Mayada Elsabbagh

Global prevalence of autism and other pervasive developmental disorders.

We provide a systematic review of epidemiological surveys of autistic disorder and pervasive developmental disorders (PDDs) worldwide. A secondary aim was to consider the possible impact of geographic, cultural/ethnic, and socioeconomic factors on prevalence estimates and on clinical presentation of PDD. Based on the evidence reviewed, the median of prevalence estimates of autism spectrum disorders was 62/10 000. While existing estimates are variable, the evidence reviewed does not support differences in PDD prevalence by geographic region nor of a strong impact of ethnic/cultural or socioeconomic factors. However, power to detect such effects is seriously limited in existing data sets, particularly in low‐income countries. While it is clear that prevalence estimates have increased over time and these vary in different neighboring and distant regions, these findings most likely represent broadening of the diagnostic concets, diagnostic switching from other developmental disabilities to PDD, service availability, and awareness of autistic spectrum disorders in both the lay and professional public. The lack of evidence from the majority of the worlds population suggests a critical need for further research and capacity building in low‐ and middle‐income countries. Autism Res 2012, 5: 160–179.

Getting answers from babies about autism

Because autism is rarely diagnosed before two years of age, little is known about its early symptoms and causes. In order to determine the earliest manifestations of the condition, recent interest has focused on infants at genetic risk for autism. Current evidence indicates that overt behavioural symptoms emerge around the end of the first year. However, studies using laboratory brain function measures have reported differences in groups of infants at-risk compared with low-risk controls during their first year. Some infants displaying such early differences, however, do not subsequently receive a diagnosis. As the search for early markers continues, infants at-risk present a persuasive model for gene by environment interactions leading to variable developmental pathways.

Neural Correlates of Eye Gaze Processing in the Infant Broader Autism Phenotype

BACKGROUND Studies of infant siblings of children diagnosed with autism have allowed for a prospective approach to study the emergence of autism in infancy and revealed early behavioral characteristics of the broader autism phenotype. In view of previous findings of atypical eye gaze processing in children and adults with autism, the aim of this study was to examine the early autism phenotype in infant siblings of children diagnosed with autism spectrum disorder (sib-ASD), focusing on the neural correlates of direct compared with averted gaze. METHODS A group of 19 sib-ASD was compared with 17 control infants with no family history of ASD (mean age=10 months) on their response to direct versus averted gaze in static stimuli. RESULTS Relative to the control group, the sib-ASD group showed prolonged latency of the occipital P400 event-related potentials component in response to direct gaze, but they did not differ in earlier components. Similarly, time-frequency analysis of high-frequency oscillatory activity in the gamma band showed group differences in response to direct gaze, where induced gamma activity was late and less persistent over the right temporal region in the sib-ASD group. CONCLUSION This study suggests that a broader autism phenotype, which includes an atypical response to direct gaze, is manifest early in infancy.

Disengagement of Visual Attention in Infancy is Associated with Emerging Autism in Toddlerhood

Background Early emerging characteristics of visual orienting have been associated with a wide range of typical and atypical developmental outcomes. In the current study, we examined the development of visual disengagement in infants at risk for autism. Methods We measured the efficiency of disengaging from a central visual stimulus to orient to a peripheral one in a cohort of 104 infants with and without familial risk for autism by virtue of having an older sibling with autism. Results At 7 months of age, disengagement was not robustly associated with later diagnostic outcomes. However, by 14 months, longer latencies to disengage in the subset of the risk group later diagnosed with autism was observed relative to other infants at risk and the low-risk control group. Moreover, between 7 months and 14 months, infants who were later diagnosed with autism at 36 months showed no consistent increases in the speed and flexibility of visual orienting. However, the latter developmental effect also characterized those infants who exhibited some form of developmental concerns (but not meeting criteria for autism) at 36 months. Conclusions Infants who develop autism or other developmental concerns show atypicality in the development of visual attention skills from the first year of life.

In Search of Biomarkers for Autism: Scientific, Social and Ethical Challenges

There is widespread hope that the discovery of valid biomarkers for autism will both reveal the causes of autism and enable earlier and more targeted methods for diagnosis and intervention. However, growing enthusiasm about recent advances in this area of autism research needs to be tempered by an awareness of the major scientific challenges and the important social and ethical concerns arising from the development of biomarkers and their clinical application. Collaborative approaches involving scientists and other stakeholders must combine the search for valid, clinically useful autism biomarkers with efforts to ensure that individuals with autism and their families are treated with respect and understanding.

Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder

We are performing whole-genome sequencing of families with autism spectrum disorder (ASD) to build a resource (MSSNG) for subcategorizing the phenotypes and underlying genetic factors involved. Here we report sequencing of 5,205 samples from families with ASD, accompanied by clinical information, creating a database accessible on a cloud platform and through a controlled-access internet portal. We found an average of 73.8 de novo single nucleotide variants and 12.6 de novo insertions and deletions or copy number variations per ASD subject. We identified 18 new candidate ASD-risk genes and found that participants bearing mutations in susceptibility genes had significantly lower adaptive ability (P = 6 × 10−4). In 294 of 2,620 (11.2%) of ASD cases, a molecular basis could be determined and 7.2% of these carried copy number variations and/or chromosomal abnormalities, emphasizing the importance of detecting all forms of genetic variation as diagnostic and therapeutic targets in ASD.

Quality of interaction between at-risk infants and caregiver at 12–15 months is associated with 3-year autism outcome

BACKGROUND   Recent models of the early emergence of autism spectrum disorder (ASD) propose that infant intrinsic risk susceptibilities in behaviour may be amplified by interaction within the early social environment into an increasingly atypical developmental trajectory. This study examines whether 6- and 12-month parent-infant interactions in at-risk siblings differ from those with low-risk and whether--in at-risk siblings--such interactions predict later 3-year classification of ASD or no ASD. METHOD   Within the British Autism Study of Infant Siblings (BASIS), 6-min videotaped episodes of parent-infant free play in infants at 6-10 months (45 at-risk siblings and 47 low-risk siblings) and 12-15 months (43 at-risk siblings and 48 low-risk siblings) in a laboratory setting were rated on the Manchester Assessment of Caregiver-Infant Interaction (MACI), blind to participant information. Standard tests were administered for concurrent behavioural signs of ASD features and developmental level. Systematic consensus diagnostic classification of ASD was made at 3 years for the at-risk siblings. RESULTS   Parent nondirectiveness and sensitive responsiveness differed in relation to ASD/risk status (at-risk ASD, at-risk no-ASD and low-risk) at both 6 and 12 months. At 6 months, infant liveliness was lower in the at-risk groups; at 12 months, infant attentiveness to parent and positive affect were lower in the at-risk group later diagnosed with ASD. Dyadic mutuality and intensity of engagement showed a group effect at 12 months. Dyadic mutuality, infant positive affect and infant attentiveness to parent at 12 months (but not 6 months) predicted 3-year ASD outcome, whereas infant ASD-related behavioural atypicality did not. CONCLUSIONS   This is the first prospective evidence that early dyadic interaction between at-risk infants and their parents is associated with later diagnostic outcome in ASD. Possible explanations for these findings and their theoretical implications are considered.

The development of face orienting mechanisms in infants at-risk for autism

Highlights ► Infants preferentially orient to socially relevant information such as faces. ► Infants at-risk for autism have a tendency to sustain attention to faces. ► Those infants who later develop autism show an equally strong face orienting response. ► Combined influence of social and attentional brain systems is implicated in autism.

Parent-infant interaction in infant siblings at risk of autism

Recent models of the early emergence of autism spectrum disorder (ASD) propose an interaction between risk susceptibility and the infants social environment, resulting in a progressively atypical developmental trajectory. The infants early social environmental experience consists mostly of interaction with caregivers, yet there has been little systematic study of early parent-infant interaction in infants at risk of ASD. This study examined the global characteristics of parent-infant interaction in 6- to 10-month-old infants with an older sibling diagnosed with ASD (at-risk sibs), in comparison with a group of infants with no family history of ASD (low-risk sibs). As part of the British Autism Study of Infant Siblings (BASIS), 6-min videotaped unstructured play interactions of mother-infant dyads (45 at-risk sibs and 47 low-risk sibs) were rated on global aspects of parent-infant interaction, blind to participant information. Differences in global characteristics of interaction were observed in both infant and parent contributions in the at-risk group compared to low-risk controls. In analyses adjusted for age and developmental level, at-risk sib infants were less lively, and their parents showed higher directiveness, and lower sensitive responding (as a trend after adjustment). Level of infant liveliness was independent of other interactive behaviour. Consistent with reports in previous literature in older children with autism and in other neurodevelopmental disorders, our findings may suggest that infants at genetic risk are exposed to a more directive interactive style relatively early in infancy. We discuss possible explanations for these findings and implications for further developmental study and intervention.

What you see is what you get: contextual modulation of face scanning in typical and atypical development

Infants’ visual scanning of social scenes is influenced by both exogenously and endogenously driven shifts of attention. We manipulate these factors by contrasting individual infants’ distribution of visual attention to the eyes relative to the mouth when viewing complex dynamic scenes with multiple communicative signals (e.g. peek-a-boo), relative to the same infant viewing simpler scenes where only single features move (moving eyes, mouth and hands). We explore the relationship between context-dependent scanning patterns and later social and communication outcomes in two groups of infants, with and without familial risk for autism. Our findings suggest that in complex scenes requiring more endogenous control of attention, increased scanning of the mouth region relative to the eyes at 7 months is associated with superior expressive language (EL) at 36 months. This relationship holds even after controlling for outcome group. In contrast, in simple scenes where only the mouth is moving, those infants, irrespective of their group membership, who direct their attention to the repetitive moving feature, i.e. the mouth, have poorer EL at 36 months. Taken together, our findings suggest that scanning of complex social scenes does not begin as strikingly different in those infants later diagnosed with autism.