Tag Archive for 'Research'

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Can a child recover from Autism?

Yesterday I wrote about how, when people consider individual cases, the possibility of improvement for children with Autism might make otherwise inert therapies appear to be beneficial. In yesterday’s post I referred to research by Molly Helt and colleagues (2008) about recovery among individuals with Autism, and I hinted about an important recent study by Deborah Fein and her colleagues (2013) related to that phenomenon. Today I discuss that second study.

The more recent study is just another among many by Professor Fein, who was a principal author on the Helt et al. (2008) study, and who has been doing exemplary work about Autism and Autism Spectrum Disorders (ASD) for many years. In this one she provides new data about “recovery,” a word they rarely use in the course of their article.

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Autism, recovery, CAM, placebo, and research

Thought experiment: Suppose that scientists want to compare a new therapy for children with Autism. They’ll need to compare the New Therapy to a control condition and evaluate it over time using multiple different outcome measures. I’m going to describe this because I want to talk about the effects of “recovery” in Autism in the control group, the perception of the effectiveness of complimentary and alternative therapies, and the placebo effect.

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Briefer, accurate diagnosis of Autism is possible

Using machine-learning techniques, Professor Dennis Wall and colleagues were able to achieve highly accurate classification of children with Autism that only required a small selection of items from the Autism Diagnostic Observation Schedule-Generic (ADOS). The ADOS, a semi-structured and standardized assessment used with children suspected of having Autism, has four 30- to 60-minute parts where children are observed for social interaction, communication, play, and imaginative use of materials; it is very widely used in diagnosis of Autism, Pervasive Developmental Disorder Not Otherwise Specified (PDDNOS), and non-spectrum disorders. As they reported in Translational Psychiatry, Professor Wall’s team was able to determine that 8 of the 29 items in Module 1 of the ADOS were sufficient to classify autism with 100% accuracy.
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Swedish population study puts prevalence of Autism at 1.15%

By studying the entire population of children in Stockholm (SW) during the time period 2001-2007, Selma Idring and colleagues at the Department of Public Health Sciences of the Karolinska Institute in Stockholm were able to ascertain that the prevalence of Autism for the year 2007 was about 11.5 per 1000 or 1.15%. In addition, they found that about 43% of those with Autism also had co-morbid intellectual disabilities.

Reporting in PLoS ONE, Professor Idring’s research group reported the results of their study that examined records for virtually all of the children (n=444,154) in a geographic area (for example, they tracked 99.8% of all preschool children) and matched those against multiple national and regional registers that showed which children had received services for Autism disorders (provided free of charge in Stockholm). They validated their case ascertainment with a subsample, too.

graph showing change in prevelance of autism by age and by comorbid ID

In addition to reporting the overall prevalence and the differences in comorbidity, the researchers reported variations in prevalence by gender and age group. The figure at the right shows one of those relationships. For details, please see the full article, available online for free. It’s linked in the following reference.

These data fit well with other carefully conducted studies about prevalence, but they are not as high as the widely discussed estimates that are based on softer ascertainment methods (e.g., studies that ask parents if anyone has discussed “autism” in relation to their child). Different methods will lead to different estimates. Compare the Idring group’s results and methods, for example, with the 2012 US Centers for Disease Control ADDM report (Community Report From the Autism and Developmental Disabilities Monitoring (ADDM) Network).

Idring, S., Rai, D., Dal, H., Dalman, C., Sturm, H., Zander, E., … & Magnnusson, C. (2012) Autism spectrum disorders in the Stockholm Youth Cohort: Design, prevalence and validity. PLoS ONE 7(7): e41280. doi:10.1371/journal.pone.0041280

Parent questionnaire picks up ASD at age one

According to a report published 10 July 2012 in Autism: The International Journal of Research & Practice by Lauren Turner-Brown and her colleagues of the University of North Carolina, their First Year Inventory (FYI) completed by parents when their children were only one year old correctly identified nine children who were later found to have Autism Spectrum Disorders.

Initially almost 1200 parents completed the FYI—a 63-item questionnaire that only requires about 10 minutes to fill out—when their children were 12 months old and agreed to participate in later research; at the time they completed the FYI the researchers had no scales to indicate whether scores indicated risk. At follow-up within 6 months of the the children’s third birthday, almost 700 then completed additional assessments—Social Responsiveness Scale–Preschool Version and the Developmental Concerns Questionnaire. Using these data (which they scored liberally so they wouldn’t miss possible cases), the researchers identified children at risk for developmental disorders.

They invited families of those at risk (as well as a few not-at-risk children so that the psychologists, who were kept naive about the purposes of the assessments, doing the assessments would have a few “ringers” in the group) to visit the research site for additional assessments. Assessments included the Mullen Scales of Early Learning and the Autism Diagnostic Observation Schedule; parents completed a clinical interview, the Vineland Scales of Adaptive Behavior (2nd Edition), and an autism spectrum diagnostic checklist of symptoms according to Diagnostic and Statistical Manual of Mental Disorders–Fourth Edition.

Using these data, the researchers were able to identify the the nine cases of ASD (6 with Autism, 3 with PDDNOS). (Of course, some had been diagnosed in the community.) In addition, they found that over 40 children apparently had been diagnosed or treated for non-ASD developmental problems, and over 80 more children were in a group they called “Developmental Concerns” meaning that “that parents reported some concern or that a professional had noted some concern about the child” (p. 9). In total, that is roughly 18% of their 700 participating children.

“These results indicate that an overwhelming majority of children who screen positive on the FYI indeed experience some delay in development by age three that may warrant early intervention,” Grace Baranek, senior developer of the FYI, said.

Now that Professor Turner-Brown and her colleagues have been able to follow this sample of children into early childhood, they can see how their instrument predicts developmental problems, and they will be able to begin using it more practically. Additional payoff will come as they are able to follow the children into the school years.

Although this research team is focusing on Autism and ASD, it may be that their larger contribution will be the benefits of screening for a wide spectrum of disorders. Early detection and intervention is likely to be beneficial for problems beyond ASD!

Turner-Brown, L. M., Baranek, G. T., Reznick, J. S., Watson, L. R., & Crais, E. R. (2012). The First Year Inventory: A longitudinal follow-up of 12-month-old to 3-year-old children. Autism, 16. Published online before print July 10, 2012. doi: 10.1177/1362361312439633

The UNC Med School’s press release provided the quotes I’ve used here: Questionnaire completed by parents may help identify 1-year-olds at risk for autism. The FYI questionnaire was developed by the Program for Early Autism Research, Leadership & Service (PEARLS) team. One can learn more about the FYI from the PEARLS Web site.

De novo mutations and Autism redux

In articles published online by Nature, Professors Stephan Sanders and colleagues and Brian J. O’Roak his colleagues reported additional evidence that rare mutations contribute to risk for Autism. By analyzing genetic material from parents who had children with Autism, the researchers were able to focus on differences in specific genes, what changed from one generation to the next. One team, working in the research lab of Professor Matthew State at Yale University, found strikingly unusual matches for a specific mutation at SCN2A. The other team, under the direction of Professor Evan Eichler at the University of Washington, found several candidates (including SCN1A) and a strong (4 to 1) relationship for older fathers.
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First Step supported by WWC

The US What Works Clearinghouse (WWC) reviewed research about First Step to Success, an early intervention program for K-3 children who are at risk of developing antisocial behavior, and identified it as having positive effects on ratings of student behavior and potentially positive effects on ratings of emotions, social skills, and academic outcomes. The WWC based its review on two studies by the developers of First Step, Hill Walker and colleagues—alert readers of EBD Blog will recognize one of them (see “First Step Takes Off“).

What Works—which some folks have taken to calling “what doesn’t work,” because they say it rarely identifies practices that are effective—gave the research undergirding First Step a strong review:

The WWC review of interventions for Children Classified as Having an Emotional Disturbance addresses student outcomes in seven domains: external behavior, emotional/internal behavior, social outcomes, reading achievement/ literacy, math achievement, school attendance, and other academic performance. The two studies that contribute to the effectiveness rating in this report cover five domains: external behavior, emotional/internal behavior, social outcomes, reading achievement/literacy, and other academic performance. The findings below present the authors’ estimates and WWC-calculated estimates of the size and statistical significance of the effects of First Step to Success on children classified as having an emotional disturbance….

Two studies reported findings in the external behavior domain.

Walker et al. (1998) found, and the WWC confirmed, four positive and statistically significant differences between treatment and comparison groups on academic engaged time, the Child Behavior Checklist–Teacher Report Forms (CBCL-TRF) Aggression Subscale, the Early Screening Project (ESP) Adaptive Behavior Subscale, and the ESP Maladaptive Behavior Subscale.

Walker et al. (2009) found, and the WWC confirmed, four positive and statistically significant differences between treatment and comparison groups on academic engaged time, the Social Skills Rating System (SSRS) Problem Behavior Subscale for Parents, the SSRS Problem Behavior Subscale for Teachers, and the SSBD Maladaptive Behavior Index. Although the overall design of the Walker et al. (2009) study meets evidence standards, there was high attrition on one outcome: the SSRS Problem Behavior Subscale for Parents outcome. The authors established equivalence for the analytic sample for this outcome; thus, this finding meets evidence standards with reservations.

The mean effect size from the four outcomes in Walker et al. (1998) and the mean effect size from the four out- comes in Walker et al. (2009) were both statistically significant. Thus, for the external behavior domain, two studies with strong designs showed statistically significant positive effects. This results in an intervention rating of positive effects for the domain, with a small extent of evidence.

Walker, H. M., Kavanagh, K., Stiller, B., Golly, A., Severson, H., & Feil, E. (1998). First Step to Success. An early intervention approach for preventing school antisocial behavior. Journal of Emotional and Behavioral Disorders, 6, 66–80.

Walker, H. M., Seeley, J. R., Small, J., Severson, H. H, Graham, B. A., Feil, E. G., . . . Forness, S. R. (2009). A randomized controlled trial of the First Step to Success early intervention: Demonstration of program efficacy outcomes in a diverse, urban school district. Journal of Emotional and Behavioral Disorders, 17, 197–212.

Infant eye gaze predicts ASD

When they look at models who are looking toward them versus away from them, the variation in brain activity in infants who later develop Autism Spectrum Disorders (ASD) is different than that of their peers who do not develop ASD, according to Mayada Elsabbagh and colleagues in a study published in Current Biology. Infants who do not later develop ASD apparently are already tuning into whether human-like models are looking at them, but those who develop ASDs are doing so to a lesser degree.

Professor Elsabbagh studied 104 children, about half of whom were classified as at risk for ASD because they had an older sibling who had an ASD. They initially tested them at six months of age and, later, broke them into four groups: (a) A control group, (b) children who were at-risk but had not developed ASD by age three, (c) children who were at-risk and developed ASD symptoms by age three, and (d) children who were at-risk and developed ASD early.

detail from Elsbbagh et al. graph

At 6 to 10 months of age, the brain activity of the infants in the control group and the at-risk-without-ASD group already showed sensitivity to whether a model was looking toward or away from the children. However, the brain activity of infants who later developed ASD showed less sensitivity. The accompanying graph illustrates the results on one of their measures. (Note that the measure shown in the figure here is not the one of greatest interest to the researchers.)

Even though it is difficult to find overt behavioral markers of ASD during the first year of life, these findings support the idea that there are brain function measures that can discriminate between groups of infants at risk for ASD. It’s important to note that these data are at the group level. They can’t be taken at the individual level, so the data are not ready for diagnostic purposes.

The researchers included a group from the collaborative network supporting research with infants at risk for autism in the UK, the British Autism Study of Infant Siblings (BASIS). This group and comparable groups elsewhere are wonderful partners for research and deserve great credit for the collaboration in efforts such as this.

Here is the abstract from the article:

Autism spectrum disorders (henceforth autism) are diagnosed in around 1% of the population [1]. Familial liability confers risk for a broad spectrum of difficulties including the broader autism phenotype (BAP) [ [2] and [3]]. There are currently no reliable predictors of autism in infancy, but characteristic behaviors emerge during the second year, enabling diagnosis after this age [ [4] and [5]]. Because indicators of brain functioning may be sensitive predictors, and atypical eye contact is characteristic of the syndrome [ [6], [7], [8] and [9]] and the BAP [ [10] and [11]], we examined whether neural sensitivity to eye gaze during infancy is associated with later autism outcomes [ [12] and [13]]. We undertook a prospective longitudinal study of infants with and without familial risk for autism. At 6–10 months, we recorded infants’ event-related potentials (ERPs) in response to viewing faces with eye gaze directed toward versus away from the infant [14]. Longitudinal analyses showed that characteristics of ERP components evoked in response to dynamic eye gaze shifts during infancy were associated with autism diagnosed at 36 months. ERP responses to eye gaze may help characterize developmental processes that lead to later emerging autism. Findings also elucidate the mechanisms driving the development of the social brain in infancy.

Elsabbagh, M., Mercure1, E., Hudry, K., Chandler, S., Pasco, G., Charman, T.,…the BASIS Team. (2012). Infant neural sensitivity to dynamic eye gaze is associated with later emerging autism. Current Biology. Advance online publication. doi:10.1016/j.cub.2011.12.056