Pam Harrison

May 22, 2014

ATLANTA ― A subgroup of infants who have siblings who develop autism spectrum disorder (ASD) show milder declines in early eye-looking patterns that begin to self-correct at approximately 9 months of age, new research shows.

By 18 months of age, this same group of infants has more typical development profiles than their siblings who are later diagnosed with ASD who have declines in eye-looking patterns that begin in the first 6 months of life.

Findings from the current study may reveal a pathway to sibling resilience against developing ASD to which they are otherwise greatly predisposed.

"The important take-away from this study is that for unaffected siblings as well as typically developing infants, there is no difference in levels of eye-looking and no difference in the developmental transitions that happen over time," study investigator Warren Jones, PhD, director of research, Marcus Autism Center, Children's Healthcare of Atlanta, and assistant professor of pediatrics, Emory University School of Medicine, Atlanta, Georgia, said a press conference here at the 13th Annual International Meeting for Autism Research (IMFAR).

"What really excited us, however, is the difference we observed in the developmental profiles of infants who were later diagnosed with autism relative to those infants who show some symptoms of atypical social development but who do not meet full diagnostic criteria for ASD. These infants have vulnerabilities, but the vulnerabilities are not so concerning as to warrant diagnosis, and [it is] these infants who have a more positive prognosis than infants later diagnosed with autism," Dr. Jones added.

Earlier Study

In an earlier 2013 study published in Nature and reported by Medscape Medical News at that time, Dr. Jones and colleague Ami Klin, PhD, who is also with Emory University School of Medicine, compared eye-tracking "growth charts" of social visual engagement in infants at high risk for ASD and typically developing infants. Some 13 infants were diagnosed with ASD at 36 months of age; 29 were typically developing infants.

At 10 different time points between 2 and 24 months of age, researchers measured the infants' eye movements as the children watched video scenes of a caregiver.

Researchers then calculated the percentage of time each child fixated on the caregiver's eyes, mouth, and body as well as on the nonhuman spaces in the images.

"Long before infants can crawl or walk, they explore the world by looking at it," Dr. Jones said. "And infants later diagnosed with autism exhibited a steady decline in eye-looking from the second month of life until month 24."

Importantly, decline in eye fixation in the first 6 months of life in this earlier study predicted the diagnosis of ASD at the ages of 24 and 36 months. Decline in eye fixation in the first 12 months of life also predicted the child's level of disability at the ages of 24 and 36 months, as Dr. Jones added.

For this study, researchers asked the question, What separates those infants who are later diagnosed with autism from the ones who have "shadow" ASD, otherwise referred to as broader autism phenotype, or BAP, but who do not meet full ASD criteria later on in life?

The group of interest for the current analysis included 18 infants who were unaffected by ASD at 36 months and 10 infants who had BAP. Investigators then divided this subgroup of infants on the basis of early decline in eye fixation or the absence of such decline.

Sixteen infants in the overall subgroup had no sign of early decline in eye fixation, and 15 out of this subgroup were clinically unaffected at follow-up. One infant was, however, identified as having BAP.

Another 12 infants out of the overall subgroup did show signs of early decline in eye fixation, and 9 of these infants were identified at follow-up as having BAP; 3 remained clinically unaffected.

It was in these 9 infants in whom eye fixation, though initially in decline, changed course and among whom investigators documented positive increases in time spent fixing on other people's eyes at 18 months of age.

These results suggest an early loss of traction in social engagement for infants who show more resilient outcomes ― a "slippage of the disks," as Dr. Jones noted, but then this subgroup catches up, and there is overt evidence of a developing change in behavior.

"Eye-looking is neither causing nor correcting autism, it's a marker: a manifestation of the derailment of typical social development [that occurs in ASD]," Dr. Jones told Medscape Medical News. "What's exciting about these new findings is that we're tracking the way in which some infants change their behavior and ultimately end up with more social skills than their affected siblings. We need to understand the underlying neurobiology that accompanies these changes in early development, and being able to observe and quantify these differences is the first step."

Seminal Research

Asked by Medscape Medical News to comment on the clinical relevance of the findings, Laura Klinger, PhD, University of North Carolina TEACCH Autism Program, Chapel Hill, said this represented "very seminal research" in that it showed 2 groups of children who look identical at 2 months, yet one group goes on to develop autism and the other group shows resiliency and does not.

"This is truly one of the first datasets we've had where we see differences at 2 months, where one group ends up correcting and not having atypical behaviors later on in life, whereas the other group does not," she added.

What would be helpful, as Dr. Klinger suggested, is to target these 2 groups of infants with atypical eye-tracking behavior to see whether interventions might be able to move more of them into a typical pattern as early as the first year of life.

"We know that early intervention in the first few years of life makes a significant difference on long-term outcomes for individuals with autism," Dr. Klinger noted. "So researchers around the globe have been looking at whether we can identify early signs of autism in the first year of life to promote earlier and earlier intervention. That is one of the main themes of this year's meeting at IMFAR, and it's an important one to explore."

The study was funded by the National Institute of Mental Health, the Simons Foundation, the Marcus Foundation, and the Whitehead Foundation. The investigators have disclosed no relevant financial relationships.

13th Annual International Meeting for Autism Research (IMFAR). Abstract 145.002. Presented May 16, 2014.

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