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Summary of Advances Cover 2017

Summary of Advances

In Autism Spectrum Disorder Research


Question 4: Which Treatments and Interventions Will Help?

Adaptive behavior in autism: minimal clinically important differences on the Vineland-II
Chatham CH, Taylor KI, Charman T, Liogier D’ardhuy X, Eule E, Fedele A, Hardan AY, Loth E, Murtagh L, Del Valle Rubido M, San Jose Caceres A, Sevigny J, Sikich L, Snyder L, Tillmann JE, Ventola PE, Walton- Bowen KL, Wang PP, Willgoss T, Bolognani F. Autism Res.. 2017 Sep 21. [Epub ahead of print] [PMID: 28941213]

ASD is associated with impairments in adaptive behaviors, including social, communication, and independent living skills. Several assessment instruments exist for measuring these impairments, including the Vineland Adaptive Behavior Scales, Second Edition (Vineland-II). These tools are used to assess the extent of social and behavioral impairments such as communication, daily living skills, socialization, and motor skills. They can also be used to track progress over time, including during and after an intervention. A change in the Vineland-II score may indicate a meaningful benefit in daily life, but other factors such as age or cognitive ability may affect the effectiveness of an intervention. More importantly, it is not yet clear what amount of change in assessment score on the Vineland-II is clinically significant. Therefore, the researchers in this study sought to determine the smallest score change on the Vineland-II that could be considered clinically meaningful (known as the Minimal Clinically Important Difference, or MCID) and investigate if MCID could be dependent on other clinical factors.

The researchers used existing datasets to compare data from over 9,000 individuals with ASD who had been assessed with the Vineland-II. They used two types of analysis to determine the Vineland-II MCID: 1) a distribution-based MCID estimate, to calculate the amount of change not due to normal variation and 2) an anchor-based MCID estimate, to “anchor” an amount of change to other assessment scales in which clinically meaningfulness has already been established.

Subject data was grouped based on age (0 to less than 13 years, 13 to less than 18 years, and 18+ years) and by IQ (IQ less than 70, IQ 70 or greater). Across all groups, the MCID estimated score change by the anchor-based method ranged from 2.44 to 3.76, and by the distribution-based estimate ranged from 2.01 to 3.20. Lower estimates were seen among younger populations and those with lower IQ scores. The researchers also compared differences in MCID values based on sex and saw no significant difference between males and females. Overall, these results indicate that a score change on the Vineland-II between 2.00 and 3.75 points reflects clinically meaningful change for individuals with ASD across all age groups, IQ levels, and sexes. The results of this study are important because they establish a score change value that will help clinicians better understand the effectiveness of a treatment or intervention.

A randomized, placebo-controlled trial of metformin for the treatment of overweight induced by antipsychotic medication in young people with autism spectrum disorder: open-label extension
Handen BL, Anagnostou E, Aman MG, Sanders KB, Chan J, Hollway JA, Brian J, Arnold LE, Capano L, Williams C, Hellings JA, Butter E, Mankad D, Tumuluru R, Kettel J, Newsom CR, Peleg N, Odrobina D, McAuliffe-Bellin S, Marler S, Wong T, Wagner A, Hadjiyannakis S, Macklin EA, Veenstra-VanderWeele J. J Am Acad Child Adolesc Psychiatry.. 2017 Oct;56(10):849-856.e6. [PMID: 28942807]

Children with ASD who display disruptive behaviors are often treated with atypical antipsychotic medications, for which a common side effect is significant weight gain. Because atypical antipsychotic medications can be highly effective at decreasing disruptive behaviors, clinicians sometimes suggest that continuing the medication while treating the negative side effects is preferable to discontinuing the medication altogether.

Metformin is a drug that can treat weight gain through increased insulin sensitivity, meaning the body will absorb and produce less glucose (sugar). In this study, researchers tested the effectiveness of metformin for managing weight gain in children who take antipsychotics for ASD-related disruptive behaviors. In the first phase of the study, children with ASD aged 6 to 17 years-old who reported weight gain while taking antipsychotic drugs were given either metformin or a placebo for 16 weeks. In the second phase, the children who were previously given metformin in the first phase continued taking it for another 16 weeks (M-M group), and the children who were previously given a placebo began taking metformin for 16 weeks (P-M group). The researchers wanted to know if 1) children in the M-M group were able to maintain their weight loss from the initial phase of the trial, and 2) children in the P-M group would begin to lose weight when they switched from the placebo to metformin. The researchers used weight and body mass index (BMI) to measure the effectiveness of metformin.

In the first phase of the trial, the average weight and BMI for the children in the M-M group was significantly reduced, while that of the P-M group did not change. In the second phase of the trial, the average weight and BMI of the M-M group was unchanged relative to the end of phase I, while that of the P-M group was significantly reduced. These results indicate that metformin is effective in reducing weight and maintaining weight loss in children who experience weight gain as a side effect of atypical antipsychotic medications. Therefore, use of metformin may be an effective management approach for controlling weight gain. Although the researchers noted that the group who started metformin experienced a four- to eight-week delay before weight reduction became apparent, longer-term outcomes indicate that children with ASD continue to benefit from use of an atypical antipsychotic medication.

Parent-delivered early intervention in infants at risk for ASD: effects on electrophysiological and habituation measures of social attention
Jones EJ, Dawson G, Kelly J, Estes A, Webb SJ. Autism Res.. 2017 May;10(5):961-972. [PMID: 28244271]

Research suggests that children with ASD may have impairments in social attention that can be measured through brain activity detectable before behavioral signs arise. Early detection and diagnosis of ASD is important because early intervention can improve social attention and other outcomes. Importantly, research suggests that interventions administered by parents can increase parental responsiveness to infants’ communication cues. Furthermore, these at-home interventions may be beneficial for at-risk populations, particularly for infants with developmental disabilities and for families who live in low-resource communities. In this study, researchers tested a parent-mediated intervention designed to promote parent-infant interaction with the goal of proactively stimulating brain activity important to social attention. Infants at age 6 months were identified as either high-risk (the infant had an older sibling with ASD) or low-risk. Infants in the high-risk groups were randomized to receive either assessment and monitoring only, or a promoting first relationships (PFR) intervention administered between age 9 months and 11 months. The PFR intervention involved a trained mental health professional who met with the caregiver and their infant approximately 1 hour per week for 10 weeks and focused on promoting caregiver-infant interaction and infant social development.

Researchers assessed the social attention of the infants at 6 (baseline), 12 (endpoint), and 18-months (follow-up). At each time point, the researchers measured the children’s 1) habituation to (time spent looking at) faces and objects, 2) brain activity in response to social and non-social videos, and 3) brain activity in response to faces and objects. Brain activity was measured using electroencephalographic (EEG) recordings of electrical activity in the brain. They predicted that the children who participated in the PFR intervention would show decreased habituation time to faces (indicating that the children learned to more quickly encode and recall a novel face), increased brain activity in response to social videos, and increased brain activity in response to faces rather than objects.

The researchers found that children who received the PFR intervention showed decreased habituation time to faces over both time periods, indicating an improvement in learning and information processing. This effect was not seen in the children who did not participate in the PFR intervention. Additionally, the children who participated in the PFR intervention showed increased brain activity in response to both social and non-social videos, as compared to the children in the non-intervention group. Finally, children who participated in the PFR intervention showed larger and more prolonged neural responses to faces than to objects, indicating more in-depth processing of social cues. The children who did not participate in the intervention showed larger and more prolonged responses to objects than to faces.

These findings suggest that initiating interventions prior to the onset of symptoms in high-familial risk children may reduce early signs of ASD symptoms and cascading effects of having difficulty in processing social cues. As high-familial risk children have about a 20% chance of developing ASD, these interventions might be valuable to improving outcomes in these children.

Question 4

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