By 12 months, however, there are significant differences in the infants who go on to develop ASD, hinting at a fundamental change in social communication as well as other behaviors taking place between 6 and 12 months. What are some of the behaviors that have been identified at 12 months? A small number of children begin to show slight delays in fine or gross motor development at this age, though for most children this is a pattern that emerges later during the second year of life (Landa & Garrett-Mayer, 2006). Within the motor domain, some children show unusual repetitive behaviors that involve atypical arm waving movements (Iverson & Wozniak, 2007; Loh et al., 2007). Differences in visual attention are also risk signs for ASD. One example is atypical looking at objects, such as looking at objects from the corner of one’s eyes or staring for an unusually long time at simple objects (Ozonoff et al., 2008). Other attentional problems include difficulty disengaging attention from one visual stimulus and shifting attention toward a novel stimulus (Zwaigenbaum et al., 2005). In addition to these motor and visual behaviors, more direct signs of social-communication impairment are also found at 12 months. These infants show reduced eye contact, social smiling, social interest, imitation, reduced responding to bids for joint attention, as well as reduced responding to their own name (Nadig et al., 2007; Ozonoff et al., 2010; Presmanes et al., 2007; Zwaigenbaum et al., 2005). It appears that these differences in joint attention and response to name reflect social interest and motivation (and not more basic visual or attention deficits) in that they correlate most closely with other behaviors related to initiating social engagement with other people (Rogers, 2009). Finally, even at 12 months delays are already evident in both nonverbal gestural communication and in language. Infants who later develop ASD are less likely to intentionally communicate with others using either pointing or other social gestures (Mitchell et al., 2006).

Importantly, no single atypical behavior has been found that is shared by all 12 month olds who later go on to meet criteria for ASD. Instead, as with the diagnosis of ASD itself, there is a constellation of social, attentional and motor behaviors that may be considered risk markers (Zwaigenbaum et al., 2005). If a baby exhibits several of these behaviors at 12 months, specifically, 7 or more risk markers, they are more likely to meet diagnostic criteria for ASD at a later age (Zwaigenbaum et al., 2005). In this way studies of infants at risk reflect the complex nature of the disorder. ASD is complex (heterogeneous) in terms of its genetic basis, range of behaviors and severity of phenotypic expression, and now has been shown to be complex with respect to the range of phenotypic risk markers. Current genetic studies suggest that the majority of ASD cases may be explained by a large number of variable genetic risk factors, each variant conferring small risk. On this model, ASD likely requires multiple risk genes that interact with each other and the environment (Abrahams & Geschwind, 2008). There is also growing evidence that between 10% and 20% of ASD cases may be explained by unusual chromosomal rearrangements, mutations in specific ASD genes, or copy number variants (deletions or duplications), often arising de novo and presenting as more severe cases accompanied by intellectual disability. Among infants at risk, occasionally a young infant (below the age of 12 months) already shows atypical behaviors, usually sensory or motor patterns, although as noted, this is not found in the majority of infants (cf. Bryson et al., 2007). These infants invariably go on to have more severe ASD symptoms as well as intellectual disability. One possibility is that these infants who show very early signs may also have unusual copy number variants or other submicroscopic chromosomal anomalies, which would be consistent with their phenotype.

Elsabbagh and colleagues (Elsabbagh et al., 2009a) followed up on earlier studies showing atypical attention at 12 months using reaction times in looking behavior during an experimental task. They compared high and low risk infants at 9-10 months of age on an attention disengagement paradigm. The high risk infants took longer to disengage from a central stimulus and, unlike the low risk infants, did not find it easier to disengage when a 200 millisecond gap was inserted between the initial central stimulus and the peripheral distracter. Another study investigated working memory for social and non-social stimuli in infants at 6 and 9 months of age (Noland et al., 2010). The main findings were that performance on the social stimuli was the same in the high and low risk groups, however, the high risk group performed significantly better on the non-social stimuli. These findings are especially interesting as they suggest that the endophenotype may have more to do with differences in the processing of objects rather than people. Moreover, studies of atypical attention (Elsabbagh et al., 2009a; Ozonoff et al., 2008; Zwaigenbaum et al., 2005) generally use non-social stimuli so stickier attention or unusual looking behaviors may be the result of enhanced interest in objects, which could later be reflected in superior perceptual and attention performance in older children and adults with ASD (Mottron, Dawson, & Soulieres, 2009).

Electrophysiological (EEG) studies have investigated neural responses to faces in 10 month old infants. Elsabbagh and colleagues (Elsabbagh et al., 2009b) measured event-related potentials (ERP) to female faces with direct or averted gaze. The early components of the face responsive ERP (PI and N290) were the same in the high and low risk infants. In contrast, the P400, a later component that is sensitive to top down visual processes perhaps related to computing the communicative or affective significance of eye gaze, had a significant longer latency for direct gaze among the high risk infants. These infants also show increased oscillatory activity in the gamma band at baseline and during the task over central and temporal brain regions using time frequency analysis, which is taken as a possible marker of atypical neural connectivity. The findings suggest that although the neural mechanisms underlying face processing are not impaired in infants at risk, they do show differences related to neural processing of eye gaze direction, and their brains may also have altered connectivity, as has been found in older children with ASD using EEG (Murias, Webb, Greenson & Dawson, 2007) and other methods (see Belmonte et al., 2004). Another ERP study also explored face processing in 10 month old infants at risk (McCleery et al., 2009). In this study McCleery and his colleagues analyzed infants’ N290 and P400 responses to familiar and unfamiliar faces and objects. Their main findings were that the high risk infants showed faster N290 and P400 responses to objects, but there were no group differences in latency of responses to faces. Instead, they found that the high risk infants showed reduced hemispheric asymmetry in ERP responses, suggesting that lateralization of brain organization for face processing may fail to develop during the first year of life in infants at risk. In a recent study of speech processing in infants at risk, a similar pattern of failure to develop functional lateralization for language in 9 and 12 month-olds was also found (Seery et al., 2010). It is interesting to note that differences in brain organization and connectivity in high risk infants emerge in the same period when accelerated head growth has been found in children with autism (Redcay & Courchesne, 2005).

Behavioral studies have also compared high and low risk groups of infants and while most have not found differences, a few findings have been reported in the literature (Rogers, 2009). Nadig et al. (2007) found that compared to low risk infants high risk infants showed less preference for infant-directed speech relative to adult-directed speech, though there was wide variability in preferences found in both groups. The still-face paradigm, which involves dyadic interaction between babies and their mothers who alternate between engaged interaction and neutral disengaged segments, has been used in several studies with 4-6 month old infants. Yirmiya and her colleagues (Yirmiya et al., 2006) reported that at 4 months, high risk infants (none of whom later received an ASD diagnosis) were slightly less synchronous in their interactions with their mothers and more likely to show neutral affect. Cassel et al. (2007) reported less smiling during the face-to-face interaction in high risk 6 month olds. And Merin et al. (2007) found that 6 month old high risk infants were more likely than low risk infants to look more at their mothers’ mouth than her eyes during the interaction phases. Interestingly, Young et al. (2009) followed up the high risk infants in this latter study through to outcome and found that not one of the high risk infants who preferred to look at the mouth was later diagnosed with ASD. Instead, preference for looking at the mouth at 6 months predicted higher expressive language scores at age 2. These findings suggest that there may be subtle differences in the social-affective behavior of infants at risk for ASD but that these behaviors are not predictive of later outcomes.

It used to be thought that regression, defined as a period of normal development followed by a significant change in which there is a loss of previously acquired language and other skills, was a pattern associated with about a quarter of the ASD population (Luyster et al., 2005). Studies of infants at risk suggest that regression, defined specifically in terms of a gradual loss of social communication skills, may be characteristic of all children with ASD (Ozonoff et al., 2010). There is some evidence to suggest that this definition of ASD may distinguish this complex neurodevelopmental disorder from others with which it is closely associated, including specific language impairment (Pickles et al., 2009). On this view, infants who once were interested in people, looked at their eyes and faces, followed eye gaze, and initiated and responded to social interactions, gradually lose these skills in the period between around 9 and 24 months. The onset, timing, and severity of the loss varies widely across children (Ozonoff et al., 2010) and it is likely that some children who experience these losses and meet criteria for an ASD diagnosis during the preschool years, later regain the skills and appear to have ‘recovered’ - almost always in the context of intensive behavioral interventions (Sutera et al., 2007).

Studies of infants at risk have provided us with a fundamentally new view of ASD, and in particular the onset of the social and communicative impairments. But there is still a great deal that we do not know. Gradual loss of connection with the social world begins in the latter half of the first year of life. This is a period of significant cognitive change that is seen across development. Within the social domain perceptual expertise for speech and faces emerges as a result of experience-dependent learning; infants form attachments to their primary caregiver and become wary of strangers; joint attention and intentional communication skills emerge. The infant, who is now mobile and independent, becomes more actively engaged with the environment and learning from the surrounding culture (see Meltzoff et al., 2009). These advances all take place in the context of a rapidly changing brain (Kagan, 2008). But what precipitates the different developmental path taken by infants with ASD? What critical neural mechanisms underlie the differences? Is ASD driven by the loss of motivation to engage in the social world, or is it more related to greater engagement in the world of objects? Whatever the answers may turn out to be, prospective studies of social cognition and social behavior in infants at risk for ASD will provide important clues to the mechanisms that drive developmental changes in this domain in all infants.