If autism emerges early on, why has research with infants and toddlers arrived so late?
Over the past decade, there has been remarkable progress in our understanding of the early development of children with autism. Before the 1990s, it was rare for children to receive a diagnosis of autism until three or four years of age, and in many cases considerably later. Consequently, much of the historical literature on autism starts with descriptions of children aged four to five years or older. This is despite the fact that, in most cases, autism has an onset in infancy and is the result of genetic and other factors that affect very early brain development.
However, progress has recently been made in the earlier identification of children with autism and many children are now first identified in the pre-school period. Motivating these efforts to improve earlier identification is the recognition that earlier-delivered intervention may improve outcomes and prevent secondary neurodevelopmental disturbances.
This improvement in earlier recognition has been informed by, and in part driven by, findings from a number of strands of research that have afforded us, for the first time, a picture of the emergence of autism – “a new science of autism in infancy” (Charman, 2010).
Infants at high-risk of autism
The research areas that have underpinned our understanding of autism in infancy include, studying home movies of infants who later go on to receive a diagnosis of autism, the development of prospective screening instruments to identify possible cases of autism from the first few years of life, and the use of the genetic “high-risk” research design of studying younger siblings of children with a diagnosis of autism from the first year of life (Rogers, 2009; Yirmiya & Charman, 2010). Although some form of autism affects around one per cent of children and young people, due to its (in part) genetic underpinnings, children born subsequent to a child who goes on to receive a diagnosis are at increased risk of going on to develop autism themselves. In recent studies, the recurrence rate of autism in families has been reported as ten per cent or even higher (Constantino, Zhang, Frazier, Abbacchi & Law, 2010; Ozonoff et al., 2011). This has meant that, for the first time, it is practicable and feasible to study high-risk children from infancy.
Over the past decade, a number of groups worldwide have initiated truly prospective observational studies by exploiting this higher within-family recurrence. This allows the possibility to recruit a cohort of younger infant siblings of an older child with an autism diagnosis and to follow their development over time, and to determine whether characteristics measured in infancy differentiate the children in the cohort who will go on to develop autism versus those who do not. Commonly, infant siblings are seen from as young as six months of age or even earlier, and then followed up several times over the infant and toddler years until the age of two or three years, when it becomes possible for expert teams to make a clinical diagnosis. The design also allows one to test differences between the high-risk sibling group and low-risk controls with no family history of autism, which some groups have called a “broader autism phenotype” (BAP) analysis, meaning that there may be characteristics that run in families of children with autism that are subclinical in severity but are shared by different family members.
The picture emerging from these studies is that there are a number of identifiable differences, mostly in early social communication behaviours (for example, response to name or social smiling) but also, in some studies, difficulties in attention control and even motor development. However, perhaps to the surprise of the researchers who set up such studies, to date, in most studies, differences have emerged around the infant siblings’ first birthday and into the second year of life – very few studies have found clear predictors as early as six months of age.
Understanding early communication behaviours
A landmark study published last year (Ozonoff et al., 2010) was the first to report on a sample as large as 25 siblings who went on to receive an autism spectrum diagnosis at 36 months. It compared rates of three early social communication behaviours (gaze to faces, social smiles and directed vocalisations) captured by observers during assessment sessions when the siblings were six, 12, 18, 24 and 36 months of age. They found a slowing of development in terms of raw scores on a general developmental assessment – that is, the high-risk siblings begin to fall behind the low-risk controls. In contrast, there was an actual decline in the rates of the early social communication behaviours (a real reduction in frequency of social responses). This loss began around the first birthday and continued across the second year of life, and on some measures into the third year. This pattern of loss of skills was found in over three-quarters of the high-risk group. However, at age six months, there were no differences between the groups, indicating that the high-risk siblings who went on to meet diagnostic criteria at 36 months of age showed the same rates of early social communication behaviours as controls.
The second notable, and perhaps surprising, finding was that by parental report, looking back from the timepoint of the 36 month interview, loss of skills was reported for only a minority of those children whose social communication skills declined over the second year of life (at least when interacting in an unfamiliar setting with an unfamiliar adult in the observations taken in the lab). This is surprising in part because families taking part in these high-risk sibling studies understand the familial nature of the design and we might expect worried parents to be hypervigilent for early signs that something is not right with their younger child.
An additional report by the same group illustrates another surprising finding that has emerged from the high-risk studies: it is not necessarily the case that social interactions in the first year of life, even when measured very carefully in laboratory studies, reveal which children will go on to have autism. Young, Merin, Rogers and Ozonoff (2009) conducted the classic “still face” paradigm with six-month-old high-risk infants in which, after a period of natural mother-child interaction, mothers are prompted to “freeze”. Most typically-developing infants become distressed very quickly in this situation. Using a combination of behavioural and eye-tracking measures, the study found that responses to the mothers “still face” were not associated with preliminary autism outcomes at 24 months of age – indeed, responses of those infants who went on to receive an autism diagnosis showed the usual “distress” pattern to the change in their caregiver’s interactive behaviour.
The British Autism Study of Infant Siblings (BASIS) is a collaborative research network for the study of infants at risk of autism in the UK. Its primary aim is to facilitate collaborative links between scientists working in the area. Using newly developed techniques for studying brain and behaviour in infants, BASIS scientists investigate whether there are any differences in development between infants who have brothers or sisters with autism and those who do not. BASIS families are seen at the Centre for Brain and Cognitive Development, also known as “the babylab”, directed by Professor Mark Johnson.
In addition to behavioural studies, several groups have begun to use novel experimental technology to study autism in infants, such as eye tracking (computers that automatically detect where on a computer screen an infant is looking) and brain imaging measures, such as evoked response potentials (ERPs), magnetic resonance imaging (MRI), and near infra-red spectroscopy (NIRS). These techniques aim to test if there may be disrupted neural processing of both social and non-social stimuli in high-risk siblings (Elsabbagh et al., 2009).
In a recent study with nine-month-olds we found that the well-recognised “neural signal” that responds to direct (versus averted) eye gaze was different in the at-risk infant siblings than in the low-risk controls. We have since been following the siblings up until their third birthday to see whether such differences distinguish those at-risk siblings who go on to have an autism diagnosis. The repeated nature of these longitudinal studies (in our most recent study we see the siblings at four, eight, 14, 24 and 36 months of age) holds out the promise to unravel developmental effects to help us understand more about the fundamental underlying nature of atypical development in autism as it emerges.
The study of high-risk siblings promises to help us understand the developmental mechanisms that underlie the emergence of autism in the first few years of life, although, to date, clear very early indicators of an ASD outcome have not been as easy to identify as many people expected. In the long term, this will help identify the early signs of the disorder, allowing for earlier and more effective intervention aimed at improving the quality of life of children with autism and their families.
Professor Tony Charman has served on a number of expert panels for the UK Medical Research Council, the National Institute of Health and Clinical Excellence (NICE), and the US National Institutes of Health. He is a member of the Advisory Group to the All Party Parliamentary Group on Autism and is currently based at the Centre for Research in Autism and Education (CRAE), Institute of Education, University of London:
Charman, T. (2010). Autism research comes of (a young) age. Journal of the American Academy of Child and Adolescent Psychiatry, 49, 208-209.
Charman, T. (2011). Glass half full or half empty? Testing social communication interventions for young children with autism. Journal of Child Psychology and Psychiatry, 52, 22-23.
Constantino, J. N., Zhang, Y., Frazier, T., Abbacchi, A. M., & Law, P. (2010). Sibling recurrence and the genetic epidemiology of autism. American Journal of Psychiatry, 167, 1349-1356.
Elsabbagh, M., Volein, A., Csibra, G., Holmboe, K., Garwood, H., Tucker, L., et al. (2009). Neural correlates of eye gaze processing in the infant broader autism phenotype. Biological Psychiatry, 65, 31-38.
Ozonoff, S., Iosif, A. M., Baguio, F., Cook, I. C., Hill, M. M., Hutman, T., et al. (2010). A prospective study of the emergence of early behavioral signs of autism. Journal of the American Academy of Child and Adolescent Psychiatry, 49, 256-266.
Ozonoff, S., Young, G., Carter, A. S, Messinger, D., Yirmiya, N., Zwaigenbaum, L., et al. (2011). Recurrence risk for autism spectrum disorder: A Baby Siblings Research Consortium Study. Pediatrics, in press.
Rogers, S. (2009). What are infant siblings teaching us about autism in infancy? Autism Research, 2, 125-137.
Yirmiya, N., & Charman, T. (2010). The prodrome of autism: early behavioral and biological signs, regression, peri- and post-natal development and genetics. Journal of Child Psychology and Psychiatry, 51, 432-458.
Young, G., Merin, N., Rogers, S., & Ozonoff, S. (2009). Gaze behavior and affect at 6-months: predicting clinical outcomes and language development in typically developing infants and infants at-risk for autism. Developmental Science,12, 798-814.