News and Notes about Scientific Research on Autism and other Developmental and Behavioral Disorders

Editor: Bill Ahearn, Ph.D., BCBA
Director of Research, The New England Center for Children

Recent genetics research on ASDs

Previous research suggests that autism may be the product of “genetically determined prenatal alterations in brain development” (Acosta & Pearl, 2003).  Neuroimaging work has found that children with autism aged 2 to 4 had larger brains with more cerebral and cerebellar white matter and more cerebral cortical grey matter than typically developing children of the same age (Courchesne et al., 2001).  However, Carper and colleagues (e.g., Carper et al., 2002) found that children with autism gain substantially less grey and white matter in the frontal lobes from early to late childhood relative to typically developing children.  Acosta and Pearl feel that current evidence points to abnormal timing and amount of brain growth and that growth in some areas may end prematurely.

A number of genetics researchers have been working towards identifying the genetic mechanisms that may underlie such abnormal brain development.  Autism spectrum disorders (ASD) have long been known to have genetic origins and approximately 10% of persons with an ASD have a known genetic anomaly such as Fragile X syndrome.  One recent large scale study found that persons with autism were much more likely to have a parent who had been diagnosed with schizophrenia or a mother diagnosed with either depression or a personality disorder than unaffected individuals (Daniels et al., 2008).  Such work helps to confirm suspicions as to the genetic origins of autism but other recent work has been looking to identify specific genetic mechanisms.

A study conducted by the Autism Consortium (headed by researchers at Children’s Hospital Boston) was published earlier this year in the New England Journal of Medicine.  It was found that the genes of 1% of persons with autism had a specific region on chromosome 16 in which there was either a duplication or deletion of a sequence of genes on a part of the chromosome (Weiss et al., 2008).  Genetic problems in chromosome 16 have been identified as a suspected mechanism that may underlie intellectual disabilities in general.  Finding this anomaly in persons with autism without impaired cognitive functioning will help to clarify the significance of this finding.

Another study has honed in on a specific gene region in chromosome 7, which is thought to be involved in language development.  Alarcon and colleagues (2008) identified a suspect gene on chromosome 7, CNTNAP2.  CNTNAP2 produces a protein involved in brain cell communication.  Mutations of this gene are speculated as potential sources for abnormal brain development.  The variant form of this gene was found significantly more often in persons with autism but this finding was gender specific.  That is, the scientists found that statistical evidence for the gene was strongest in families with boys diagnosed with an ASD relative to families with affected boys and girls, or in families with affected girls only. This genetic problem may be one reason associated with the higher incidence of ASDs in males.

Sebat and colleagues (2007) detected a higher likelihood of spontaneous mutations that were present in a child diagnosed with an ASD but the mutation was not present in either parent.  Among the children with autism who had the mutations, 12 out of 14 of them were the only affected members of their family.  The rate of such mutations was much lower in families with more than one affected member. The researchers propose that "two different genetic mechanisms contribute to risk: spontaneous mutation and inheritance, with the latter being more frequent in families that have multiple affected children." The two mutations detected in the typical control subjects were duplications, while the majority of those in people with autism were deletions. Relatively more females had the mutations, suggesting that the anomalies may contribute more equally across gender than other causes of autism.

Though there has been much learned from genetics research within the past few years, the genetic mechanisms responsible for the majority of cases of autism have not yet been identified.  One application of findings such as those reported above is the development of tests to screen for specific genetic presentations.  Groups, like our research partners at Children’s Hospital Boston, have been assessing screening tools based on these research findings.  The autism community has generally supported this type of research and the participation of many families is helping scientists better understand how autism develops.

The New England Center for Children (NECC)® continues to collaborate with Children’s Hospital, Boston to recruit participants for study of the genetic and environmental variables that may be involved in causing ASDs.  To date we have recruited a number of families and thank all of those who have participated.  Most families that are eligible to participate have already received a letter from NECC asking whether or not they would be interested in our referring their child to the Children’s genetics study.  If you would like more information about the study you may email the Research Department at research01852@necc.org.

 

Did the US government concede that vaccines cause autism?

There have been many reports in the popular media that the US government has conceded that vaccines cause autism in court.  This is incorrect.  In fact, one court case has already been dismissed because of the overwhelming evidence against this notion.  On February 8, 2008, Judge Stuart R. Berger of the Circuit Court for Baltimore City, Maryland, granted a motion for summary judgment in Blackwell v. Sigma Aldrich, Inc. et al. (No. 24-C-04-004829).  In this lawsuit, a family alleged that their child’s exposure to thimerosal-containing vaccines caused him to become autistic.  Expert witnesses for the plaintiffs included Dr. Mark Geier, Dr. Stephen Siebert, Dr. Elizabeth Mumper, Prof. Richard Deth, and Prof. Boyd Haley. The judge ruled their testimony failed to establish any link and that their opinions were contrary to expert opinions in the relevant scientific communities. 

However, there was a case decided in favor of the parents in vaccine court.  A prominent neurologist from Yale University, Steven Novella, has commented on this case and his comments form the basis of the following summary of this case (for a complete account of Dr. Novella’s analysis go to: http://www.theness.com/neurologicablog/?p=203#more-203). The child in the case appeared normal and healthy, except for chronic otitis media, until about 20 months of age at which time she had a series of vaccines according to the routine vaccination schedule. Two days later the child had a fever to 102.3, was lethargic, irritable, and would arch her back when she cried. The child then developed a rash. It was later determined that the child had: “encephalopathy progressed to persistent loss of previously acquired language, eye contact, and relatedness.” The child regressed and developed symptoms similar to those of autism spectrum disorder. However, the child does not have autism - she has a regressive neurological disorder that includes blood and muscle abnormalities not seen in autism, and any clinical resemblance to autism is not a reflection of a common cause.

It if often difficult or impossible to draw firm conclusions from a single case, so I [Dr. Novella] will lay out what I see as all the possible alternative hypotheses to explain this information.

1) One possibility is that the child was perfectly normal prior to the vaccines, which caused an encephalitis (inflammation of the brain), which then caused brain damage, including the later seizures. The metabolic disorder and mutation may be a red herring and have no bearing on the child’s clinical condition.

2) The mitochondrial disorder predisposed the child to have a reaction from the vaccines, resulting in encephalitis. The subsequent neurological regression was due to some combination of the vaccine-induced encephalitis and the underlying mitochondrial disorder.

3) The child’s mitochondrial mutation is the primary cause of her neurological regression, but that this regression was exacerbated by the vaccine-induced encephalitis (this seems to be the US government’s conclusion).

4) The child has a mitochondrial encephalopathy which is the sole cause of all of the child’s neurological signs and symptoms. The reaction to the vaccines may have played no role at all in the subsequent regression, and the child’s current neurological condition is exactly what it would have been had she never been vaccinated. It is even possible that the encephalitis was merely the first manifestation of the mitochondrial disorder and the timing after the vaccines was merely coincidental.

That lays out the spectrum of possibilities in this case. At this point in time we do not have sufficient scientific information to say definitively where along this spectrum the truth lies. The US government’s decision was based partly on this uncertainty - erring on the side of compensating the child and family. (end S. Novella commentary)

A definitive answer to whether thimerosal is linked to autism has to a large extent already been achieved.  If thimerosal caused autism, then the prevalence of autism should have dramatically declined when it was removed from vaccines.  Significant reductions started in 1998 with the process complete in 2001.  However, prevalence rates continue to rise to this day.  A firmer conclusion can be drawn by including evidence gathered in Denmark and Canada.  Following removal of thimerosal, prevalence rates have continued to rise there as well.  That said, it is unlikely that this evidence will ever be able to overcome the misplaced beliefs of antivaccinationists.  Society would do well to remember the true epidemics of smallpox, measles, polio, and other devastating childhood diseases.

Research at The New England Center

Editor’s note: Staff from NECC have recently published several articles in peer reviewed journals. I am presenting a few of those in this issue of the Research Newsletter.  A complete list of research publications can be found on NECC’s website at this address:
http://www.necc.org/research/publications.asp

The majority of research studies conducted at NECC focus on improving our skills in delivering effective instruction to children with autism and related disorders. The next two published articles are excellent examples of how some questions about the most effective procedures for teaching children have been answered through systematic research.  The first study was conducted in our residential services with the goal of answering whether students learn quicker with a trial-and-error teaching procedure (least-to-most prompts) relative to an approach that minimizes errors (most-to-least prompts). NECC clinicians have long operated on the notion that errorless learning is a best practice strategy. However, we have seen many children learn more rapidly with a trial-and-error approach.  The two studies reported here show that trial-and-error teaching can lead to quicker acquisition for some students but others may never learn with it and require an errorless approach.  We also demonstrated that a hybrid procedure (delayed cueing +most-to-least) can both minimize errors while fostering the emergence of independent skill performance.

Libby, M.E., Weiss, J.S., Bancroft, S., & Ahearn, W.H. (2008).  A comparison of most-to-least and least-to-most prompting on acquisition of solitary play skills. Behavior Analysis in Practice, 1, 37-43.

Two studies are presented in which common prompting procedures were evaluated while teaching children with autism to build Lego® play structures.  In the first study, most-to-least (MTL) and least-to-most (LTM) prompting were compared.  All participants learned to build the play structures when the teacher used MTL, which was associated with fewer errors than LTM.  Nonetheless, three participants learned more quickly with LTM. This finding suggests that MTL may prevent errors, but it sometimes slows learning. The second study compared LTM to MTL without and with a delay (MTLD). MTLD provided an opportunity for the child to independently initiate responding but still minimized the likelihood of errors. Results showed that acquisition was nearly as rapid when the teacher used MTLD as LTM but it produced fewer errors than LTM.  Best practice guidelines for choosing prompting procedures are proposed.
Descriptors:  autism, behavior chains, play skills, prompting.

Editor’s note: This second study, also conducted with children from the residential program at NECC, builds upon the growing body of evidence that video modeling can be an effective tool for teaching children complex skills.  Behavior analysts often break up a motor skill like tooth brushing into the many smaller skills of which the complete skill is comprised and then teach a student one skill at a time. This study shows that video modeling can lead to more rapid learning.  The authors taught two skills to the students and they provided the same instruction (least-to-most prompting) but also used video modeling for one skill. This study focused on motor skills but video modeling has also been found beneficial in teaching play and social skills and verbal communication.

Murzynski, N.T., & Bourret, J.C. (2007).  Combining video modeling and least-to-most prompting for establishing response chains. Behavioral Interventions, 22, 147-152.

Video modeling combined with least-to-most intrusive prompting was compared using a parallel-treatments design to least-to-most intrusive prompting alone in teaching daily-living skills in the form of response chains.  Two boys with the diagnosis of autism (ages 8 and 9) participated in the study.  The results showed that the participants acquired skills taught with video modeling plus least-to-most prompting in fewer trials and with fewer prompts than skills taught with least-to-most prompting alone.

Editor’s note: The next two abstracts also involve improving the skills of behavioral clinicians.  They are both technical articles and require a little explanation. The first study was conducted with students at NECC with severe problem behavior. In order for clinicians to make rapid decisions while assessing and treating problem behavior, behavior analysts will often have to take brief samples of behavior rather than continuously recording it.  This study follows some previous research conducted at NECC showing the situations in which the behavior analyst gets more or less reliable information from their sampling procedures.  In the previous study, it was shown that momentary time sampling was most accurate for capturing behavior with a varying duration such as stereotypy.  The present study extends this finding and also shows that behavior that is very brief in duration and discrete like self-injury and aggression, can be more accurate sampled using partial-interval recording.

Meany-Daboul, M.G., Roscoe, E.M., Bourret, J.C., & Ahearn, W.H. (2007).  A comparison of momentary time sampling and partial-interval recording procedures for evaluating functional relations.  Journal of Applied Behavior Analysis, 40, 501-514

In the current study, momentary time sampling (MTS) and partial-interval recording (PIR) were compared to continuous-duration recording of stereotypy and to the frequency of self-injury during a treatment analysis to determine whether the recording method affected data interpretation. Five previously conducted treatment analysis data sets were analyzed by creating separate graphic displays for each measurement method (duration or frequency, MTS, and PIR). An expert panel interview and structured criterion visual inspection were used to evaluate treatment effects across measurement methods. Results showed that treatment analysis interpretations based on both discontinuous recording methods often matched those based on frequency or duration recording; however, interpretations based on MTS were slightly more likely to match those based on duration and those based on PIR were slightly more likely to match those based on frequency.
DESCRIPTORS: measurement, momentary time sampling, partial-interval recording

Editor’s note: This last abstract is a paper that details a procedure for easily generating procedures for producing variable or random schedules of consequences.  Most service providers use schedules that are very predictable.  Oftentimes this produces undesirable side effects like long pausing by the student after receiving access to a reinforcer. This paper provides clinicians any easy tool for developing schedules that will more fluently support behavior and that may generate more responding by students with less reinforcement.

Bancroft, S.L., & Bourret, J.C. (in press).   Generating variable and random schedules of reinforcement using Microsoft Excel™ macros. Journal of Applied Behavior Analysis.

Variable reinforcement schedules are used to arrange the availability of reinforcement following varying response ratios or intervals of time.  Random reinforcement schedules are subtypes of variable reinforcement schedules that can be used to arrange the availability of reinforcement at a constant probability across number of responses or time.  Generating schedule values for variable and random reinforcement schedules can be difficult.  The present article describes the steps necessary to write macros in Microsoft ExcelTM that will generate variable-ratio, variable-interval, variable-time, random-ratio, random-interval, and random-time reinforcement schedule values. 
DESCRIPTORS:  Schedules of Reinforcement, Variable Interval, Random Interval, Variable Time, Random Time, Variable Ratio, Random Ratio, Schedule Generation

Web Resources

• For information about The New England Center for Children or to access and electronic version of this or previous NECC Research Newsletters, visit our Web site www.necc.org.
• For information about autism, visit the National Library of Medicine’s autism site www.nlm.nih.gov/medlineplus/autism.html.
• For information about applied behavior analysis in the treatment for autism visit www.behavior.org.
• For information on health issues in general visit the World Health Organization www.who.int.
• For professionally-screened information on health care (including some treatments for autism and other developmental disabilities), visit www.quackwatch.com.
• For information on the Berkshire Association for Behavior Analysis and Therapy, visit http://www.babat.org.
• For information on the Association for Behavior Analysis, visit http://www.abainternational.org/

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