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Los Angeles Times: Discovering Autism

23 Dec

The Los Angeles Times produced a series of articles called “Discovering Autism”. The series is in four parts and represents was researched for years. The articles are:

Autism boom: an epidemic of disease or of discovery?
Autism rates have increased twentyfold in a generation, stirring parents’ deepest fears and prompting a search for answers. But what if the upsurge is not what it appears to be?

Warrior parents fare best in securing autism services
Public spending on children with autism in California varies greatly by race and class. A major reason: Not all families have the means to battle for coveted assistance.

Families cling to hope of autism ‘recovery’
An autism treatment called applied behavior analysis, or ABA, has wide support and has grown into a profitable business. It has its limits, though, and there are gaps in the science.

Autism hidden in plain sight
As more children are diagnosed with autism, researchers are trying to find unrecognized cases of the disorder in adults. The search for the missing millions is just beginning.

The first article brought a great deal of criticism, from many quarters. As you can imagine challenging the way the “autism epidemic” is viewed is not welcomed by those promoting vaccines as a primary cause of autism. This article also brought out at least one commenter who asserted that the rise in autism diagnoses is driven by people seeking social security payments (SSI), which goes to show that readers tend to bring their own preconceptions to what they read.

Interest in the online discussion of the series dropped off dramatically after day one.

Autism boom: an epidemic of disease or of discovery? looked at the rise in autism diagnoses observed in many places. Writer Alan Zarembo points out quite rightly that autism rates vary dramatically by school district in California, as well as state to state.

Such variability of autism rates across geography speak strongly against the idea of a single cause, such as vaccines. Autism Diva wrote about the strong variation by regional center district within California years ago (her piece is not up, but this article from LBRB discusses her article)

The variation by school district and by race/ethnicity was a major factor in helping me see that the vaccine-epidemic of autism did not make sense, back when I first started to read up on autism.

The LA Times quotes Prof. Peter Bearman of Columbia University, who studied the California Department of Developmental Services data closely and showed, amongst other things, that a large autism “cluster” existed in Southern California. The Times notes that similar clusters were found by U.C. Davis Professor Irva Hertz-Picciotto. (I was present when Autism Diva discussed the regional center graph with Prof. Hertz-Picciotto, by the way).

Prof. Bearman also showed that social forces were at work–awareness, if you will–which has aided the increase in autism diagnoses.

In other words, autism is not contagious, but the diagnosis is.

“`Is it real or not?’ is a meaningless question,” Bearman said of the surge in cases. “The sociological processes are as real as the biological processes.”

A diagnostician (neurologist) is quoted in the Times:

Dr. Nancy Niparko, a child neurologist in Beverly Hills, said that whether she identifies a child as autistic can come down to whether she believes it will do any good.

“If it’s going to improve the possibility of getting services that will be helpful, I will give the label,” she said.

“I don’t work for labels. Labels work for me.”

In Warrior parents fare best in securing autism services makes the point that it takes work, hard work, to get the services that a child may need. An autism diagnosis is not a ticket to services, it is a first step. Parents who fight harder and longer tend to get higher levels of services for their children.

The Times points out that within a single district (albeit one of the largest in the U.S., Los Angeles Unified), the fraction of students with 1:1 aides varies by geography and race/ethnicity:

District officials acknowledge that advocacy efforts make a big difference in who gets services, but see things differently than parents on the value of 1:1 aides:

L.A. Unified officials offered a similar explanation for the disparity. As parents successfully lobbied for outside aides, the idea spread, and in certain schools it became standard practice to offer them.

“Parents learned from each other,” said Nancy Franklin, a top special education administrator. “It became a cottage industry in LAUSD.”

The district is trying to break the pattern by persuading parents that its own staff can meet children’s needs in many cases.

“We’re paying lots of money for services that are of questionable value,” said Eileen Skone-Rees, who oversees the district’s contracts with companies that supply one-on-one aides.

In Families cling to hope of autism ‘recovery’, the Times focuses on ABA. Biomedical approaches are not really discussed.

The article talks about ABA from the early work of Ivar Lovaas to the present day, where it is common in some school districts and regional centers. The high costs and the level of research support are discussed along with examples of children who are success stories and those who are not.

In Autism hidden in plain sight, the Times looks at how autism is often missed in adults.

The Times presents an intriguing look at the past in medical records from a child diagnosed by Leo Kanner (whose work coined the term “autism”).

The times provided a number of slide show vignettes of people they interviewed.

I can’t link to them directly, but I’ve watched a few and enjoyed them. Jeane Duquet, autistic adult diagnosed at age 39 (right side, middle). Jesse Castillo, age 11 (bottom right corner)

The author of the series, as well as Catherine Lord were interviewed by NPR:

http://www.npr.org/v2/?i=144022386&m=144022377&t=audiowidth=”400″ height=”446″ />

I would certainly have done some things differently had I written the series. I would have chosen different wording, for example. Yes, the pieces brought out some less than pleasant perspectives. I’ve read a few complaints about the series, from not supporting vaccine causation or biomedical approaches to presenting autism as a costly burden. Ironically, these complaints come from the same people who repeatedly say that “autism costs society $3.5 million per individual”. A big piece of that $3.5M is ABA and if we as a community (or part of the community) are to defend the need for ABA, we have to accept that there is a cost. I believe, and I commented, that the choice of language at times put a negative slant where one was not needed. However, the series put some very good information out, including: 1) the “epidemic” has a large portion which is driven by social factors, with a much smaller part that may be a real change in the number of autistics, 2) services are not handed out on a silver platter. Parents and autistics have to fight for what supports the law says they should get, 3) 1:1 therapies such as ABA may be effective, but they are expensive and the research behind them is still incomplete and 4) adult autistics are out there in greater numbers than is currently reported.

The biggest complaint about the series is that it portrays parents as seeking diagnoses for their kids for some sort of financial gain. Dr. Jay Gordon (a major promoter of the vaccine-epidemic idea) has noted this where Mr. Zarembo has been interviewed (http://www.scpr.org/programs/patt-morrison/2011/12/22/21866/autism-diagnoses-spike-an-epidemic-in-the-making). Mr. Zarembo makes it clear in the interview that this is not his point. That the autism diagnosis “opens the door” and that parents are doing what they should for their children–including fighting hard to obtain appropriate services once the door is opened.

For those complaining that the LA Times series didn’t cover the vaccine-epidemic idea or biomedical approaches to autism: I’d recommend you be thankful. Quite frankly an evidence driven newspaper series on these issues will not go the way you want.

Increased autism risk found in closely spaced pregancies

10 Jan

Prof. Peter Bearman is the Jonathan Cole Professor of the Social Sciences at Columbia University. His team has been delving in-depth into the California Department of Developmental Services (CDDS) data on autism.

There are some big caveats to using the CDDS data. These include:
The CDDS dataset is based on administrative prevalence. In other words, it is a listing of individuals who sought and were successful getting services. It is not a listing of all autistics in California and it the standards of inclusion are not standardized over time and geography.

In terms of shear size, it is probably the largest such dataset in the U.S.. So, taking the limitations to heart, it is worth taking a look at what one can do with these data.

The authors note this:

Use of administrative records of the California DDS for identification of autism represents a strength of the study, facilitating population-based analyses over 11 years of birth records from this populous and diverse state. However, inclusion as a case subject depends on seeking services and receiving a qualifying diagnosis, with previous reports estimating that 75% to 80% of people with autism in California register with the DDS.

The authors are: Keely Cheslack-Postava, PhD, MSPH, Kayuet Liu, DPhil, and Peter S. Bearman, PhD.

The team took the data and asked, is there an increased risk of autism for children based on how long the parents waited after a previous birth?

Consider second-born children. If a mother gets pregnant right after her first born, is the risk of autism the same, greater or less than if she waits? Based on what they found, the Columbia group would say that the risk is higher if the mother gets pregnant again shortly after giving birth.

Here is a blurb on the study:

INCREASED AUTISM RISK FOUND IN CLOSELY SPACED PREGNANCIES
 
An examination of California birth records found second-born children were more than three times more likely to be diagnosed with autism if they were conceived within 12 months of the birth of their older sibling. The farther apart pregnancies were spaced, the lower the risk of autism. The study, “Closely Spaced Pregnancies Are Associated With Increased Odds of Autism in California Sibling Births” published in the February 2011 issue of Pediatrics (published online Jan. 10) examined the odds of autism among more than 660,000 second-born children. Compared to children who were conceived more than three years after the birth of an older sibling, children conceived after an interpregnancy interval (IPI) of less than 12 months were over three times more likely to be diagnosed with autism. Children conceived after an IPI of 12 to 23 months were 1.86 times more likely to have been diagnosed with autism, and children conceived after an IPI of 24 to 35 months were 1.26 times more likely to have been diagnosed with autism.
 
One possible explanation for the increased risk of autism is that women are more likely to have depleted levels of nutrients such as folate and iron, as well as higher stress levels, after a recent pregnancy; however, these factors were not tested in the current study. Study authors suggest the finding is particularly important given trends in birth spacing in the U.S.; between 1995 and 2002, the proportion of births occurring within 24 months of a previous birth increased from 11 percent to 18 percent. Closely spaced births occur because of unintended pregnancies but also by choice, particularly among older women who delay childbearing. The study was funded by the NIH Director’s Pioneer Award Program.

Here is the abstract:

OBJECTIVE: To determine whether the interpregnancy interval (IPI) is associated with the risk of autism in subsequent births.

METHODS: Pairs of first- and second-born singleton full siblings were identified from all California births that occurred from 1992 to 2002 using birth records, and autism diagnoses were identified by using linked records of the California Department of Developmental Services. IPI was calculated as the time interval between birth dates minus the gestational age of the second sibling. In the primary analysis, logistic regression models were used to determine whether odds of autism in second-born children varied according to IPI. To address potential confounding by unmeasured family-level factors, a case-sibling control analysis determined whether affected sibling (first versus second) varied with IPI.

RESULTS: An inverse association between IPI and odds of autism among 662 730 second-born children was observed. In particular, IPIs of 36 months. The association was not mediated by preterm birth or low birth weight and persisted across categories of sociodemographic characteristics, with some attenuation in the oldest and youngest parents. Second-born children were at increased risk of autism relative to their firstborn siblings only in pairs with short IPIs.

CONCLUSIONS: These results suggest that children born after shorter intervals between pregnancies are at increased risk of developing
autism; the highest risk was associated with pregnancies spaced <1 year apart. Pediatrics 2011;127:000

Simply put, they claim that indeed there is an increased risk of autism if a follow-on pregnancy comes shortly after the first. In fact, the odds of having an autistic child are

Here is Figure 2 of the paper. This shows their computed odds ratio as a function of IPI–inter-pregnancy interval.

The authors conclusion is:

This study provides evidence of an inverse association between IPIs and autism risk, with a more than threefold elevated odds in pregnancies conceived within a year of a previous birth. This finding is particularly important given trends in birth spacing in the United States. Between 1995 and 2002, the proportion of births occurring within 24 months of a previous birth increased from 11% to 18%. Closely spaced births occur in some part because of unintended pregnancies but also by choice, particularly among women who delay childbearing. Therefore, additional research to confirm this association in other populations and to undercover underlying mechanisms is particularly critical.

As with any study like this, replication is critical. But, if there isn’t some unkown artifact at play here, this could point to more information on causation in autism.

Age of diagnosis for autism: individual and community factors across 10 birth cohorts

6 Nov

Prof. Peter Bearman’s group at Columbia has a new paper out: Age of diagnosis for autism: individual and community factors across 10 birth cohorts.

The study looks at children receiving services from the California Department of Developmental Services (CDDS). The CDDS dataset is not a “census” of autistics in California, but is a registry of those who have sought services, have been identified as autistic and and who have been granted services. Factors which can affect who seeks services for their children, who seeks and how easy it is to identify an autistic child (e.g. access to people who can do the diagosis) will have an effect on who is identified and when that person is identified.

As an aside, I focus on autistic children here because the study does. The authors focused on those identified who were under age 8. They did this to make the comparisons consistent across birth cohorts. For example, one can’t look at 15 year olds born in the year 2000.

Age of diagnosis was taken as age of autism into the entry for the child into the CDDS registry. This can occur either when the child undergoes an intake or a change in the child’s status occurs (say, a diagnosis of autism is given to a child already in the CDDS system)

California statutorily requires that regional centres confirm eligibility for services, including verifying or conferring a diagnosis, within 120 days of intake, so the date at which DDS clinicians either provided or confirmed a first diagnosis of autism is within a few months of caregivers’ initial request for assistance. Combined with the child’s date of birth, we then used the date of entry from the first available CDER to calculate the age of diagnosis. Diagnoses earlier than age 3 years are empirically rare, as infants and toddlers below 36 months with suspected developmental delays and those considered at risk are served by the early start programme.

I don’t have the data, but my very anecdotal and likely biased experience is that currently diagnoses earlier than 36 months are not rare at all.

Prof. Bearman’s group shows that the age of diagnosis steadily dropped during the 1990’s, from 4.4 years of age in 1992 to below 3.4 years of age in 2002. Here’s the figure from the paper (click to enlarge):

Non-White and Hispanic children were diagnosed later. Children of highly educated parents were diagnosed earlier. Both of these effects remained throughout the time span considered (1992-2002). Children of mothers born outside the US and first born children were diagnosed later, but this effect disappeared over time. Children with better communication skills were diagnosed later.

They also found that the age of diagnosis depends on the parents socio-economic status (ses). As one might predict, better off families got diagnoses for their children earlier. Here is the figure showing the trend of age-of-diagnosis vs. birth year for low and high ses:

It is good to see the gap decreasing with time, but it shouldn’t be there at all.

One obvious question that comes up from this study–a question that it can not answer–is how many people are never correctly diagnosed, and what gap might there be in that number based on ses?

The full paper can be found on Prof. Bearman’s team website. Here is the abstract:

Background The incidence of autism rose dramatically between 1992 and 2001, while the age at which children were first diagnosed declined. During this period the size and composition of the autism caseload has changed, but little is known about whether the factors associated with the timing of diagnosis may also have shifted. Using a multilevel analysis strategy, the individual and community-level factors associated with age of diagnosis were modelled across 10 birth cohorts of California children.

Methods Linked birth and administrative records on 17?185 children with diagnoses of autistic disorder born in California between 1992 and 2001 and enrolled with the California Department of Developmental Services (DDS) were analysed. Information on cases, their parents and their residential location were extracted from birth and DDS records. Zip codes of residence were matched to census data to create community-level measures. Multilevel linear models were estimated for each birth cohort, with individual-level effects for sex, race, parental characteristics, poverty status, birth order and symptom expression. At the community level measures of educational and economic composition, local autism prevalence and the presence of a child psychiatrist were included.

Results Children with highly educated parents are diagnosed earlier, and this effect has strengthened over time. There is a persistent gap in the age of diagnosis between high and low socioeconomic status (SES) children that has shrunk but not disappeared over time.

Conclusion Routine screening for autism in early childhood for all children, particularly those of low SES, is necessary to eliminate disparities in early intervention.

Here is the press release for the study.

Autism is diagnosed later for children with less educated parents
A Columbia study, appearing this week in the Journal of Epidemiology and Community Health, has found a gap in age of diagnosis for autism between children of high and low socioeconomic status in California. This gap has become smaller over time, falling from about fourteen months to about six months in a decade, but it remains significant. The strongest factor in this gap was parental education. Children of highly educated parents tend to be diagnosed at earlier ages, and this effect has not diminished over time.

The findings suggest that although the median age of diagnosis for autism has dropped from about four and a half years in the early 1990s to about three and a half in the 2000 birth cohort, there are some groups of children who are still diagnosed late. Diagnosis is the crucial first step to treatment, widely believed to be most effective at younger ages, and even six months may be important at an age when children are developing rapidly. “Our findings point strongly to the idea that some children may be at a great disadvantage when it comes to access to diagnosis and treatment for autism,” said Peter Bearman, the Jonathan Cole Professor of the Social Sciences and principal investigator of the paper. “These delays may have important consequences for later behavioral and cognitive outcomes.”

Autism impairs social interaction and predisposes children to restrictive and repetitive behaviors. Over the past two decades California has witnessed a particularly large spike in autism cases. Between 1992 and 2006, the state’s caseload increased 598 percent. At the same time, the typical age of diagnosis has dropped from school-age to the early pre-school years.

This study was based on 17,185 children with autism born in California from 1992-2001. In addition to looking at characteristics of the children and their parents, from the birth records, the researchers used the zip code at birth and diagnosis to examine the characteristics of the communities in which the children lived.

The researchers found that children born to less-educated mothers, and those whose births were paid for by Medi-Cal (California’s Medicare program) were diagnosed later. In addition, non-White and Hispanic children, and those with mothers born outside the US, showed delayed diagnosis. In the early part of the decade, firstborn children were also diagnosed later, suggesting that parental familiarity with typical child development may have been a factor, however this effect disappeared over time as autism awareness spread.

The kinds of neighborhoods where children lived also mattered, particularly in the early years of the study. In these years, children living in areas that had many children with autism were diagnosed early, which indicates that familiarity with the symptoms of autism may have been important. Children born in neighborhoods with higher property values were also diagnosed earlier. In general though, over time the importance of neighborhood characteristics seems to have diminished, perhaps because autism became more visible and recognized.

“The findings suggest that for many children, increasing awareness of autism and regular screening has succeeded in indentifying cases of autism at earlier ages,” said Christine Fountain, postdoctoral researcher and lead author of the paper. “However we need a better understanding of how information about autism spreads between parents, teachers, and physicians, and how parents marshal their resources to obtain diagnoses and services for their children in a timely way. This will help us to make sure that some children aren’t left undiagnosed and without the help that they need.”

The study was supported by a National Institutes of Health Pioneer Grant, given to scientists pursuing new strategies to improve health, and was conducted through Columbia’s Paul F. Lazarsfeld Center for Social Sciences. More information on this study can be found at http://understandingautism.columbia.edu.

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.

Social Demographic Change and Autism: part 1

3 Oct

I’ve been meaning to blog this for a long time. Ever since it came online, which was months ago. I’ve wanted to do a good job on this paper and so I’ve kept putting it off while I wait for the time to really dig into it. Kev’s recent post about Prof. Bearman got me thinking it is time to get this out. I knew this would be long and it has grown longer than I expected, so I have split the post up. Here are some introductory thoughts. Much as people like to paint me as being in the “genetics” camp, it isn’t really my interest. Someone like Prometheus would do a far better job on an intro and discussion that I can. But in Prom’s absence, I will say what I can.

Prof. Peter Bearman is a researcher at Columbia University. His team has taken a very careful look at the California Department of Developmental Services (CDDS) data and combined this with California birth record data and come up with what are likely some of the best papers to come from those data. The CDDS provides services to the developmentally disabled in California through a series of “Regional Centers”, which are private corporations which administer the state’s funding through largely non-governmental agencies in the state. They have records on the people (consumers) whom they have served over the years and these data include information on how the consumers qualify for services.

There are five eligibility categories for regional center support:

1) Mental Retardation: Significant deficits in general intellectual functioning (generally an IQ of 70 or below) and significant deficits in adaptive functioning.

2) Cerebral Palsy: A neurological condition occurring from birth or early infancy resulting in an inability to voluntarily control muscular activity, and resulting in significant deficits in motor adaptive functioning and or cognitive abilities.

3) Epilepsy: A disorder of the central nervous system in which the major symptoms are seizures. Eligibility is based on a seizure disorder that is uncontrolled or poorly controlled , despite medical compliance and medical intervention.

4) Autism: A syndrome characterized by impairment in social interaction (withdrawal, failure to engage in interaction with peers or adults), delays in both verbal and nonverbal communication skills, deficits in cognitive skills, and impairment in the ability to engage in make-believe play. Individuals may engage in repetitive activities or a limited repertoire of activities.

5) Fifth Condition: This category includes disabling conditions found to be closely related to mental retardation or requiring treatment similar to that required for individuals with mental retardation.

As a side note, a lot of people forget the “Fifth Condition” category. People will say that people with Asperger Syndrome or PDD-NOS don’t qualify for Regional Center services. Well, they don’t under the “autism” category, but they can under the fifth condition if they meet the requirements for a “substantial disability”. But, I am digressing.

The CDDS data have been extensively used to demonstrate the very large increase in autism prevalence that has occurred over the last 20-30 years.
Prof. Bearman’s group has studied the CDDS data and found that some of the increase can be found to attributed to factors such as changes in the way people are diagnosed (diagnostic accretion) and lower ages of identification.

In a recent paper, Social Demographic Change and Autism, Prof. Bearman’s group argues that about 11% of the rise in autism prevalence can be attributed to genetics.

Sorry to give away the conclusion so early but this is going to be long and I know a lot of people won’t read it all.

Genetics is a hot-button issue with a lot of people in the online autism community. Sometimes people will divide the world into two camps: those who believe autism is caused by vaccines and those who believe autism is caused by genetics. It is a major oversimplification but it happens.

Another oversimplification is to confuse genetics and heritability. As in, “I’m not autistic and my wife isn’t autistic, genetics doesn’t account for my kid being autistic”. This is wrong on so many counts. Heritability implies genetics, but not all genetics is heritable.

In high school or even earlier you probably learned about a monk and pea plants and later studies on fruit flies and the color of their eyes. This is Mendelian inheritance. You learned that some traits are recessive and some are dominant.

From this framework, you can’t get a genetic epidemic.

Whenever the argument about genes and changing prevalence comes up, you can be sure someone will eventually bring up Down Syndrome. Down Syndrome is a developmental disability (possibly an example of the sort that comprise the “fifth category” in the DDS). Down Syndrome is genetic. Not always Mendelian inheritance genetic, but genetic all the same.

The risk factors for having a child with Down Syndrome are

1) Advancing maternal age. A woman’s chances of giving birth to a child with Down syndrome increase with age because older eggs have a greater risk of improper chromosome division. By age 35, a woman’s risk of conceiving a child with Down syndrome is 1 in 400. By age 45, the risk is 1 in 35. However, most children with Down syndrome are actually born to women under age 35 because younger women have far more babies.
2) Having had one child with Down syndrome. Typically, a woman who has one child with Down syndrome has about a 1 percent chance of having another child with Down syndrome.
3) Being carriers of the genetic translocation for Down syndrome. Both men and women can pass the genetic translocation for Down syndrome on to their children.

Part 2 and 3 are what we usually think of as “genetic”, as in “Mendalian”. But what about (1) advancing maternal age? A 10 times greater risk for older mothers? Keep in mind, there is a clear genetic difference behind Down Syndrome.

In humans, the egg cells and sperm cells have 23 chromosomes. The rest of your cells normally contain 23 pairs of chromosomes — one from your father and one from your mother. Kids with Down syndrome usually have three copies of chromosome 21 — called trisomy 21 — instead of two copies.

There is a difference, some might call it an error, in the genetic sequence which leads to Down Syndrome. The parents don’t need to have it. It can be genetic and not heritable. Or, at least, not heritable in the way most people think.

Parental age is increasing. We would be seeing an epidemic of Down Syndrome if it weren’t for the genetic test that is available and offered to most pregnant women.

There are already studies out discussing increased risk for having an autistic child with parental age. If parental age is increasing (and it is), why don’t we see an epidemic of autism from this?

Add to this the recent study from the Autism Genome Project (which came out after this paper by Prof. Bearman’s group). That study, and others, are showing that rather than an autism “gene”, that copy number variations (CNVs) may be one source of genetic risk for autism. These are not heritable in the usual sense as usually they exist in the child and not the parent.

According to Prof. Bearman, we are seeing it. It accounts for about 11% of the increase in autism prevalence in the CDDS data. It is a big effect, but small compared to the other factors going on (the other 89%). So without a careful look, one can’t show it.

Prof. Bearman’s group *is* taking a careful look. The result is their paper Social Demographic Change and Autism. There are a lot of very interesting results, like twin concordance being much smaller than has been previously reported. Another recent paper confirms that. Strangely, no one seems to have noticed.

I’ll try to rectify that in the next installment when we look closer at the paper. Until then, here is the 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

Katie Wright demonstrates AoA mentality

30 Sep

Over at the Clown Blog, Katie Wright pens a sulky screed targeting Peter Bearman. Lets go through it.

Dr. Peter Bearman, a professor of sociology at Columbia University, recently released a research paper alleging that half of the meteoric rise in ASD cases is an artifact. You know- “better diagnosis” and “greater awareness.” A blind, non-medical professional, could have diagnosed my son. Nevertheless in the case of HF ASD and aspergers (which comprise a small % of overall ASD) certainly greater awareness has played a role in the increasing number of those diagnoses. Still- 50%? Ridiculous.

And why ridiculous? Well….just because. Wright offers no evidence to counteract Bearman’s. No science is referenced to challenge Bearman’s work. It simply is ridiculous apparently. One can almost hear the foot stomp of a poor little rich girl out of her league intellectually.

After Dr. Bearman concludes that 50% of the increase cannot be attributed to greater awareness Insel asks what Bearman believes is driving the other 50%. Bearman answers: “genes, old parents and possibly a virus.” This is the best he has got? The NIH gave this guy millions to come with that?

Well no Katie, thats not what the NIH gave him his research money for. According to _you_ Insel asked Bearman what he _believed_ was driving the other 50%. He gave his answer as to what he _believed_ . But these beliefs were just that – beliefs. He presented the science he had done and then shut up on the evidence and opined and on what he was asked to opine on by Insel.

And even his opinion, his beliefs, are rooted in science. There _is_ a genetic component to autism, thats simply a fact. There _is_ research that links ASD to older parents. Katie Wright’s beliefs revolve around one extremely unscientific thing. Vaccines.

Yes, Bearman does acknowledge the possible role of some kind of toxin. Bearman is not sure what that toxin is but he is sure what it isn’t. Take a guess.

See what I mean. If it ain’t a vaccine, it ain’t worth considering according to Katie Wright.

…unbelievably Bearman says: “it isn’t autism that parents are worried about. They know they can deal with that, they know they can help their child, (and he would know this a non parent of an ASD child?) but it is autism organizations scaring parents!” I had no idea that a bunch of stay at home Moms with no money, no federal backing, no million dollar grants- who are already busy parenting autistic kids- have this kind of extraordinary power! Wow, what’s next for us? Ending the recession, solving the mortgage crisis, creating electric cars?

And hot damn Katie Wright, guess what? In my opinion he _is_ right! I’m not scared of autism. I’m scared of one note zealots stealing away research monies, scaring away legitimate researchers with their threats of violence and scaring the public into believing that autism is some kind of tsunami of evil ready to engulf them all in a tide of social security claims.

As for Katie Wright personally, it makes me sick to think of this little rich girl, who’s children will want for nothing, playing the ‘poor little me’ card. There are families out there struggling to get by on a day to day basis and she has the temerity to liken herself to a ‘stay at home mom’. Feh.

As far as blaming the parents for the national crisis of confidence in vaccine safety- grow up Dr. Bearman. The problem is the problem- not people talking about the problem.

Nice quote from that intellectual giant Jim Carrey there. Oh and guess what Katie Wright? You and people like you *are the problem* . Whilst you play offended at legitimate science, there’s a whooping cough outbreak in California that is killing children. You do know that don’t you Katie Wright?

Here’s what you need to do Katie Wright. You need to accept the fact that the science is against you. You need to accept the fact that you are a small scaremongering minority of the autism community. Sounding off about stuff that you clearly have absolutely zero knowledge about (science) makes you look foolish and all it does is show you to be frightened. You are behind the times. Get out of the way of progress.

Autism researchers want your input: Autism Life Histories at Columbia

17 Sep

Prof. Peter Bearman’s group at Columbia has done and is still doing much in the way of autism epidemiology research. We have discussed many of his group’s papers here on LeftBrainRightBrain. Prof. Bearman’s group now has a website up, Understanding Autism.

As a part of their continuing research into autism, the Bearman team has launched a new project, AutismLifeHistories.org. This is essentially a survey to collect information from parents about their child’s

edit to add–here is how I intended that sentence to read
This is essentially a survey to collect information from parents about their child’s history, but nothing prevents a self-advocate from submitting information on him/her self.

The full description is below, but here is a shorter version from page 1 of the survey:

The purpose of this online survey is to learn about how you recognized your child’s autism, sought professional help and navigated the system of services. We hope that these stories help us arrive at a better understanding of the difficulties of the road to diagnosis and service provision.

While we do not believe that the content and the nature of the questions presented in this survey will cause you any discomfort, your participation is absolutely voluntary throughout the survey. This means that you are free to leave this survey at any time you wish. We will only read your responses if you complete and submit your responses.

It took me about 10 minutes. One could easily spend less.

Here is the longer description of the project:

Autism Life Histories
Dear Parent,

We are researchers at Columbia University’s Institute for Social and Economic Research and Policy studying autism. We are currently collecting life stories from parents about their experiences in recognizing their child’s autism, seeking professional help and navigating the system of services.

The goal of this project is to gain a better understanding of the road to diagnosis. Parents have different experiences and observations of their child’s development and they have different personal resources with which they access care and services. Parents also differ in the type and extent of their support networks and social relations. And finally parents make different decisions in their quest for obtaining the right diagnosis and care for their child. We are eager to hear about how these factors affected your experience and your child’s experience with autism.

We invite you to tell your story by completing a semi-structured survey in which your identity will remain confidential. In fact, this task is less of a survey and more of a conversation between you and us. There are three main sections to this conversation. The first section is set up to learn about you; we ask you a series of short questions. The second section is designed to learn about your child; we ask a series of short questions about his/her age, birth year and place and interaction with other children. The third section provides you with unlimited space to write about your story in recognizing your child’s autism. We hope you will decide to talk with us.

We thank you in advance for taking the time to read through this invitation and look forward to getting to know you. Please feel free to contact us via e-mail at understandingautism@columbia.edu with any questions that you may have. Please be assured that we will not share your story with anyone other than authorized members of our research team. No one else will have access to it.

To share your story, please click on the following link talk-to-us to the online survey.

Sincerely,

Peter Bearman, Principal Investigator
Cole Professor of the Social Sciences

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