Infant siblings and the investigation of autism risk factors

In 1957, Pearson and Kley published a prescient paper asserting that neuropsychiatric research should capitalize on the "tendency of particular abnormalities of behavior to run in families" (p. 406) so that "subpopulations defined in terms of genetic relationship to index cases...might be studied longitudinally..." (p. 418) [1]. They went on to note that such studies could be effective and economical for etiologic research. A 1976 review of the genetics of infantile autism and childhood schizophrenia [2] highlighted the potential of Pearson and Kley's high-risk design for etiologic research, but at that time the only such studies underway were investigations focusing on children of parents with schizophrenia (reviewed by Garmezy [3]). In the 1980s, prompted by the 1977 publication of Folstein and Rutter's seminal autism twin study [4], siblings of autism probands increasingly were included in research samples; however, these were largely cross-sectional family studies in which researchers looked at recurrence risk and genetic segregation or linkage, not at prospective investigations where at-risk siblings were the subjects of principal interest. The first consideration of the prospective infant sibling study in autism, according to Yirmiya and Ozonoff, occurred in the mid-1980s, when US and UK researchers contemplated but rejected the idea because of concerns over heterogeneity in index proband diagnosis [5]. Once standard diagnostic tools were developed in the early 1990s, these projects moved forward with a focus firmly on phenotypic antecedents and very early signs of autism spectrum disorders (ASDs). Rogers [6] has since described the discovery of "the first behavioral characteristics that predict development of autism" as the "Holy Grail" (p. 126) of autism infant siblings research. Today there are 25 infant sibling research teams that are part of the High Risk Baby Siblings Research Consortium (BSRC) (Autism Speaks, Research on High Risk Baby Sibs: http://www.