Likely the greatest excitement in the past five years in research on autism spectrum disorders (ASD) has originated from molecular genetic studies (Varki, Geschwind, & Eichler, 2008), which have yielded an unprecedented number of important discoveries (e.g., Morrow et al., 2008; Sebat et al., 2007; Wang et al., 2009; Weiss et al., 2008). To leverage these discoveries in pursuit of causes of this vastly heterogeneous syndrome (Volkmar, Lord, Bailey, Schultz, & Klin, 2004), there is a need for successful systems biology approaches, leading the field from gene to cellular function to neuronal circuitries implicated in pathogenesis (Abrahams & Geshwind, 2008). With this ultimate goal in mind, our lab has researched, for the past eight years, developmentally early-emerging and evolutionarily highly conserved mechanisms of adaptive social action (e.g., Jones, Carr, & Klin, 2008; Klin, Jones, Schultz, Volkmar, & Cohen, 2002a, 2002b; Klin, Jones, Schultz, & Volkmar, 2003; Klin, Lin, Gorrindo, Ramsay, & Jones, 2009). For human infants, a central task of social adaptation is engagement with caregivers. Given their fragility at birth, success on this task is of immediate survival value and of fundamental evolutionary significance. For example, a central skill facilitating adaptive success on this task is preferential attention to

biological motion, which can be interpreted as a form of perceptual life detector (Johnson, 2006). Typically developing human infants exhibit this behavior within the first days of life (Simion, Regolin, & Bulf, 2008). It is highly conserved across species (Blake, 1993; Regolin, Tommasi, & Vallortigara, 2000) because it is critical for filial attachment and detection of predators (Johnson, 2006). In human infants, it facilitates perception of social signals and is a precursor to the capacity for attributing mental states to others (Frith & Frith, 1999). In a recent paper (Klin et al., 2009), we showed that this mechanism is fundamentally altered in two-year-olds with autism: They fail to preferentially orient to pointlight displays of biological motion, attending instead to physical, not social, contingencies that are disregarded by controls-specifically, audiovisual synchronies between point lights and sounds. The relevance of this finding to elucidating core disabilities in autism was shown in a parallel study (Jones et al., 2008) in which we found that two-year-olds with autism show diminished preferential attention to the eyes of others, attending instead to the mouths of approaching adults. This presents a stark contrast to typical development: Newborns can distinguish a face looking towards them from a face looking away (Farroni, Csibra, Simion, & Johnson, 2002), and by three months, infants look more at a person’s eyes than at other parts of the face (Haith, Bergman, & Moore, 1977). Taking these two studies together, we hypothesized that the toddlers with autism may have preferentially attended to mouths because, in the human face, this is the greatest source of audiovisual synchrony as lip motions occur synchronously with speech sounds (Jones & Klin, 2009; Klin et al., 2009). A wide range of foundational normative pro cesses of socialization, including mutual gaze, gaze following, joint attention, and even language acquisition, are predicated on spontaneous searching for the eyes of others and increasing responsiveness to the gaze signals contained therein (Klin et al., 2002b). These are all core disabilities of the ASD phenotype (Volkmar et al., 2004). In this chapter, we provide a description of some of our key studies to date involving infants and toddlers with ASD and summarize their potential utility in addressing two important grand challenges in autism research. First, given the vast etiologic heterogeneity (e.g., the multiplicity of implicated genetic processes), how can we account for the phenotypic homogeneity? Second, given the current unsatisfactory status of animal modeling in autism research, how can we utilize developmental psychopathology insights to hone in on more promising assays in developmental neurobiology research? This discussion is preceded by a brief summary of our developmental framework in approaching research of the pathogenesis of autism and related disorders.