Executive functioning and local-global visual processing: Candidate endophenotypes for autism spectrum disorder?

Background: Heterogeneity within autism spectrum disorder (ASD) hampers insight in the etiology and has stimulated the search for endophenotypes. Endophenotypes should meet several criteria, the most important being the association with ASD and the higher occurrence rate in unaffected ASD relatives than in the general population. We evaluated these criteria for executive functioning (EF) and local-global (L-G) visual processing. Methods: By administering an extensive cognitive battery that increases validity of the measures, we examined which of the cognitive anomalies shown by ASD probands also occur in their unaffected relatives (n = 113) compared to typically developing (TD) controls (n = 100). We also provided an overview of studies investigating EF and L-G processing in ASD relatives. Results: For EF, ASD relatives - like ASD probands - showed impairments in response inhibition, cognitive flexibility and generativity (particularly ideational fluency), and EF impairments in daily life. For L-G visual processing, the ASD relatives showed no anomalies on the tasks, but they reported more attention to detail in daily life. Group differences were similar for siblings and for parents of ASD probands, and yielded larger effect sizes in a multiplex subsample. The group effect sizes for the comparison between ASD probands and TD individuals were generally larger than those of the ASD relatives compared to TD individuals. Conclusions: Impaired cognitive flexibility, generativity (specifically ideational fluency) and response inhibition are strong candidate endophenotypes for ASD. Despite resistance to endophenotypic approaches in psychiatry, we argue that endophenotypes are important to bridge the gap between genes and behavior.status: publishe