Leslie J. Carver

Recurrence risk for autism spectrum disorders: A baby siblings research consortium study

OBJECTIVE: The recurrence risk of autism spectrum disorders (ASD) is estimated to be between 3% and 10%, but previous research was limited by small sample sizes and biases related to ascertainment, reporting, and stoppage factors. This study used prospective methods to obtain an updated estimate of sibling recurrence risk for ASD. METHODS: A prospective longitudinal study of infants at risk for ASD was conducted by a multisite international network, the Baby Siblings Research Consortium. Infants (n = 664) with an older biological sibling with ASD were followed from early in life to 36 months, when they were classified as having or not having ASD. An ASD classification required surpassing the cutoff of the Autism Diagnostic Observation Schedule and receiving a clinical diagnosis from an expert clinician. RESULTS: A total of 18.7% of the infants developed ASD. Infant gender and the presence of >1 older affected sibling were significant predictors of ASD outcome, and there was an almost threefold increase in risk for male subjects and an additional twofold increase in risk if there was >1 older affected sibling. The age of the infant at study enrollment, the gender and functioning level of the infants older sibling, and other demographic factors did not predict ASD outcome. CONCLUSIONS: The sibling recurrence rate of ASD is higher than suggested by previous estimates. The size of the current sample and prospective nature of data collection minimized many limitations of previous studies of sibling recurrence. Clinical implications, including genetic counseling, are discussed.

Neural correlates of face and object recognition in young children with autism spectrum disorder, developmental delay, and typical development

This study utilized electroencephalographic recordings to examine whether young children with autism spectrum disorder (ASD) have impaired face recognition ability. High-density brain event-related potentials (ERPs) were recorded to photos of the childs mothers face versus an unfamiliar female face and photos of a favorite versus an unfamiliar toy from children with ASD, children with typical development, and children with developmental delay, all 3 to 4 years of age (N = 118). Typically developing children showed ERP amplitude differences in two components, P400 and Nc, to a familiar versus an unfamiliar face, and to a familiar versus an unfamiliar object. In contrast, children with ASD failed to show differences in ERPs to a familiar versus an unfamiliar face, but they did show P400 and Nc amplitude differences to a familiar versus an unfamiliar object. Developmentally delayed children showed significant ERP amplitude differences for the positive slow wave for both faces and objects. These data suggest that autism is associated with face recognition impairment that is manifest early in life.

Clinical Assessment and Management of Toddlers With Suspected Autism Spectrum Disorder: Insights From Studies of High-Risk Infants

With increased public awareness of the early signs and recent American Academy of Pediatrics recommendations that all 18- and 24-month-olds be screened for autism spectrum disorders, there is an increasing need for diagnostic assessment of very young children. However, unique challenges exist in applying current diagnostic guidelines for autism spectrum disorders to children under the age of 2 years. In this article, we address challenges related to early detection, diagnosis, and treatment of autism spectrum disorders in this age group. We provide a comprehensive review of findings from recent studies on the early development of children with autism spectrum disorders, summarizing current knowledge on early signs of autism spectrum disorders, the screening properties of early detection tools, and current best practice for diagnostic assessment of autism spectrum disorders before 2 years of age. We also outline principles of effective intervention for children under the age of 2 with suspected/confirmed autism spectrum disorders. It is hoped that ongoing studies will provide an even stronger foundation for evidence-based diagnostic and intervention approaches for this critically important age group.

Developments in Long-Term Explicit Memory Late in the First Year of Life Behavioral and Electrophysiological Indices

Coincident with developments in the temporal-cortical explicit memory network, long-term recall abilities are newly emergent late in the first year of human life. We recorded event-related potentials (ERPs) in 9-month-olds as an index of the integrity of the neural substrate underlying a task thought to reflect explicit memory, namely, deferred imitation. ERP measures of recognition memory 1 week after unique laboratory experiences predicted whether and how much infants recalled of the experiences 1 month later. The findings further imply that memory storage and consolidation processes are a major source of variability in long-term recall memory late in the first year of life.

Atypical face versus object processing and hemispheric asymmetries in 10-month-old infants at risk for autism.

BACKGROUND Previous studies have documented atypicalities in face/object processing in children and adults with autism spectrum disorders (ASDs). To investigate whether such atypicalities may reflect a genetically mediated risk factor present early in development, we measured face/object processing in 10-month-old high-risk infants who carry some of the genes associated with ASD because they have an older sibling diagnosed with the disorder. METHODS We employed event-related potentials (ERPs) to measure cortical responses to pictures of faces and objects, the objects being toys. Latencies and amplitudes of four ERP components (P100, N290, P400, and Nc) were compared between 20 high-risk infants and 20 low-risk control subjects (infants with no family history of ASD). RESULTS Responses to faces versus objects differed between high- and low-risk infants for the latencies of the N290 and P400. Differences were driven by faster responses to faces than objects in low-risk, but not high-risk, infants (P400) and, conversely, faster responses to objects than faces in high-risk, but not low-risk, infants (N290). Object responses were also faster in high-risk than low-risk infants (both N290 and P400). Left versus right hemisphere responses also differed between high- and low-risk infants for the amplitudes of the P100, N290, and P400; collapsed across faces/objects, low-risk, but not high-risk, infants exhibited hemisphere asymmetries. CONCLUSIONS Genetic risk for ASD is associated with atypical face versus object processing and an atypical lack of hemispheric asymmetry early in life. These atypicalities might contribute to development of the disorder.

Electrophysiological indexes of encoding and behavioral indexes of recall: examining relations and developmental change late in the first year of life.

Long-term memory undergoes pronounced development in the latter part of the 1st year. This reasearch combines electrophysiological (event-related potential [ERP]) and behavioral (deferred imitation) measures of encoding and recall, respectively, in an examination of age-related changes in and relations between encoding and recall during this time. In a short-term longitudinal study, infants were exposed to different multistep sequences at 9 and at 10 months. In both phases, they were tested for immediate recognition of the events via ERPs (as an index of encoding), and for recall of them 1 month later. At both ages, infants encoded the events; encoding was more robust at 10 months than at 9 months. After the 1-month delay, infants failed to recall the events experienced at 9 months, but evidenced recall of the events experienced at 10 months. In spite of developmental differences in encoding and recall over this period, indexes of encoding at 9 months were correlated with measures of recall of events experienced at 10 months and tested 1 month later.

Atypical Social Referencing in Infant Siblings of Children with Autism Spectrum Disorders

Social referencing was investigated in 18-month-old siblings of children with autism spectrum disorders (ASD; “high-risk infants”). Infants were exposed to novel toys, which were emotionally tagged via adults’ facial and vocal signals. Infants’ information seeking (initiation of joint attention with an adult) and their approach/withdrawal behavior toward the toys before versus after the adults’ emotional signals was measured. Compared to both typically developing infants and high-risk infants without ASD, infants later diagnosed with ASD engaged in slower information seeking, suggesting that this aspect of referencing may be an early indicator of ASD. High-risk infants, both those who were and those who were not later diagnosed with ASD, exhibited impairments in regulating their behavior based on the adults’ emotional signals, suggesting that this aspect of social referencing may reflect an endophenotype for ASD.

Reward sensitivity to faces versus objects in children: an ERP study

How children respond to social and nonsocial rewards has important implications for understanding social cognitive development. Adults find faces intrinsically rewarding. However, little is known about how children respond to face vs nonface rewards. We utilized event-related potentials (the stimulus-preceding negativity, SPN) to measure differences in reward anticipation during a guessing game in 6- to 8-year-olds. Children were presented with reward indicators accompanied by incidental face or nonface stimuli. Nonface stimuli were comprised of scrambled faces in the shape of arrows, controlling for low-level properties of the two conditions. Children showed an increased SPN when the reward stimuli were accompanied by faces, relative to nonface stimuli. This suggests that children find a face stimulus more rewarding than a nonface stimulus. The results have important implications for processing social vs nonsocial rewards in typically developing children, and allow testing of populations with deficits in social reward processing, such as autism spectrum disorder.

Non-ASD outcomes at 36 months in siblings at familial risk for autism spectrum disorder (ASD): A baby siblings research consortium (BSRC) study

We characterized developmental outcomes of a large sample of siblings at familial high‐risk of autism spectrum disorder (ASD), who themselves did not have ASD (n = 859), and low‐risk controls with no family history of ASD (n = 473). We report outcomes at age 3 years using the Mullen Scales of Early Learning, the Autism Diagnostic Observation Schedule (ADOS), the Autism Diagnostic Interview—Revised (ADI‐R) and adaptive functioning on the Vineland Adaptive Behavior Scales. Around 11% of high‐risk siblings had mild‐to‐moderate levels of developmental delay, a rate higher than the low‐risk controls. The groups did not differ in the proportion of toddlers with mild‐to‐moderate language delay. Thirty percent of high‐risk siblings had elevated scores on the ADOS, double the rate seen in the low‐risk controls. High‐risk siblings also had higher parent reported levels of ASD symptoms on the ADI‐R and lower adaptive functioning on the Vineland. Males were more likely to show higher levels of ASD symptoms and lower levels of developmental ability and adaptive behavior than females across most measures but not mild‐to‐moderate language delay. Lower maternal education was associated with lower developmental and adaptive behavior outcomes. These findings are evidence for early emerging characteristics related to the “broader autism phenotype” (BAP) previously described in older family members of individuals with ASD. There is a need for ongoing clinical monitoring of high‐risk siblings who do not have an ASD by age 3 years, as well as continued follow‐up into school age to determine their developmental and behavioral outcomes. Autism Res 2017, 10: 169–178.

Non-ASD outcomes at 36 months in siblings at familial risk for autism spectrum disorder (ASD)

We characterized developmental outcomes of a large sample of siblings at familial high‐risk of autism spectrum disorder (ASD), who themselves did not have ASD (n = 859), and low‐risk controls with no family history of ASD (n = 473). We report outcomes at age 3 years using the Mullen Scales of Early Learning, the Autism Diagnostic Observation Schedule (ADOS), the Autism Diagnostic Interview—Revised (ADI‐R) and adaptive functioning on the Vineland Adaptive Behavior Scales. Around 11% of high‐risk siblings had mild‐to‐moderate levels of developmental delay, a rate higher than the low‐risk controls. The groups did not differ in the proportion of toddlers with mild‐to‐moderate language delay. Thirty percent of high‐risk siblings had elevated scores on the ADOS, double the rate seen in the low‐risk controls. High‐risk siblings also had higher parent reported levels of ASD symptoms on the ADI‐R and lower adaptive functioning on the Vineland. Males were more likely to show higher levels of ASD symptoms and lower levels of developmental ability and adaptive behavior than females across most measures but not mild‐to‐moderate language delay. Lower maternal education was associated with lower developmental and adaptive behavior outcomes. These findings are evidence for early emerging characteristics related to the “broader autism phenotype” (BAP) previously described in older family members of individuals with ASD. There is a need for ongoing clinical monitoring of high‐risk siblings who do not have an ASD by age 3 years, as well as continued follow‐up into school age to determine their developmental and behavioral outcomes. Autism Res 2017, 10: 169–178.