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Summary of Advances Cover 2016
Summary of Advance
In Autism Spectrum Disorder Research
Question 1: When Should I Be Concerned?

Reduced engagement with social stimuli in 6-month-old infants with later autism spectrum disorder: a longitudinal prospective study of infants at high familial risk
Jones EJ, Venema K, Earl R, Lowy R, Barnes K, Estes A, Dawson G, Webb SJ. J Neurodev Disord. 2016 Mar 15;8:7. [PMID: 26981158]

The average age of an ASD diagnosis in the U.S. is approximately 4 years old. Research has shown that up to 20% of infants who have an older sibling with ASD will also be diagnosed with ASD later in their lives. Parents may suspect ASD prior to a formal diagnosis, particularly if their infant has a sibling with an ASD diagnosis.

Early diagnosis is important for effective ASD intervention. It is therefore important to identify characteristics of ASD that may be measurable in infancy. Social attention, which is the ability to interact and orient eye contact with another person, is a common deficit in ASD, and may occur as early as at 6 to 12 months old. Furthermore, it is possible that there are measurable differences in brain activity that might be detectable even before the full manifestation of autism is present. The goal of this study was to determine whether 6- and 12-month-old infants who later develop ASD differ from typically developing infants in terms of their neural responses and attention patterns to social versus non-social stimuli.

In this study, the researchers first conducted experiments to determine patterns of social attention in typically developing infants. Children at 6 and 12 months old were shown colored images of non-social attention stimuli (ageappropriate objects) and social attention stimuli (different faces). Attention was measured using habituation (when the amount of “look time” at an image declines after consecutive looks) and event-related potential (ERP, which records brain activity simultaneous with the presentation of the images to correlate attention engagement in the brain). The results of this experiment confirmed that, in typically developing infants, a longer duration of attention was given to faces than to objects, as reflected in both habituation patterns and neural responses.

In the second part of the study, researchers examined the differences between infants with an older sibling diagnosed with ASD (high risk) and infants without an older sibling diagnosed with ASD (low risk). The same social attention experiments were conducted across both groups. At 24 months of age, the same infants were clinically assessed for ASD. The results of this experiment showed that 6-month-old high-risk infants who were later diagnosed with ASD at 24 months displayed a disruption in the ability to sustain attention in general—a finding both in habituation patterns and in neural response times. The 6-month-old infants at high risk for ASD and later diagnosed with ASD at 24 months showed disrupted habituation specifically to faces and showed a more robust (higher amplitude) neural response to objects than faces, a pattern not evident in the infants who did not develop ASD. At 12 months, the difference between the groups was less apparent. High-risk infants who did not develop ASD did not show reduced attention during these experiments.

These findings suggest that high-risk infants who are later diagnosed with ASD have disrupted or delayed attention engagement for social stimuli at 6 months old. Differences in neural responses to social versus nonsocial information in high-risk infants who later develop ASD are evident by 6 months of age and precede the development of the full behavioral syndrome. As the child ages and developmental milestones are passed, this early disruption in social attention may cascade into reduced social engagement.

School-age outcomes of infants at risk for autism spectrum disorder
Miller M, Iosif AM, Young GS, Hill M, Phelps Hanzel E, Hutman T, Johnson S, Ozonoff S. Autism Res. 2016 Jun;9(6):632-42. [PMID: 26451968]

ASD occurs at a significantly higher rate in children who have an older sibling with ASD compared with those who do not. Recent studies have investigated the developmental characteristics of such high-risk children from infancy to toddler age, but few of these studies have been extended to include school-age children. High-risk, school-age children sometimes may not meet diagnostic criteria for ASD, but still exhibit clinical concerns such as attention-deficit/hyperactivity disorder (ADHD), anxiety, depression, and learning issues, as well as a broader autism phenotype—a constellation of subclinical, ASD-related difficulties such as deficiencies in language, social skills, motor function, and behavior. Therefore, studies of non-ASD, high-risk children are critical to improve diagnosis and treatment of these ASD-related clinical concerns.

This study followed children from infancy to school-age (up to 9 years old) who were high-risk (younger siblings of children with ASD) and low-risk (younger siblings of typically developing children) to:

  • Determine rates of dysfunction across assessment scores for cognition, language, psychopathology, and ASD symptoms
  • Examine the rate of ASD-related clinical concerns
  • Compare clinical concerns outcomes across time—at 36 months and school-age

When comparing assessment scores across groups, the researchers found that 43% of children in the high-risk group and 12% of children in the low-risk group had one or more clinically elevated assessment scores. The most pronounced deficiencies in the high-risk group were seen in the Social Responsiveness Scale (SRS, which measures social, communication, and repetitive/stereotyped behaviors) and the Child Behavior Checklist (CBCL, which measures mood, attention, behaviors, and social issues). The rate of ASD-related clinical concerns was 38% for children in the high-risk group as compared to 13% for children in the low-risk group. The most frequently observed clinical concerns were broader autism phenotype and ADHD.

There were some differences in outcomes across age, with almost 12% of high-risk children exhibiting clinical concerns at school-age but not earlier in infancy, and 17% of high-risk children exhibiting clinical concerns at infancy that seemed to have improved by school age. However, most high-risk children showed consistency in clinical concerns across time. Notably, the proportion of high-risk children who exhibited clinical concerns was consistent with the proportion of high-risk children who received elevated scores on the SRS and CBCL. This suggests that nonverbal cognitive and language impairment might not be a primary area of concern in school-age children—an important finding considering that schools focus on cognitive and language functioning and may miss the challenges that are more relevant to school-age children. These results suggest that clinical concerns associated with high-risk infants and toddlers may continue to school-age, and that these children would benefit from continued screening, specifically expanded into areas of social responsiveness and skills, ADHD, and mood disorders.

Question 1

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