Autism Regression: A prevalence study

A review of: Baird, G., Charman, T., Pickles, A., Chandler, S., Loucas, T., Meldrum, D., Carcani-Rathwell, I., Serkana, D., Simonoff, E. (2008). Regression, Developmental Trajectory and Associated Problems in Disorders in the Autism Spectrum: The SNAP Study. Journal of Autism and Developmental Disorders DOI: 10.1007/s10803-008-0571-9

Although most children with autism present very early signs and symptoms and a linear developmental trajectory, a small subset of children present a trajectory characterized by normal development followed by a loss of acquired skills or a failure to use the acquired skills. This pattern has been termed autistic regression. Possible explainations for this phenomenom have varied from a genetic effect on brain restructuring and pruning during the early stages of life, to enterocolitis due to vaccinations, to epilepsy. In this study, the authors explored differences in developmental outcomes for children with and without regressive autism, and the association between regression and enterocolitis and epilepsy. This study examined a population cohort born in the UK in 1990 and 1991. Out of 56,946 children in this cohort, 218 had and ASD diagnosis by age 10. A subset of these children were evaluated via ADOS and ADI and divided into a broad autism (N=105), narrow autism (N=53), and no autism (N=97). The narrow autism group met full criteria for autism based on ICD-10. The broad autism group met clinical consensus for autism but not full ICD-10 criteria. These children were then evaluated for history of epilepsy, gastroinstestinal problems, and developmental regression. 39% of children with narrow autism had a history of regression during development. This compared to 11% of children with broad autism, and 3% of children with no autism. On average this regression occurred around the 25 month of age. There were no differences in IQ or adaptive functioning between those with or without regression. However, those with regression classified in the broad autism group had significantly more symptoms than those without regression also classified in the broad autism group. Regression was not associated with gastroinstestinal symptoms or with epilepsy.

Autism and Parental Psychiatric Disorders

A brief review of: Daniels, J.L., Forssen, U., Hultman, C.M., Cnattingius, S., Savitz, D.A., Feychting, M., Sparen, P. (2008). Parental Psychiatric Disorders Associated With Autism Spectrum Disorders in the Offspring. PEDIATRICS, 121(5), e1357-e1362. DOI: 10.1542/peds.2007-2296

The journal of Pediatrics just published a population study based on the national Swedish registry, which examined the association between parental psychiatric history and autism. The authors compared the parental psychiatric history of 1,227 of children with autism spectrum disorder and 30,925 typically developing children. Children were identified as having autism spectrum disorder if they were born between 1977 and 2003 and had a diagnosis of ASD recorded in the registry between 1987 and 2003.

Parents of children with autism were 70% more likely than parents of typically developing kids to have a psychiatric diagnosis. When both parents had a psychiatric disorder, the children were 100% more likely to have a diagnosis of autism. Schizophrenia was more common in both parents among children with autism as compared to parents of typically developing kids (90% more likely for mothers and 110% more likely for fathers). In addition, mothers of children with autism were more likely than mothers of typically developing kids to have depression (70%), and personality disorders (70%).

In summary, the study suggests that in Sweden, during the last 30 years, children with a diagnosis of autism were more likely to have parents with psychiatric diagnoses than typically developing children. This could reflect a non-specific, possibly genetic, predisposition in affected families for psychiatric conditions, including autism. It could also reflect that having a child with autism increases stress in the parents possibly leading to psychiatric diagnoses. However, the association noted by the authors was even stronger if the parental diagnosis was provided before the child’s diagnosis. One important consideration, these results were based only on kids who had a history of inpatient treatment. Those with a history of only outpatient treatment were not included. It is possible that the observed link between parental psychiatric history and autism applies only, or mostly, to the most severe cases of autism requiring hospitalization.

One last comment: It's important to note that the rate of psychiatric conditions among even children with autism were very low. For example, schizophrenia was observed among 0.6% of the mothers of children with autism (compared to 0.2% of the typically developing mothers). 99.4% of the children with autism did not have mothers with schizophrenia. Therefore, the data only suggest that there may be a familial/genetic predisposition that is related to autism among very small subset of children with autism.

Autism and Inhibition of Return - A note about sample size

A review of: Rinehart, N.J., Bradshaw, J.L., Moss, S.A., Brereton, A.V., Tonge, B.J. (2008). Brief report: Inhibition of return in young people with autism and Asperger's disorder. Autism, 12(3), 249-260. DOI: 10.1177/1362361307088754

The authors designed an interesting experiment based on Minshew’s Complex Information Processing theory of autism, which seeks to understand the neuropsychological patterns of strengths and weaknesses in Autism as the foundations for the specific deficits in social cognition observed in Autism.

Side Note: Please note that the ‘Neuropsychological’ is usually misinterpreted, even by trained researchers and clinicians, as referring to physiological, as in ‘biological psychology’. Instead, neuropsychological refers in general to neurocognitive functioning – that is, cognitive and motor domains linked to brain processes. Thus, a test of neuropsychological functioning would include assessment of memory, attention, motor control, visual perception, auditory skills, general intelligence, language, etc.

Neuropsychological researchers have noted intact or superior abilities to detect unique patterns or items in visual search tasks in children with autism. This is inconsistent with the finding that these children also show difficulty with visual orientation and attentional set-shift (controlling the shifting of attention when needed from one set of items/tasks to others). Thus, how could children with autism have excellent item detection skills in light of their difficulty with attention and visual orientation? One possible explanation explored by the authors is that children with autism have a pronounced Inhibition of Return (IOR). IOR is a cognitive process that facilitates visual search by inhibiting searching on areas that have already been searched. For example, when looking for a letter ‘p’ on a poster full of letters ‘b’ and ‘d’, IOR allows you to search more effectively and those with a more pronounce IOR would be faster.

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bbdbddbbdbbdbbbdbbdbbdb
bdbbdbbdbbdbdddbdbbdbdb
dbbdpdbdbbdbbdbbdbbdbdb
bdbbdbbbdbbdddbdbbdbbdb
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In this study the authors compared 12 kids with high functioning autism, 12 kids with Asperger’s, and 12 typically developing kids, all matched for age (mean 10), sex, and IQ. Diagnoses were confirmed via ADI. The participants completed a series of tasks to measure IOR. The authors found no significant differences in IOR between those with ASD and typically developing kids. However, there was a trend at the (p = .052) level suggesting a more pronounced IOR among children with Asperger’s than the other two groups. This is worth noting because the authors ability to find statistically significant results is directly affected by the number of participants in each group. Thus, if these same results had been obtained with more participants, it is very likely that the difference observed would be statistically significant. This sample size related effect is more of a concern when the N of participants is very small. Thus, I will be more likely to ‘trust’ non-significant findings from a study using 1,000 participants than those from a study using only 20. One rule of thumb you can use when examining studies with small sample size (number of participants) is that statistically significant results are more "informative" than results not showing statistical significance. Why? Because the small sample size makes it more difficult to find statistically significant differences, so they require greater differences between the groups you are comparing. Thus, when you see a study using a small sample size that found a statistically significant difference, you can assume that the difference between the groups is there (assuming no other methodological problems). However, when the results show no statistical difference, this could mean that the difference between the groups does not exist, or that they needed a larger sample size.

Acetaminophen use and Autism.

A review of: Schultz, S.T., Klonoff-Cohen, H.S., Wingard, D.L., Akshoomoff, N.A., Macera, C.A., Ming Ji, . (2008). Acetaminophen (paracetamol) use, measles-mumps-rubella vaccination, and autistic disorder: The results of a parent survey. Autism, 12(3), 293-307. DOI: 10.1177/1362361307089518

A study in the latest issue of the journal Autism examined the possible role of acetaminophen use after MMR vaccine and autism. The authors provided an excellent review of the MMR vaccine-autism research, which indicates that although some clinical studies have found a link, most epidemiological studies have failed to find an association between MMR and autism. The authors noted that acetaminophen is commonly used to treat the adverse reaction of MMR vaccinations such a fever and rash. In addition, one study (Alberti et al, 1999) showed that some low functioning children with autism process acetaminophen differently. Thus, the authors proposed a innovative hypothesis: Does acetaminophen use after MMR vaccination increase the risk for Autism?

The authors recruited parents of typically developing children and children with autism via internet advertisement. The total sample included 83 parents completing the survey for children with autism and 80 parents completing the control survey. The surveys included a variety of questions about the child such as age, gender, what medications were used to prevent or treat reactions to the MMR vaccine, including aspirin, acetaminophen, or ibuprofen. The survey of parents of children with autism included additional questions about their children diagnosis such as whether a regression in development was observed.

The authors found that parents of children with autism reported:
- more adverse effects of MMR vaccine, including fever, diarrhea, irritability
- increased presence of concurrent illnesses with MMR vaccine
- more acetaminophen use after the MMR vaccine among children who had a reaction to the vaccine, children who had a regression in development, and those under 5.
- more acetaminophen use between 12 and 18 months of age
No association was found between ibuprofen use and autism.


A few caveats:
The finding that parents of children with autism reported more adverse effects of MMR vaccine or more concurrent illnesses with MMR vaccine is not overly informative. Note that these results were based on parental reports via internet with no possibility of verification of accuracy of such reports. So it is completely plausible to argue that given the extended media coverage of the vaccine-autism link, some parents of children with autism are more attuned to their children histories after vaccination and thus are more likely to remember or report complications. What is informative and actually interesting is that there was a significant difference in reports of acetaminophen use as compared to ibuprofen use. This difference can not easily be explained on the basis of some report bias. The problem is that acetaminophen use was reported much more frequently than ibuprofen use by all parents. So it could be argued that since parents of children with autism were more likely to report complications (even if just a by-product of recall bias), the use of acetaminophen will also appear to be different between the two groups.

Perception of voice gender in high functioning autism

A review of: Groen, W.B., Orsouw, L., Zwiers, M., Swinkels, S., Gaag, R.J., Buitelaar, J.K. (2008). Gender in Voice Perception in Autism. Journal of Autism and Developmental Disorders DOI: 10.1007/s10803-008-0572-8

Social perception using non-verbal means, such as recognition of the social information embedded into facial expressions, voices, and gestures, play a key role in social communication. Unlike typically developing kids, babies that are later diagnosed with autism do not show a preference for their mother’s voice as apposed to other voice sound. The authors of this study reviewed this and other evidence of atypical sound processing in autism, specially the finding that people with high functioning autism have an atypical cortical processing of voices when compared to typically developing kids. Based on these findings, the authors wanted to explore if theses differences in sound processing result in impaired ability to recognize the gender of a speaker base solely on voice perception.

The study included 20 adolescents with high functioning autism and 20 typically developing adolescents who were matched for IQ, gender, and age. Diagnoses were based on DSM-IV criteria and confirmed via ADI. The participants were presented voice fragments via headphones and were instructed to determine whether the voice was of a male or a female. The authors used a specialized software to morph the gender of the voices and thus present fragments that slowly changed from stereotypically masculine to stereotypically feminine.

The authors did not find any group differences in the accuracy for identifying the correct gender. Typically developing kids and those with high functioning autism were as accurate when identifying the gender of voice fragments. However, significant differences were observed in the speed of responding but only for the originally male morphed voices (male to female morph).

Please note however, that the differences in response time were not simple a 'mean' difference with those with HFA responding slower than typically developing kids. Instead, typically developing kids had a linear increase in response time as the voices were morphed. For example, they responded much faster when the voice was not morphed (original male voice presented as male voice) but gradually increased their response time as the voices were morphed, so that the slowest response time was when the voice was completely morphed (original male voice presented as a female voice). However, for those with HFA the effect was not linear. They responded fast when the voice was not morphed, slowed as the voice began to get morphed, but then became fast again when the voice was completely morphed.

The authors conclude that children with high functioning autism are not impaired in the perception of voice gender, but instead use a different perceptual approach resulting in different response times.

Mercury Exposure and Autism: Should you check for nearby power plants?

...But this study is compelling in showing an association between mercury exposure and autism rates, and scientists can not just ignore it under the basis of its imperfect design and inability to make causal links – if that is the case, then only carefully controlled laboratory studies, with poor external validity, should be published and accepted as contributors to our greater scientific knowledge.

A review of: PALMER, R., BLANCHARD, S., WOOD, R. (2008). Proximity to point sources of environmental mercury release as a predictor of autism prevalence. Health & Place DOI: 10.1016/j.healthplace.2008.02.001

This fascinating, yet bound to be controversial, study hit the news yesterday as it was made available (pre-publication) by the Journal Health & Place. The study is simple, straightforward, elegant, with some powerful findings. In fact, the findings are somewhat daunting given the simplicity of the design. The researchers reviewed the amount of mercury release reported by industrial facilities and power plants in the State of Texas in 1997 from data provided by US Environmental Protection Agency Toxics Release Inventory. They compared these data against autism rates in 1997 and 2002 as measured by schools' autism classifications provided by the Texas Education Agency. Using a specialized geographical analysis system, the authors were able to locate each source of mercury and calculate the distance between each mercury source and each school. The results:

Industrial release of mercury and distance to industrial sources independently predicted increased rates of autism. The association with industrial release of mercury was not linear, instead the statistical model fit suggested an accelerated risk. This association remained statistically significant after controlling for specific variables such as SES, urbanicity, and race.

Power plant release of mercury and distance to power plant independently predicted increased rates of autism. In this case the association was linear (not accelerated). Again, this association remained statistically significant after controlling for other variables.

It is easy to dismiss these findings as inconsequential because they are ‘correlational’ in nature, or do not really prove anything. Researchers are too often guilty of selective acceptance of research: those studies that fit the consensus are accepted while those that don’t are dismissed for their methodological flaws – even though the studies we accept are equally flawed.

In the spirit of fairness I have to say that these findings are strong. Their methodology and analytical process are not any different from what is commonly seen in social science or epidemiology research. Is it perfect? Far from it. Is it useful or informative? Definitively! The data speak very clearly: In Texas, mercury release from industrial sources and power plants in 1997, and school proximity to these sources, are associated with rates of autism in 2002 as measured by school special education classifications.

Does this mean that mercury causes autism? Not at all. In the last sentence of the previous paragraph you can not replace the words are associated with with the word cause. There is a major difference. The data, albeit strong, have limitations. For example, the most obvious (to me) alternative explanation is that mercury release and proximity to these sources is also associated with another mystery factor that is causing this apparent association and that in fact, mercury release has nothing to do with autism rates in 2002. Let’s hypothesize that these power plants and industrial sources also release another toxin – let’s call this toxin autisimic (this is a made up toxin). These sources release mercury and autisimic at the same rate, so for each pound of mercury released there is a pound of autisimic released. It is possible then that this autisimic toxin directly increases the risk for autism, and this could explain completely the strong (but now obviously inaccurate) association between mercury release and autism.

Does this study show that vaccines cause autism? Absolutely not. I know this question may sound ludicrous to some, but I pose it rhetorically because I am certain that some will make the wide leap and link these findings to the vaccine issue.

There are other problems and limitations with this study, such as how autism rates were calculated (using all children instead of only those born inor after 1997), whether the autism rates are truly climbing and not explained by other factors, whether there are other variables that could be explaining this relation, etc, etc --- and yes, this study does not prove or directly indicate that autism is caused by mercury exposure (click here for a much more critical review of this study). But this study is compelling in showing an association between mercury exposure and autism rates, and scientists can not just ignore it under the basis of its imperfect design and inability to make causal links – if that is the case, then only carefully controlled laboratory studies, with poor external validity, should be published and accepted as contributors to our greater scientific knowledge. This is study is far, far, from perfect, and many changes should have been requested prior to publication, but I can say the same of 90% of what is published today.