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.
Continue reading ‘De novo mutations and Autism redux’
Tag Archive for 'Research'
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.
Sphere: Related ContentWhen 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.
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
Sphere: Related ContentDennis Reid, a renowned researcher and clinician who for more than 35 years has worked with individuals who have Autism, will speak on 22 September 2011 on “Evidence-Based Strategies for Promoting Enjoyment among People with Autism” in Charlottesville (VA, US). The talk by Mr. Reid, which is free and open to the public (but registration is required), is part of the Virginia Institute of Autism (VIA) Autism Speaker Series and is sponsored by VIA and the University of Virginia Children’s Hospital. It is scheduled for 5:30-6:30 at St. Anne’s-Belfield Greenway Rise Campus, Randolph Hall Auditorium. To register, go to VIA’s Web site viaschool.org or call (434) 923-8252.
For those who are unfamiliar with Mr. Reid’s research, he has an extensive record of work in behavior analysis, having published repeatedly in the Journal of Applied Behavior Analysis. He’s based at the Carolina Behavior Analysis and Support Center in Mogantown (NC, US) which, oddly, doesn’t seem to have a Web site.
Sphere: Related ContentIn Pediatrics Professor Sally Ozonoff and her colleagues of the Baby Siblings Research Consortium have reported data indicating a substantially higher risk for Autism among siblings than had been previously found. Based on data from studies in the 1980s, estimates of the risk of Autism in a child given that an older sibling had Autism were in the range of 3 to 5%, the Consortium found that the risk may be as great as four times higher than that, perhaps as high as 20%.
The researchers in the Consortium used very careful methods in which they found 664 later-born, biological siblings of a child with Autism when that younger sibling was, on average, about 8 months old. They followed the development of the siblings and assessed whether they had the symptoms of Autism when they were 36 months old. They found almost 19% had scores above the cut-off for Autism. The risk for Autism was even greater for boys and when more than one older sibling had Autism.
Continue reading ‘Little sibs of children with ASD have greater risk of Autism’
Do you want to know more about evidence-based interventions for Autism? Are you weary of wading through a lot of over-hyped-and-not-well-tested methods hoping to find one gem? Do you come back to EBD Blog because you pine for trustworthy news about Autism?
There is an alternative, another source: The Association for Science in Autism Treatment has a regular newsletter and a new one is about to be released. If readers hustle their bustles, they can register in time to receive the next issue which includes (according to a mailer I received)
- A feature article in which Dr. Thomas Zane discusses the adoption of Fad Treatments in Autism.
- Four research article summaries (ranging from treatment comparisons to prevalence of adults with autism).
- Spotlight on a new organization Advancing Futures for Adults with Autism.
- Two Clinical Corners (Food Selectivity and Help with the Dentist).
- Consumer Corner (Review of Transition Resources for Adolescents and Adults with Autism).
- An in-depth group interview about fostering positive portrayals of science-based treatment in the media.
…and for the rest, you’re just going to have to read to find out!
Here’s a link to register for the newsletter: http://www.asatonline.org/signup. I encourage folks to do.
And, if you ever forget how to find ASAT, you don’t have to poke around looking for this message. Just check over there in the siderail. You’ll find it listed in the “Web Resources.”
Sphere: Related ContentIn an accompanying PDF I have listed studies that are currently seeking children (both female and male) with Emotional of Behavioral Disorders (especially autism spectrum disorders) as participants (some include adults, as well) that are registered with ClinicalTrials.gov, a service of the US National Institutes of Health (NIH). The studies have diverse purposes: They may be observing different events (whether overt behavior or neurochemical activity) or they may be testing different therapies (ranging from behavioral to medical methods). Many are sponsored at least in part by the NIH, but some have funding from universities or even private industries. Because of its affiliation with NIH, ClincialTrials.gov is more likely to represent medically oriented studies and studies that use rigorous scientific methods (i.e., randomized clinical trials or RCTs), but this is not exclusively the case. Readers should examine the studies carefully.
The list is not exhaustive (I used “autism” in the search, so there are many more studies that could be located by using other terms), and I’ve provided only some of the data about each study in the table, but you can learn a fair bit about individual studies. For example, one can learn about study number NCT00198107 that is entitled “Evaluating the Effectiveness of Aripiprazole and D-Cycloserine to Treat Symptoms Associated With Autism.” It focuses on individuals with Autistic Disorders and examines an intervention (in this case, comparing drugs called Aripiprazole D-cycloserine to placebo in a randomized design with double-blind (Subject, Caregiver, Investigator, Outcomes Assessor) | Primary Purpose: procedures. The study began 1-Sep-05 and will end 1-Sep-11 (making it odd that it is still listed as open, no?).
To locate additional information about a particular study, copy the NCT ID number, go to ClinicalTrials.gov, and enter that number into the search box. Download the PDF here (10 pages).
Sphere: Related ContentIn the Journal of Behavior Therapy and Experimental Psychiatry, Joanna Kowalik and colleagues reported that their review of studies on the use of cognitivie behavioral therapy for treating posttraumatic stress disorder (PTSD) revealed that cog-mod appears effective in changing raters’ responses on some of the widely used scales of the Child Behavior Checklist. However, the results of their literature review are not as powerful as one might hope, given the small number of studies and substantial variability in the studies themselves.
Abstract
Background and objectives There is no clear gold standard treatment for childhood posttraumatic stress disorder (PTSD). An annotated bibliography and meta-analysis were used to examine the efficacy of cognitive behavioral therapy (CBT) in the treatment of pediatric PTSD as measured by outcome data from the Child Behavior Checklist (CBCL).
Method A literature search produced 21 studies; of these, 10 utilized the CBCL but only eight were both 1) randomized; and 2) reported pre- and post-intervention scores.
Results The annotated bibliography revealed efficacy in general of CBT for pediatric PTSD. Using four indices of the CBCL, the meta-analysis identified statistically significant effect sizes for three of the four scales: Total Problems (TP; ?.327; p = .003), Internalizing (INT; ?.314; p = .001), and Externalizing (EXT; ?.192; p = .040). The results for TP and INT were reliable as indicated by the fail-safe N and rank correlation tests. The effect size for the Total Competence (TCOMP; ?.054; p = .620) index did not reach statistical significance.
Limitations Limitations included methodological inconsistencies across studies and lack of a randomized control group design, yielding few studies for meta-analysis.
Conclusions The efficacy of CBT in the treatment of pediatric PTSD was supported by the annotated bibliography and meta-analysis, contributing to best practices data. CBT addressed internalizing signs and symptoms (as measured by the CBCL) such as anxiety and depression more robustly than it did externalizing symptoms such as aggression and rule-breaking behavior, consistent with its purpose as a therapeutic intervention.
Because they are integrating so few studies it is very difficult to have a sensitive meta-analysis in this case. However, that Professor Kowalik and her collaborators found differences at all is encouraging. I hope they’ll continue to follow this literature. Also, I hope researchers will be using other measures of outcomes and that those other measures will be examined in future integrative literature reviews, too.
Kowalik, J., Weller, J., Venter, J., & Drachman, D. (2011). Cognitive behavioral therapy for the treatment of pediatric posttraumatic stress disorder: A review and meta-analysis. Journal of Behavior Therapy and Experimental Psychiatry, 42, 405-413. doi:10.1016/j.jbtep.2011.02.002
Sphere: Related ContentShanthi Krishnaswami and colleagues examined the research about the effects of using secretin as a theraputic agent for the treatment of Autism. They found that there were none of the seven randomized controlled trials showed beneficial effects and, therefore, concluded that secretin does not merit consideration as a therapy. Their finding, which employs rigorous methods, is consistent with earlier analyses that examined more preliminary research and which I have reported previously (as far back as the 1990s).
Sphere: Related ContentA Systematic Review of Secretin for Children With Autism Spectrum Disorders
by
Shanthi Krishnaswami, Melissa L. McPheeters and Jeremy Veenstra-VanderWeeleCONTEXT: As many as 1 in every 110 children in the United States has an autism spectrum disorder (ASD). Secretin is 1 of many medical treatments studied for treating the symptoms of ASDs, but there is currently no consensus regarding which interventions are most effective.
OBJECTIVE: To systematically review evidence regarding the use of secretin in children with ASDs who are aged 12 years and younger.
METHODS: We searched the Medline, PsycINFO, and ERIC (Education Resources Information Center) databases from 2000 to May 2010 and reference lists of included articles. Two reviewers independently assessed each study against predetermined inclusion/exclusion criteria. Two reviewers independently extracted data regarding participant and intervention characteristics, assessment techniques, and outcomes and assigned overall quality and strength-of-evidence ratings on the basis of predetermined criteria.
RESULTS: Evidence from 7 randomized controlled trials supports a lack of effectiveness of secretin for the treatment of ASD symptoms including language and communication impairment, symptom severity, and cognitive and social skill deficits. No studies have resulted in significantly greater improvements in measures of language, cognition, or autistic symptoms when compared with placebo; study authors who reported improvement over time did so equally for both the intervention and placebo groups.
CONCLUSIONS: Secretin has been studied extensively in multiple randomized controlled trials, and there is clear evidence that it lacks benefit. The studies of secretin included in this review uniformly point to a lack of significant impact of secretin in the treatment of ASD symptoms. Given the high strength of evidence for a lack of effectiveness, secretin as a treatment approach for ASDs warrants no further study.
Krishnaswami, S., McPHeeters, M. L., & Veenstra-VanderWeele, J. (2011). A systematic review of secretin for children with autism spectrum disorders. Pediatrics, 127, 1322-1325. DOI 10.1542/peds.2011-0428
For those readers interested in Autism who do not already subscribe to the newsletter of the Association for Science in Autism (ASAT), I have a nourishing treat: The latest issue of Science in Autism Treatment (SIAT) is now available. You can learn about ASAT and SIAT by going to the ASAT homepage and scouting about the many valuable resources there, including learning about and subscribing to the SIAT newsletter. Subscribe and you won’t have to depend on my flaky reminder system to let you know when one arrives in my mailbox!
Sphere: Related Content
These are the lead researchers in the Conduct Problems Prevention Research Group with their current universities (over the years, some have changed affiliations):
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The Conduct Problems Prevention Research Group, a team of composed of seven of the most eminent US scholars studying the development of childhood behavior disorders, published another in its series of papers tracking the outcomes of the children it has been following in a long-term study about preventing acting out disorders. In this longer-term follow-up analysis, the team found that the effects were still present for the children who showed the most risk of having behavior disorders in the first place.
This project and these folks are the big time. The work has been conducted very carefully and cannot be represented as an example of over-hyped findings.
Continue reading ‘Follow up of Fast Track’
The Council for Children with Behavioral Disorders (CCBD) is hosting a meeting at the Sheraton Norfolk Waterside Hotel in Norfolk (VA, US) and the registration deadline is tomorrow, 3 February 2011. CCBD has reduced the fees and there are spcial discounted rates for teams of three or more attendees.
Continue reading ‘CCBD conference 2011′
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