus escaping the ASD diagnosis. In support for this are the three recent case reports on diagnosing older people with ASD indicating that the standard clinical screenings used in childhood had to be modi?ed and adapted for ?rst?time diagnosis of ASD in older individuals.

As also published recently, it is becoming clearer that there is in fact, no ‘autism epidemic’ and that, in point of fact, research shows:

…nearly one percent of Britons older than 16 years have autism, a rate that is similar to that seen in children. Younger people were no more likely to be affected than older ones, however, which would have been expected if the condition were truly on the increase.

So what can we take from this? Being who I am and having the interests I have I take two main things:

1) Vaccines haven’t caused an epidemic of autism because an epidemic of autism does not in fact exist.

2) There is a large amount of undiagnosed adults with autism who need our help now. They are in community homes (group homes I believe they are referred to as in the US) or living with very elderly relatives. The majority are in situations where their autism is not recognised and not diagnosed. How do we help them?

The University of Newcastle held a Workshop Meeting ‘to reach a consensus on he need for new initiatives in this area.’ and came away with the following points:

1 Prevalence rates of older people with ASD (a prerequisite for planning service needs and placements)
2 Determine life expectancy, behavioural changes and cognitive changes with ageing in ASD
3 Data regarding health problems common in ASD, clinical assessments and treatment of seriously medically ill and frail older individuals with ASD
4 Information whether and how the characteristic clinical symptomatology of ASD change with age
5 Problems diagnosing older individuals with ASD not known to services and development of diagnostic tools for this purpose
6 Diagnosing cognitive impairment and dealing with challenging behaviour in nursing homes
7 Increasing need for advocacy and mental capacity assessments
8 Need to identify services, support and resources for older people with ASD
9 Design of adequate environment for older individuals with ASD
10 Neuroimaging studies in older individuals with ASD
11 Biobanking facilities (cerebrospinal fluid, blood/blood derivates and brain donations) and facilitating research

We should all be aware of the needs of elderly autistic people and try and find a way to help I think. How we should do this is vital. The first step must be the recognition that the idea of an autism epidemic marginalises them.

UK Research places huge question mark over the autism ‘epidemic’

3 May

Just a quick couple of quotes as I’m in a rush.

Researchers found nearly one percent of Britons older than 16 years have autism, a rate that is similar to that seen in children. Younger people were no more likely to be affected than older ones, however, which would have been expected if the condition were truly on the increase.

Source.

And this – same source.

Fears that the condition is becoming more and more common in children have launched both researchers and parents on a fierce search for the underlying reasons.

So far those efforts haven’t paid off, however, and the much-reported claim that childhood vaccines could be the culprit has been widely discredited.

…

“None of them had been diagnosed (previously) with autism,” he said. “I think for me the issue is that people have been ignoring autism in adulthood and only focusing on children.”

California’s Specific Learning Disabilities Counter Epidemic

19 Feb

The U.S. and California Departments of Education recently released special education data (child counts) for the 2008-2009 school year. A particular focus in the media has been a tripling of the number of students who wear a special education label of “autism” in California.

Needless to say, some probably see this as confirmation of an “autism epidemic”. For a particularly myopic and emotional (anger and fear) interpretation of this recent news story, one need go no further than “Autism Epidemic” central (AoA) and read the data-free opinion piece by Anne Dachel.

For the bigger picture in California, a look at the actual data might be in order.

California Data

For those who may not be able to see the graph of the IDEA data that most closely represents the K-12 age group as a percentage of the resident population, receiving special education services for the last ten years in California: Autism has steadily increased from .13% to .64%, Specific Learning Disabilities has steadily decreased from 5.64% to 4.41%, and totals for all disabilities has remained flat at about 9.2%.

If you believe there’s been an “autism epidemic”, and that special education data from California proves that the schools are overwhelmed, here are a two questions for you:

1. What has caused the decrease in Specific Learning Disabilities (a decrease that more than offsets the increase in autism)?

2. If the special education totals remain unchanged, why are the schools “overwhelmed”?

A Comparison of Autism Prevalence Trends in Denmark and Western Australia.

15 Feb

I bring this up because there is a common argument that the autism “rates” in places like Denmark and Sweden are much lower than those in the US and elsewhere. This is used to try to negate studies using those country’s populations in, for example, showing that there is no increased risk from thimerosal or the MMR vaccine. This error often stems from comparing “incidence” to “prevalence”.

Is the autism prevalence low in Denmark? Not really. This paper just out (and other reports previously, including this one cited by Steven Novella) show a prevalence pretty comparable to the US.

J Autism Dev Disord. 2011 Feb 11. [Epub ahead of print]
A Comparison of Autism Prevalence Trends in Denmark and Western Australia.

Parner ET, Thorsen P, Dixon G, de Klerk N, Leonard H, Nassar N, Bourke J, Bower C, Glasson EJ.

Institute of Public Health, Department of Biostatistics, University of Aarhus, Aarhus, Denmark.
Abstract

Prevalence statistics for autism spectrum disorders (ASD) vary widely across geographical boundaries. Some variation can be explained by diagnostic methods, case ascertainment and age at diagnosis. This study compared prevalence statistics for two distinct geographical regions, Denmark and Western Australia, both of which have had population-based registers and consistent classification systems operating over the past decade. Overall ASD prevalence rates were higher in Denmark (68.5 per 10,000 children) compared with Western Australia (51.0 per 10,000 children), while the diagnosis of childhood autism was more prevalent in Western Australia (39.3 per 10,000 children) compared with Denmark (21.8 per 10,000 children). These differences are probably caused by local phenomena affecting case ascertainment but influence from biological or geographical factors may exist.

Prevalence of 68.5 per 10,000 children. A previous estimate was 80 per 10,000. Generation Rescue claimed a rate of 1 in 2200 (4.5 per 10,000) when they tried to make the case that…oh I bet you can guess…that vaccines cause autism. The 1 in 80 figure was already published, so I doubt they will change their story given yet another study.

Seth Mnookin on CNN “American Morning”

11 Jan

The Panic Virus, a book by Seth Mnookin came out today. Mr. Mnooking was interviewed for CNN’s “American Morning”. I agree with much of what he has to say: the “debate” is not balanced. It’s a few people vs. a ton of data and many more people. It is good that the vaccine-autism hypothesis was tested, but it is time to move on.

http://i.cdn.turner.com/cnn/.element/apps/cvp/3.0/swf/cnn_416x234_embed.swf?context=embed&videoId=bestoftv/2011/01/11/exp.am.intv.holmes.mnookin.cnn

Autism ‘levelling off’?

3 Nov

A new paper in Pediatrics asks:

…whether the increasing prevalence of autism, on the basis of educational data, in Wisconsin between 2002 and 2008 was uniform in all school districts or was greatest in districts with lower baseline (2002) prevalence.

In other words, was there a greater increase in the school districts where the prevalence of autism had previously been lowest? In this ‘catch up’ scenario, there was _still_ no epidemic of autism just a gradual levelling out as the school districts with lower prevalence in 2002 ‘caught up’ with the school districts with the higher prevalence in 2002.

In order to answer this question, the authors

…grouped [the districts] into 8 categories (octiles) according to their baseline prevalence, and prevalence trends were plotted according to octile.

The results were as expected – whilst the _overall_ prevalence increased from 4.9 cases per thousand to 9 cases per thousand, in each different octile, the results were not uniform. If an octile already had near 9 cases per thousand then they increased by a very small amount. If an octile was closer to the 4.9 starting point then they increased over the same amount of time (2002 – 2008) by a much larger amount until both reached the same amount – roughly 1%.

As we know from other studies, a prevalence of 1% seems to be emerging from differing areas of the world as well as different areas of the US. As John Harrington states in a companion commentary, this study shows

There seem to be no “hot spots” or high-risk areas with some ominous environmental toxin that can be postulated; it is more likely that educational services for autism were better coordinated in 1 area versus another.

Autism services are playing catch up in the school system in the US according to this paper. Thats all. Still no epidemic.

Social Demographic Change and Autism: part 2

3 Oct

Prof. Peter Bearman’s group is studying the causes for the rise in autism prevalence, using data from the California Department of Developmental Services. I recently wrote a rather long introduction to their recent paper, Social Demographic Change and Autism.

The study abstract is here:

Social Demographic Change and Autism
Liu K, Zerubavel N, Bearman P.

Abstract

Parental age at child’s birth–which has increased for U.S. children in the 1992-2000 birth cohorts–is strongly associated with an increased risk of autism. By turning a social demographic lens on the historical patterning of concordance among twin pairs, we identify a central mechanism for this association: de novo mutations, which are deletions, insertions, and duplications of DNA in the germ cells that are not present in the parents’ DNA. Along the way, we show that a demographic eye on the rising prevalence of autism leads to three major discoveries. First, the estimated heritability of autism has been dramatically overstated. Second, heritability estimates can change over remarkably short periods of time because of increases in germ cell mutations. Third, social demographic change can yield genetic changes that, at the population level, combine to contribute to the increased prevalence of autism.

They start by noting their group’s previous work which showed an increased risk for autism based on both maternal and paternal age.

There is a strong relationship between parental age and autism. The one study (King et al. 2009) that decomposes maternal and paternal age—and confounding cohort effects— identifies maternal age as riskier than paternal age (using the California data deployed in this analysis).

Relative risks were as high as 1.8. These are not as high as the increased risk for Down Syndrome, which can be 10x higher in older mothers, but it is still a notable effect.

The authors note that parental age has increased notably during the 1990’s, the same time that the “autism epidemic” started.

… the proportion of children born whose parents were age 35 or older at birth increased rapidly: from 24.3% in 1992 to 36.2% in 2000.

Many factors have been identified as correlated to the autism increase. Basically anything that increased over the 1990’s could be argued to be correlated with an increase in autism prevalence. Correlation is not causation, as we hear over and over. One must go beyond correlation in order to claim that there is a real effect.

And Prof. Bearman’s group does go beyond correlation. They look at autism in twins and siblings and show that (1) the concordance is much lower than has been previously reported and (2) the concordance is changing with time. They go into detail on the methods in the paper, including how to determine how many twins were “identical” (monozygotic or MZ) vs. fraternal dizygotic or DZ). Here is the table showing the concordance for twins and sibling pairs from the paper, Casewise and Pairwise concordance numbers are given.

Casewise concordance (Pcw) measures the probability that a co-twin will be affected (with a given disorder), given that the other twin is affected. Pairwise concordance (Ppw) measures the proportion of concordant (both twins are affected) pairs in all pairs with at least one twin who is affected.

Pairwise concordance is what most people think of as concordance.

The pairwise concordance is 40% for MZ (identical) male twins and 50% for female twins. Much lower than the higher values from previous, smaller studies which claimed 36-90% concordance. From the paper from Prof. Bearman’s group:

The Evidence for High Heritability of Autism
To date, the strongest evidence supporting the idea that autism is a genetic disorder arises from twin and family studies. Previous twin studies on full syndrome autism have reported high pairwise concordance rates in identical (MZ) twins (36%–96%) and low concordance rates in fraternal (DZ) twin pairs (0%–31%) (Bailey et al. 1995; Folstein and Rutter 1977; Ritvo et al. 1985; Steffenburg et al. 1989). Because MZ twins share 100% of their genes while DZ twins share only around 50%, a large difference between MZ and DZ concordance rates is regarded as strong evidence for genetic infl uences. The recurrence risk of autism in siblings is reported to range from 3%–9%, which is much higher than the population rate of 10 in 10,000 children (Baird and August 1985; Bolton et al. 1994; Piven et al. 1990; Ritvo et al. 1989).3 Relatives of a child with autism are also more likely to have broadly defined autism spectrum traits than controls (Szatmari et al. 2000).

Low concordance is consistent with another recent study, Genetic variance for autism screening items in an unselected sample of toddler-age twins, from Prof. Goldsmith’s group at U. Wisconsin. The abstract is below:

OBJECTIVE: Twin and family studies of autistic traits and of cases diagnosed with autism suggest high heritability; however, the heritability of autistic traits in toddlers has not been investigated. Therefore, this study’s goals were (1) to screen a statewide twin population using items similar to the six critical social and communication items widely used for autism screening in toddlers (Modified Checklist for Autism in Toddlers); (2) to assess the endorsement rates of these items in a general population; and (3) to determine their heritability.

METHOD: Participants composed a statewide, unselected twin population. Screening items were administered to mothers of 1,211 pairs of twins between 2 and 3 years of age. Twin similarity was calculated via concordance rates and tetrachoric and intraclass correlations, and the contribution of genetic and environmental factors was estimated with single-threshold ordinal models.

RESULTS: The population-based twin sample generated endorsement rates on the analogs of the six critical items similar to those reported by the scale’s authors, which they used to determine an autism threshold. Current twin similarity and model-fitting analyses also used this threshold. Casewise concordance rates for monozygotic (43%) and dizygotic (20%) twins suggested moderate heritability of these early autism indicators in the general population. Variance component estimates from model-fitting also suggested moderate heritability of categorical scores.

CONCLUSIONS: Autism screener scores are moderately heritable in 2- to 3-year-old twin children from a population-based twin panel. Inferences about sex differences are limited by the scarcity of females who scored above the threshold on the toddler-age screener.

Back to Prof. Bearman’s study: their analysis went deeper, including measures of the pairwise concordance for non “identical” twins. Opposite sex twins have a 10% concordance, and same sex twins (dizygotic) have 20% concordance. That gender difference in concordance is quite notable.

The risk of having an autistic child is much higher if one already has an autistic child. The recurrance risk is about 10% for full siblings, 3% for half siblings. These values are quite high considering that the autism (not ASD, but autism) prevalence is less than 1%. The recurrence risk is much higher for siblings of an autistic female than autistic male. Male siblings of a female “proband” have a recurrence risk of 18%. Female siblings of a male “proband” have much lower recurrence risk of 5%.

Prof. Bearman’s group has done what may be a first in concordance studies: analyzed data as a function of birth year. “Temperal concordance”. I.e. they ask the question, does the concordance change with time? The answer, yes.

Here are panels (A) and (B) from Figure 1 of the paper.

Panel (A) shows casewise temporal concordance. Concordance increases for single-sex (SS) twins, and decreases for other-sex (OS) twins during the 1990’s. The authors note this is consistent with a de novo mutation mechanism for increased risk for autism. Panel (B) shows that the average age for the twin parents is also increasing over this time period. From the paper:

In panel B, we report change in mean parental age at twin births, which increases steadily during the same period. Recall that because MZ twins are developed from a single pair of matched egg and sperm cells, any de novo mutations will be found in both twins. In contrast, DZ twins develop from two distinct pairs of egg and sperm cells. Because de novo mutations are rare events, the chance that both DZ twins will share the same de novo mutation is extremely low. If de novo mutations have an increasing causal share in the etiology of autism over time, we should expect an increase in the difference between MZ and DZ concordance rates. One mechanism that accounts for de novo mutations’ increasing share of autism etiology is the rise in parental age over our study period, which is likely to lead to increased mutation rates.

One question that naturally arises in regards to multiple births is the use of assisted reproduction technology (ART). The authors discuss this:

Although the genetic influence on autism has been overestimated, it has increased over time due to non-allelic mechanisms. Although the human gene pool does not change substantially over one or two generations, de novo germ-line mutation rates are much more susceptible to rapid social and/or environmental changes (such as rising parental age), and thus can explain the increase in the heritability of autism. Of importance is the fact that although age of parents at birth of twins was signifi cantly higher in 2000 than in 1992, age of parents at the birth of their second-born did not increase over the same period. Thus, the difference between the trends of OS twin concordance and full-sibling recurrence risk may be associated with age of parents. Since the use of assisted reproductive technologies (ART) is associated with the age of parents and has increased radically over the same time period, ART may be implicated in the increased prevalence of autism. Our data show that the increase in the percentage of children with autism born in multiple births (from 3.6% in 1992 to 5.7% in 2000) exceeded that of the percentage of multiple births in all births in California (from 2.1% in 1992 to 2.9% in 2000). This implication requires future investigation.

The risk of autism is higher with multiple births and increased at a greater rate than the percentage of multiple births in general.

The authors discuss the possibility of prenatal exposures to infection or toxicant or a gene/environment interaction might follow the same trends they observe:

It remains possible that other factors have contributed to the diverging trends in the SS and OS concordance. A virus or a toxicant experienced in utero could yield the results that we observe. Specifically, an increasingly prevalent virus (or toxicant) associated with a small risk of autism would lead to increasing concordance of SS twins (who often share the same placenta) and decreasing concordance of OS twins. Similarly, interactions between genes and an increasingly common environmental trigger could also generate the same pattern. However, we believe that an increase of de novo mutations attributable to rising parental age is more parsimonious given the documented rise in parental age, recent findings that link de novo mutations and autism, and the observed associations between concordance rates and parental age reported in this article.

The authors address one concern that I had in reading the paper: what if some change in the way children are qualified for regional center services changed the characteristics of their population. Or, to put it more simply, are the autistics in 2000 really comparable to those in 1990? Regional center data show a decreasing percentage of children also in the mental retardation and epilepsy categories. Could this have an effect on their results? From the paper:

The temporal concordance trend reported in this article is not predicted by a diagnostic expansion theory. If ascertainment and surveillance dynamics rest behind the increase in SS concordance, we would expect to observe increasing rather than decreasing concordance for OS twin pairs over time. The observation of decreasing concordance over time in OS twins challenges the idea that the results we observe are an artifact of reduction of error in diagnosis as a consequence of enhanced surveillance or clearer understanding of diagnostic markers. First, there is no evidence that diagnostic errors have been reduced; second, if this were the case, we should observe the same effect across all pair types. Finally, increasing ascertainment and surveillance would predict heightened recurrence risk for siblings over time. We do not observe any increase in such risk (chi-square statistics of linear trends in proportion = 1.613; p = .204).

The authors’ concluding paragraph is:

For social scientists, there are three important discoveries. First, we show that a sociological eye on the role of genetics yields the insight that de novo mutations may play a signifi cant role in autism etiology. Only by observing changing patterns of concordance over time—that is, historicizing genetic influences rather than essentializing them—could we find evidence of a new causal mechanism underlying autism. Second, by working with a large population-based data set, versus small clinical samples, we have been able to properly estimate the true heritability of autism. These estimates show that autism is far less heritable than previously thought and consequently, explanations for the precipitous increase in prevalence must turn toward environmental and social dynamics often ignored by the scientific research community. Third, we show that the identification of the mechanisms by which social processes operating at the macro level—in this case, increases in parental age—“get under the skin” and shape health outcomes is a proper social science activity.

This study has the possibility to have a major impact on autism causation research. I would not be surprised at all if this ends up as one of the papers highlighted by the IACC for the year. I’m certain that this paper will be brought up in online discussions for some time to come, what with the very different estimate of twin concordance than previously quoted.

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