Can family affectedness inform infant sibling outcomes of autism spectrum disorders

In recent years, the emergence of autism spectrum disorder (ASD) symptoms has been studied within the context of infant siblings (Rogers, 2009). Within infant sibling studies, a child born to a family raising one or more children with an ASD is followed longitudinally to examine, among other things, what aspects of early development help predict outcomes. This prospective longitudinal design provides a unique opportunity to study ASD symptoms as they develop and to identify the earliest possible markers of later ASD diagnoses. Previous infant sibling studies have assessed whether differences in visual fixation and disengagement (Zwaigenbaum, 2005), face processing (Young et al., 2009), early communication and joint attention behaviors (Landa & Garrett-Mayer, 2006), object exploration (Ozonoff et al., 2008), and head circumference (Elder, Dawson, Toth, Fein & Munson, 2008) can predict which infant siblings later develop an ASD. These studies have reliably found differences in a variety of early social and communication behaviors in infants who have older siblings with ASD. The present study moves beyond aspects of the infant’s development to examine whether features of family members may help inform which infants are at increased risk for ASD or other developmental concerns. Deficits in communication and reciprocal social behavior are not only core features of autism spectrum disorders but also are often present, to varying degrees, in other family members. Cross-sectional and family history studies have demonstrated that social and communication difficulties are more common in families with an ASD child than in families with only typically developing children (Bailey, Palferman, Heavey & Le Couteur, 1998; Ruser et al., 2007). These communication and relational differences are often studied as an element of the broader autism phenotype (BAP). The BAP is a constellation of subclinical behaviors associated with ASD that can be found in non-autistic family members. The BAP includes differences in social interactions, relationships, communication skills, and restricted patterns of behavior or intense interests. Previous reports detail higher rates of the BAP in fathers (Virkud et al., 2008) and siblings (Bailey et al., 1998; Constantino et al., 2006) of families with an ASD child, with the highest rates in multiplex families (Constantino et al., 2006; Virkud et al., 2008). The BAP is thought to be an index of family genetic risk for autism reflecting as yet undefined genetic factors (Piven, 2001). In infant sibling studies no specific genetic mechanisms have been identified; therefore, the present study does not examine genetic pathways but rather assesses the social and communication features of the BAP that are presumed to index genetic risk. Previous studies posit that the social-communicative differences of the BAP are normally distributed across the general population and are genetically transmitted across generations (Constantino et al., 2003; Constantino & Todd, 2003; Virkud et al., 2008). The gradient of social-communication differences associated with the BAP have also been labeled quantitative autistic traits (QAT; Virkud et al., 2008). The Social Responsiveness Scale (SRS) is a widely used instrument that measures both typical features of autism and subclinical communication and relationship differences that may be seen among relatives. The SRS is particularly well-suited for the present study because it is well validated in family members of typically developing children and children with ASD (Constantino et al., 2006, 2007) and previous studies have documented the heritability of the reciprocal and social communication behaviors captured by the SRS (Constantino & Todd, 2005; Hoekstra, Bartels, Verweij & Boomsma, 2007). Family affectedness may be conceptualized in several ways. When assessing the affectedness of siblings, diagnostic categories are often employed (i.e., ASD or non-ASD). Then affected families can be categorized on the basis of the number of children diagnosed with an ASD, resulting in simplex and multiplex groups. This approach has direct clinical relevance but does not capture the varying degrees of affectedness and subclinical difficulties that may be present in both siblings and parents. Therefore, the present study examined family affectedness in two ways: by assigning families to a risk group (i.e., simplex, multiplex or typical) on the basis of the older sibling(s)’ diagnostic status and by assessing varying degrees of QAT, as measured by the SRS, in parents and siblings. The present prospective longitudinal study attempts to replicate differential levels of family affectedness (or QAT) in families with at least one child diagnosed with an ASD versus families with only typically developing children, something previously reported only in cross-sectional and family history studies (Bailey et al., 1998; Constantino et al., 2006, 2007). Additionally, this study aims to move the field forward by investigating QAT as a predictor of developmental outcomes in infant siblings.