Autism Sibling Studies Beginning to Yield Data

WASHINGTON – Studies of the younger siblings of children with autism spectrum disorders are beginning to yield information that has important implications for screening, reducing the age at diagnosis, and identifying the window of time during which still unidentified interventions might be able to affect the course, according to experts who spoke at the annual convention of the American Psychological Association.

During a symposium on early development and predictors of outcomes in infant siblings of children with autism, several experts summarized the results of studies evaluating the emergence of autism spectrum disorders (ASD) and ASD-like symptoms in the younger siblings of children with ASD, as well as tools that are being studied in high-risk sibling studies as potential methods of diagnosing ASD earlier.

© MattZ90/Thinkstockphotos.com

The risk of ASD is 1 in 68 in the general population, but is almost 1 in 5 among the siblings of children diagnosed with ASD. An additional one in five siblings will have "shadow symptoms" of autism, which refers to children with some of the symptomatology but not enough to merit a diagnosis. In addition, another 1 in 10 will have nonautism developmental delays.

Therefore, about 50% of infant siblings of children with ASD "are vulnerable in their development to some degree, so that’s why we’re studying them so closely," said one of the speakers, Celine Saulnier, Ph.D., clinical director for research at the Marcus Autism Center, Emory University, Atlanta.

During the symposium, Alice Carter, Ph.D., professor of clinical psychology at the University of Massachusetts, Boston, provided the results of a prospective study that identified high-risk siblings who exhibited some ASD-like behaviors early on but were not diagnosed with autism at age 3.

A growing body of literature focusing on milder ASD symptoms in relatives of people diagnosed with ASD indicates that about 20%-30% of children who are at high genetic risk develop some symptoms of autism but not enough symptoms or symptoms that are severe enough to make the diagnosis, she said. This is often referred to as the broader autism phenotype (BAP), which affects an estimated 19% of unaffected siblings at age 12 months.

The prospective study followed 26 infants who had older siblings with ASD, the high-risk group, to 33 infants whose older siblings had typical development. None of these infants met the diagnostic criteria for ASD at 18, 24, and 36 months. Parents completed a questionnaire, the Brief Infant-Toddler Social Emotional Assessment (BITSEA), when the child was 12, 18, and 24 months.

Based on the results of these parent reports, unaffected siblings of the children with autism "displayed more ASD-relevant problem behaviors than the unaffected infants with typically developing siblings," Dr. Carter said. The former also appear to show "a somewhat different trajectory of these behaviors over time," with scores that were significantly different at 18 months from the low-risk group but "converging" by the time they were aged 24 months, when they appeared to be comparable.

These results support the importance of monitoring younger siblings of children diagnosed with ASD for the emergence of ASD symptoms with routine developmental screening and surveillance, "as they may benefit from early intervention services," Dr. Carter said. But even without such services, children may follow the "self-righting trajectory that takes them back on a normative developmental course," which was evident in the study, she added. (She noted that the limitations of the study included the small sample size in the Boston area. In addition, the participants, were mostly white and had higher than average annual family incomes above $65,000.)

Dr. Carter said future challenges will be to distinguish between three different groups of infants who do not meet the full criteria for an ASD diagnosis: Those manifesting symptoms that mark the beginning of the pathway toward ASD or the emergence of ASD (prodromal ASD); those whose symptoms are likely to resolve; and those who show signs of ASD that "will endure and reflect the broader autism phenotype." The primary target for early screening and detection is the identification of the prodromal group, she added.

Other studies involving high-risk siblings include the UC Davis Infant Sibling Study, which is prospectively following infants with an older sibling who has autism and infants with an older sibling who is developing typically, following the infants up to age 3 years, through the window of autism risk. The second phase of the study followed a small group of infants, enrolled between 6 and 9 months, to age 3 years, with testing that included retrospective and prospective parent ratings, and prospective examiner ratings. Most (89%) of the children who developed ASD showed a regressive onset in terms of their social communication behaviors.

Parents were able to identify those trajectories, indicating impending ASD, with prospective reports, "but not as well retrospectively" with the Autism Diagnostic Interview-Revised (ADI-R), which was accurate in only 30% of cases," said Meghan Miller, Ph.D., a postdoctoral fellow at the University of California, Davis, MIND Institute. These results suggest that while parental reports of regression on the ADI-R can be accurate, they might only pick up "the tip of the iceberg," she noted.

The findings, based on a small sample, raise concerns about the use of the ADI-R and other retrospective measures in research, but do provide "some hope for early screening using parent report data," Dr. Miller pointed out. Such reports would be more feasible than neuroimaging, eye tracking, and other sophisticated testing that could be used over several well child visits, to detect declines and help determine which children should be further evaluated further or referred for interventions, she added. Phase III of the study is currently underway.

In other sibling studies, Dr. Saulnier discussed the use of eye-tracking testing in studies that prospectively followed high-risk infants whose siblings have been diagnosed with ASD and low-risk infants with typically developing siblings.

Under eye-tracking methodology, the child watches prerecorded movies on a monitor of women acting as caregivers, singing, and talking to an infant. It is well established that when viewing a social scene, typically developing adults focus on the eye region of the face, but those with autism look less at the eyes and significantly more at the mouth, body, and objects in the social scene. Those findings have been replicated in school-aged children, adolescents, and toddlers down to aged 2 years, she noted.

In infant studies, eye-tracking testing is performed at least 10 times from birth to age 3, with vocal recordings and clinical assessments at different periods.

Summarizing the findings, Dr. Saulnier said infants at low risk who have a typical outcome show a steady fixation of eye gaze from birth. But infants who are at high risk for ASD and "develop ASD by age 3 show a rapid decline in eye fixation between 2 and 6 months of age that is more predictive of ASD than any clinical measure."

Autism cannot be diagnosed with this test alone, she said. (Most of this work was conducted at the Yale Child Study Center, before she moved to Emory, she said.)

She provided examples of a 5-month-old low-risk infant, who developed typically and focused at the eye region of the face, contrasting with another 5-month old infant, who went on to develop autism by agd 3, who was not looking at the eye region of the face, focusing on the mouth, body, and objects.

Another example she showed was an infant who had normal results at 3 and 6 months, but by 9 months, the researchers started to see a shift, which she described as the "unfolding of autism." This child was diagnosed with autism at 12 months. She added, however, that it is rare to see that symptomatology so early and pronounced.

While it would be assumed that the children who go on to develop autism manifest the lack of eye fixation from birth, another finding from eye fixation studies is that the opposite is true, and "babies who went on to develop autism actually had significantly more eye fixation in the first 2 months of life," Dr. Saulnier said.

Typically developing infants maintain this focus on the eyes, "but whatever is happening in autism to make social monitoring not as salient, they’re trailing off, and you’re seeing this derailment in this eye fixation."

Other results of eye-tracking sibling studies might provide information about a window of opportunity – at about age 9-12 months – for an intervention "that could capitalize on the potential for resilience, she noted.

In infants whose older siblings have ASD and are either unaffected or have "shadow symptoms" of autism at age 3 years, eye-tracking results indicate that after reduced eye fixation, they exhibit a "course correction" in increased eye fixation that appears to start around 9 months of age.

Why this occurs is not understood, but this observation sheds some light on a possible window of time during which something could be done, before autism fully unfolds, such as coaching strategies for parents on keeping their child engaged "to produce a course correction if it wasn’t naturally going to occur," Dr. Saulnier said.

She and her associates are now conducting a randomized, controlled study of infants at risk at 12 months, evaluating a potential way to correct the course.

Among the goals in the future is to reduce the mean age of an autism diagnosis so that, once recognized, effective interventions can be started that could affect outcomes, she said. Although autism can be reliably diagnosed by 18-24 months, the mean age of ASD diagnosis is currently about 4.5 years, she noted.

Dr. Carter disclosed that she is one of the developers of the BITSEA screening tool, used in the study she presented. Dr. Saulnier had no disclosures; the studies she presented received support from the National Institute of Mental Health, the National Institute of Child Health and Human Development, the Marcus Foundation, and the Whitehead and Woodruff Foundations. Dr. Miller said the UCSD study has been funded by NIMH, Autism Speaks, and the MINDlist.

A tutorial on recognizing the early signs of ASD, developed by the Kennedy Krieger Institute, Baltimore,is available at https://www.youtube.com/watch?v=YtvP5A5OHpU.

[email protected]

WASHINGTON – Studies of the younger siblings of children with autism spectrum disorders are beginning to yield information that has important implications for screening, reducing the age at diagnosis, and identifying the window of time during which still unidentified interventions might be able to affect the course, according to experts who spoke at the annual convention of the American Psychological Association.

During a symposium on early development and predictors of outcomes in infant siblings of children with autism, several experts summarized the results of studies evaluating the emergence of autism spectrum disorders (ASD) and ASD-like symptoms in the younger siblings of children with ASD, as well as tools that are being studied in high-risk sibling studies as potential methods of diagnosing ASD earlier.

© MattZ90/Thinkstockphotos.com

The risk of ASD is 1 in 68 in the general population, but is almost 1 in 5 among the siblings of children diagnosed with ASD. An additional one in five siblings will have "shadow symptoms" of autism, which refers to children with some of the symptomatology but not enough to merit a diagnosis. In addition, another 1 in 10 will have nonautism developmental delays.

Therefore, about 50% of infant siblings of children with ASD "are vulnerable in their development to some degree, so that’s why we’re studying them so closely," said one of the speakers, Celine Saulnier, Ph.D., clinical director for research at the Marcus Autism Center, Emory University, Atlanta.

During the symposium, Alice Carter, Ph.D., professor of clinical psychology at the University of Massachusetts, Boston, provided the results of a prospective study that identified high-risk siblings who exhibited some ASD-like behaviors early on but were not diagnosed with autism at age 3.

A growing body of literature focusing on milder ASD symptoms in relatives of people diagnosed with ASD indicates that about 20%-30% of children who are at high genetic risk develop some symptoms of autism but not enough symptoms or symptoms that are severe enough to make the diagnosis, she said. This is often referred to as the broader autism phenotype (BAP), which affects an estimated 19% of unaffected siblings at age 12 months.

The prospective study followed 26 infants who had older siblings with ASD, the high-risk group, to 33 infants whose older siblings had typical development. None of these infants met the diagnostic criteria for ASD at 18, 24, and 36 months. Parents completed a questionnaire, the Brief Infant-Toddler Social Emotional Assessment (BITSEA), when the child was 12, 18, and 24 months.

Based on the results of these parent reports, unaffected siblings of the children with autism "displayed more ASD-relevant problem behaviors than the unaffected infants with typically developing siblings," Dr. Carter said. The former also appear to show "a somewhat different trajectory of these behaviors over time," with scores that were significantly different at 18 months from the low-risk group but "converging" by the time they were aged 24 months, when they appeared to be comparable.

These results support the importance of monitoring younger siblings of children diagnosed with ASD for the emergence of ASD symptoms with routine developmental screening and surveillance, "as they may benefit from early intervention services," Dr. Carter said. But even without such services, children may follow the "self-righting trajectory that takes them back on a normative developmental course," which was evident in the study, she added. (She noted that the limitations of the study included the small sample size in the Boston area. In addition, the participants, were mostly white and had higher than average annual family incomes above $65,000.)

Dr. Carter said future challenges will be to distinguish between three different groups of infants who do not meet the full criteria for an ASD diagnosis: Those manifesting symptoms that mark the beginning of the pathway toward ASD or the emergence of ASD (prodromal ASD); those whose symptoms are likely to resolve; and those who show signs of ASD that "will endure and reflect the broader autism phenotype." The primary target for early screening and detection is the identification of the prodromal group, she added.

Other studies involving high-risk siblings include the UC Davis Infant Sibling Study, which is prospectively following infants with an older sibling who has autism and infants with an older sibling who is developing typically, following the infants up to age 3 years, through the window of autism risk. The second phase of the study followed a small group of infants, enrolled between 6 and 9 months, to age 3 years, with testing that included retrospective and prospective parent ratings, and prospective examiner ratings. Most (89%) of the children who developed ASD showed a regressive onset in terms of their social communication behaviors.

Parents were able to identify those trajectories, indicating impending ASD, with prospective reports, "but not as well retrospectively" with the Autism Diagnostic Interview-Revised (ADI-R), which was accurate in only 30% of cases," said Meghan Miller, Ph.D., a postdoctoral fellow at the University of California, Davis, MIND Institute. These results suggest that while parental reports of regression on the ADI-R can be accurate, they might only pick up "the tip of the iceberg," she noted.

The findings, based on a small sample, raise concerns about the use of the ADI-R and other retrospective measures in research, but do provide "some hope for early screening using parent report data," Dr. Miller pointed out. Such reports would be more feasible than neuroimaging, eye tracking, and other sophisticated testing that could be used over several well child visits, to detect declines and help determine which children should be further evaluated further or referred for interventions, she added. Phase III of the study is currently underway.

In other sibling studies, Dr. Saulnier discussed the use of eye-tracking testing in studies that prospectively followed high-risk infants whose siblings have been diagnosed with ASD and low-risk infants with typically developing siblings.

Under eye-tracking methodology, the child watches prerecorded movies on a monitor of women acting as caregivers, singing, and talking to an infant. It is well established that when viewing a social scene, typically developing adults focus on the eye region of the face, but those with autism look less at the eyes and significantly more at the mouth, body, and objects in the social scene. Those findings have been replicated in school-aged children, adolescents, and toddlers down to aged 2 years, she noted.

In infant studies, eye-tracking testing is performed at least 10 times from birth to age 3, with vocal recordings and clinical assessments at different periods.

Summarizing the findings, Dr. Saulnier said infants at low risk who have a typical outcome show a steady fixation of eye gaze from birth. But infants who are at high risk for ASD and "develop ASD by age 3 show a rapid decline in eye fixation between 2 and 6 months of age that is more predictive of ASD than any clinical measure."

Autism cannot be diagnosed with this test alone, she said. (Most of this work was conducted at the Yale Child Study Center, before she moved to Emory, she said.)

She provided examples of a 5-month-old low-risk infant, who developed typically and focused at the eye region of the face, contrasting with another 5-month old infant, who went on to develop autism by agd 3, who was not looking at the eye region of the face, focusing on the mouth, body, and objects.

Another example she showed was an infant who had normal results at 3 and 6 months, but by 9 months, the researchers started to see a shift, which she described as the "unfolding of autism." This child was diagnosed with autism at 12 months. She added, however, that it is rare to see that symptomatology so early and pronounced.

While it would be assumed that the children who go on to develop autism manifest the lack of eye fixation from birth, another finding from eye fixation studies is that the opposite is true, and "babies who went on to develop autism actually had significantly more eye fixation in the first 2 months of life," Dr. Saulnier said.

Typically developing infants maintain this focus on the eyes, "but whatever is happening in autism to make social monitoring not as salient, they’re trailing off, and you’re seeing this derailment in this eye fixation."

Other results of eye-tracking sibling studies might provide information about a window of opportunity – at about age 9-12 months – for an intervention "that could capitalize on the potential for resilience, she noted.

In infants whose older siblings have ASD and are either unaffected or have "shadow symptoms" of autism at age 3 years, eye-tracking results indicate that after reduced eye fixation, they exhibit a "course correction" in increased eye fixation that appears to start around 9 months of age.

Why this occurs is not understood, but this observation sheds some light on a possible window of time during which something could be done, before autism fully unfolds, such as coaching strategies for parents on keeping their child engaged "to produce a course correction if it wasn’t naturally going to occur," Dr. Saulnier said.

She and her associates are now conducting a randomized, controlled study of infants at risk at 12 months, evaluating a potential way to correct the course.

Among the goals in the future is to reduce the mean age of an autism diagnosis so that, once recognized, effective interventions can be started that could affect outcomes, she said. Although autism can be reliably diagnosed by 18-24 months, the mean age of ASD diagnosis is currently about 4.5 years, she noted.

Dr. Carter disclosed that she is one of the developers of the BITSEA screening tool, used in the study she presented. Dr. Saulnier had no disclosures; the studies she presented received support from the National Institute of Mental Health, the National Institute of Child Health and Human Development, the Marcus Foundation, and the Whitehead and Woodruff Foundations. Dr. Miller said the UCSD study has been funded by NIMH, Autism Speaks, and the MINDlist.

A tutorial on recognizing the early signs of ASD, developed by the Kennedy Krieger Institute, Baltimore,is available at https://www.youtube.com/watch?v=YtvP5A5OHpU.

[email protected]

WASHINGTON – Studies of the younger siblings of children with autism spectrum disorders are beginning to yield information that has important implications for screening, reducing the age at diagnosis, and identifying the window of time during which still unidentified interventions might be able to affect the course, according to experts who spoke at the annual convention of the American Psychological Association.

During a symposium on early development and predictors of outcomes in infant siblings of children with autism, several experts summarized the results of studies evaluating the emergence of autism spectrum disorders (ASD) and ASD-like symptoms in the younger siblings of children with ASD, as well as tools that are being studied in high-risk sibling studies as potential methods of diagnosing ASD earlier.

© MattZ90/Thinkstockphotos.com

The risk of ASD is 1 in 68 in the general population, but is almost 1 in 5 among the siblings of children diagnosed with ASD. An additional one in five siblings will have "shadow symptoms" of autism, which refers to children with some of the symptomatology but not enough to merit a diagnosis. In addition, another 1 in 10 will have nonautism developmental delays.

Therefore, about 50% of infant siblings of children with ASD "are vulnerable in their development to some degree, so that’s why we’re studying them so closely," said one of the speakers, Celine Saulnier, Ph.D., clinical director for research at the Marcus Autism Center, Emory University, Atlanta.

During the symposium, Alice Carter, Ph.D., professor of clinical psychology at the University of Massachusetts, Boston, provided the results of a prospective study that identified high-risk siblings who exhibited some ASD-like behaviors early on but were not diagnosed with autism at age 3.

A growing body of literature focusing on milder ASD symptoms in relatives of people diagnosed with ASD indicates that about 20%-30% of children who are at high genetic risk develop some symptoms of autism but not enough symptoms or symptoms that are severe enough to make the diagnosis, she said. This is often referred to as the broader autism phenotype (BAP), which affects an estimated 19% of unaffected siblings at age 12 months.

The prospective study followed 26 infants who had older siblings with ASD, the high-risk group, to 33 infants whose older siblings had typical development. None of these infants met the diagnostic criteria for ASD at 18, 24, and 36 months. Parents completed a questionnaire, the Brief Infant-Toddler Social Emotional Assessment (BITSEA), when the child was 12, 18, and 24 months.

Based on the results of these parent reports, unaffected siblings of the children with autism "displayed more ASD-relevant problem behaviors than the unaffected infants with typically developing siblings," Dr. Carter said. The former also appear to show "a somewhat different trajectory of these behaviors over time," with scores that were significantly different at 18 months from the low-risk group but "converging" by the time they were aged 24 months, when they appeared to be comparable.

These results support the importance of monitoring younger siblings of children diagnosed with ASD for the emergence of ASD symptoms with routine developmental screening and surveillance, "as they may benefit from early intervention services," Dr. Carter said. But even without such services, children may follow the "self-righting trajectory that takes them back on a normative developmental course," which was evident in the study, she added. (She noted that the limitations of the study included the small sample size in the Boston area. In addition, the participants, were mostly white and had higher than average annual family incomes above $65,000.)

Dr. Carter said future challenges will be to distinguish between three different groups of infants who do not meet the full criteria for an ASD diagnosis: Those manifesting symptoms that mark the beginning of the pathway toward ASD or the emergence of ASD (prodromal ASD); those whose symptoms are likely to resolve; and those who show signs of ASD that "will endure and reflect the broader autism phenotype." The primary target for early screening and detection is the identification of the prodromal group, she added.

Other studies involving high-risk siblings include the UC Davis Infant Sibling Study, which is prospectively following infants with an older sibling who has autism and infants with an older sibling who is developing typically, following the infants up to age 3 years, through the window of autism risk. The second phase of the study followed a small group of infants, enrolled between 6 and 9 months, to age 3 years, with testing that included retrospective and prospective parent ratings, and prospective examiner ratings. Most (89%) of the children who developed ASD showed a regressive onset in terms of their social communication behaviors.

Parents were able to identify those trajectories, indicating impending ASD, with prospective reports, "but not as well retrospectively" with the Autism Diagnostic Interview-Revised (ADI-R), which was accurate in only 30% of cases," said Meghan Miller, Ph.D., a postdoctoral fellow at the University of California, Davis, MIND Institute. These results suggest that while parental reports of regression on the ADI-R can be accurate, they might only pick up "the tip of the iceberg," she noted.

The findings, based on a small sample, raise concerns about the use of the ADI-R and other retrospective measures in research, but do provide "some hope for early screening using parent report data," Dr. Miller pointed out. Such reports would be more feasible than neuroimaging, eye tracking, and other sophisticated testing that could be used over several well child visits, to detect declines and help determine which children should be further evaluated further or referred for interventions, she added. Phase III of the study is currently underway.

In other sibling studies, Dr. Saulnier discussed the use of eye-tracking testing in studies that prospectively followed high-risk infants whose siblings have been diagnosed with ASD and low-risk infants with typically developing siblings.

Under eye-tracking methodology, the child watches prerecorded movies on a monitor of women acting as caregivers, singing, and talking to an infant. It is well established that when viewing a social scene, typically developing adults focus on the eye region of the face, but those with autism look less at the eyes and significantly more at the mouth, body, and objects in the social scene. Those findings have been replicated in school-aged children, adolescents, and toddlers down to aged 2 years, she noted.

In infant studies, eye-tracking testing is performed at least 10 times from birth to age 3, with vocal recordings and clinical assessments at different periods.

Summarizing the findings, Dr. Saulnier said infants at low risk who have a typical outcome show a steady fixation of eye gaze from birth. But infants who are at high risk for ASD and "develop ASD by age 3 show a rapid decline in eye fixation between 2 and 6 months of age that is more predictive of ASD than any clinical measure."

Autism cannot be diagnosed with this test alone, she said. (Most of this work was conducted at the Yale Child Study Center, before she moved to Emory, she said.)

She provided examples of a 5-month-old low-risk infant, who developed typically and focused at the eye region of the face, contrasting with another 5-month old infant, who went on to develop autism by agd 3, who was not looking at the eye region of the face, focusing on the mouth, body, and objects.

Another example she showed was an infant who had normal results at 3 and 6 months, but by 9 months, the researchers started to see a shift, which she described as the "unfolding of autism." This child was diagnosed with autism at 12 months. She added, however, that it is rare to see that symptomatology so early and pronounced.

While it would be assumed that the children who go on to develop autism manifest the lack of eye fixation from birth, another finding from eye fixation studies is that the opposite is true, and "babies who went on to develop autism actually had significantly more eye fixation in the first 2 months of life," Dr. Saulnier said.

Typically developing infants maintain this focus on the eyes, "but whatever is happening in autism to make social monitoring not as salient, they’re trailing off, and you’re seeing this derailment in this eye fixation."

Other results of eye-tracking sibling studies might provide information about a window of opportunity – at about age 9-12 months – for an intervention "that could capitalize on the potential for resilience, she noted.

In infants whose older siblings have ASD and are either unaffected or have "shadow symptoms" of autism at age 3 years, eye-tracking results indicate that after reduced eye fixation, they exhibit a "course correction" in increased eye fixation that appears to start around 9 months of age.

Why this occurs is not understood, but this observation sheds some light on a possible window of time during which something could be done, before autism fully unfolds, such as coaching strategies for parents on keeping their child engaged "to produce a course correction if it wasn’t naturally going to occur," Dr. Saulnier said.

She and her associates are now conducting a randomized, controlled study of infants at risk at 12 months, evaluating a potential way to correct the course.

Among the goals in the future is to reduce the mean age of an autism diagnosis so that, once recognized, effective interventions can be started that could affect outcomes, she said. Although autism can be reliably diagnosed by 18-24 months, the mean age of ASD diagnosis is currently about 4.5 years, she noted.

Dr. Carter disclosed that she is one of the developers of the BITSEA screening tool, used in the study she presented. Dr. Saulnier had no disclosures; the studies she presented received support from the National Institute of Mental Health, the National Institute of Child Health and Human Development, the Marcus Foundation, and the Whitehead and Woodruff Foundations. Dr. Miller said the UCSD study has been funded by NIMH, Autism Speaks, and the MINDlist.

A tutorial on recognizing the early signs of ASD, developed by the Kennedy Krieger Institute, Baltimore,is available at https://www.youtube.com/watch?v=YtvP5A5OHpU.

[email protected]