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Summary of Advances Cover 2013
Summary of Advance
In Autism Spectrum Disorder Research
Question 4: Which Treatments and Interventions Will Help?

Preschool based JASPER intervention in minimally verbal children with autism: pilot RCT - Goods KS, Ishijima E, Chang Y-C, Kasari C. J Autism Dev. Disord. 2013 May;43(5):1050–1056. [PMID: 22965298]

Children with ASD who attain verbal skills by 5 years of age have been found to demonstrate the best social outcomes. Early intervention studies have found that improvement in such skills as joint attention can positively impact the development of verbal communication in these children. Traditionally, these studies have only evaluated children meeting specific developmental age or intellectual ability/IQ criteria, thus overlooking children with the greatest developmental impairments, including those who have made minimal progress in acquiring spoken language skills (those who are "minimally verbal"). As a result, little knowledge exists concerning the impact that early interventions may have on improving communication in minimally verbal children with ASD. To address this gap, researchers in the current study specifically focused on minimally verbal children with ASD who had not been responsive to intensive behavioral therapy, and conducted a randomized controlled trial of 24 sessions over 12 weeks to evaluate whether a novel play-based intervention employing communicative gestures, known as Joint Attention Symbolic Play Engagement and Regulation (JASPER), would improve social communication outcomes. Fifteen preschool aged children (3 to 5 years old) with a clinical diagnosis of ASD and spoken language skills of fewer than 10 spontaneous, functional, and communicative words initially took part in this study, with 11 children completing the study. Baseline assessments were conducted prior to the start of the study and included diagnostic confirmation of ASD using the Autism Diagnostic Observation Scale (ADOS), the Mullen Scales of Early Learning (MSEL) to assess mental age and development (e. g. , visual reception, fine motor, receptive language, and expressive language skills), and the Reynell Developmental Language Scales (RDLS) to assess verbal comprehension. All children in this study participated in 30 hour-per-week behaviorally based interventions as well as speech and occupational therapy. Seven of the children were randomly assigned to a treatment group where they were pulled twice a week from their standard weekly interventions for 30-minute sessions of JASPER (considered a "low dose" therapy), while the control group children only received their standard 30 hour-per-week speech and occupational therapies. After 12 weeks, researchers observed that children who had received JASPER demonstrated less repetitive patterns while playing, initiated more social gestures in the classroom setting, and indicated greater attention engagement with others, compared to those who had not received JASPER. No change was observed in generalized joint attention measures, though that was another targeted behavior. The researchers hypothesized that perhaps they saw changes in play and engagement related behaviors because spontaneous communication changes naturally come later in the developmental progression, or perhaps because more time would be needed for that change to develop. Investigators thus concluded that brief interventions show much potential in targeting joint attention and play skills and can result in the improvement of core deficits in minimally verbal children with ASD.

Oxytocin enhances brain function in children with autism - Gordon I, Vander Wyk BC, Bennett RH, Cordeaux C, Lucas MV, Eilbott JA, Zagoory-Sharon O, Leckman JF, Feldman R, Pelphrey KA. Proc Natl Acad Sci. 2013 Dec;110(52):20953–20958. [PMID: 24297883]

Difficulty with social interaction is one of the hallmarks of ASD. A number of ASD treatments have targeted social impairment; however, there is no established drug treatment to address this aspect of the disorder. Researchers have recently begun to examine oxytocin, a naturally occurring hormone secreted by the brain's pituitary gland, as a drug candidate to ameliorate the social impairments found in ASD. Previous work in children and adults with ASD suggests that oxytocin treatment can increase social cognition, decrease repetitive behaviors, and enhance willingness to interact socially. Although a number of these behavioral improvements have been documented, overall results of oxytocin treatment have been mixed. While studies of changes in the brain activity of adults in response to oxytocin have shed some light on the behavioral effects observed in adults, there has been a gap in knowledge regarding the effects of oxytocin on the brain activity of children. Filling this knowledge gap has become even more important, as a number of clinical trials have recently launched to investigate the effects of oxytocin administration in children with ASD.

Investigators in the current study used a double blind, crossover trial design (having each person participate once with placebo and once with the experimental treatment, but without knowing which was which) to study the impact of oxytocin on brain activity in children and adolescents with ASD using brain imaging. After treatment with an oxytocin nasal spray, activity in the brains of 17 children and adolescents (8 to 16.5 years old) was observed using functional magnetic resonance imaging (fMRI) as they performed a task that involved making social judgments (labeling a mental state based on viewing a picture of a person's eyes) or non-social judgments (labeling the category when shown a picture of a motor vehicle). The researchers found that oxytocin treatment, but not placebo treatment, had distinct effects on brain activity. Oxytocin administration increased brain activity during social judgments in specific brain regions that are important for social attention, reward, perception, and reasoning about others' mental states—all of which are under-active in ASD. A subset of these social brain areas showed more activity as the amount of oxytocin measured in the body increased. Interestingly, oxytocin treatment also resulted in decreased brain activity in social brain areas during non-social tasks. The researchers hypothesized that by enhancing responses in social situations and suppressing responses in non-social situations, oxytocin focuses this brain circuitry on processing social information. Though oxytocin caused a visible change in brain activity, the study results did not demonstrate an impact on the children's autism behavioral symptoms. The authors suggested that perhaps behavioral improvements in response to oxytocin treatment can only be observed when tested in a richer, more realistic social context that includes opportunities for social learning. The results of this study, showing how oxytocin administration alters brain activity in areas important for social cognition in children with ASD, suggest that oxytocin holds promise as a treatment for these individuals, and also refines its potential role. If oxytocin primes the brain for responding to social input, it may be most beneficial if delivered immediately before evidence-based behavioral interventions, to maximize their benefit.

Question 4

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