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J Child Psychol Psychiatry. 2017 Mar;58(3):258-269. doi: 10.1111/jcpp.12637. Epub 2016 Nov 2.

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

Author information

Parenting and Special Education Research Unit, KU Leuven, Leuven, Belgium.
Leuven Autism Research (LAuRes), KU Leuven, Leuven, Belgium.
Child and Adolescent Psychiatry, UPC-KU Leuven, Leuven, Belgium.
Center for Human Genetics, University Hospital Leuven, KU Leuven, Leuven, Belgium.
Brain & Cognition, KU Leuven, Leuven, Belgium.



Heterogeneity within autism spectrum disorder (ASD) hampers insight in the etiology and stimulates 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.


By administering an extensive cognitive battery which increases the 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). Microarrays were performed, so we could exclude relatives from probands with a de novo mutation in a known ASD susceptibility copy number variant, thus increasing the probability that genetic risk variants are shared by the ASD relatives. An overview of studies investigating EF and L-G processing in ASD relatives was also provided.


For EF, ASD relatives - like ASD probands - showed impairments in response inhibition, cognitive flexibility and generativity (specifically, 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.


Impaired cognitive flexibility, ideational fluency and response inhibition are strong candidate endophenotypes for ASD. They could help to delineate etiologically more homogeneous subgroups, which is clinically important to allow assigning ASD probands to different, more targeted, interventions.


Autism spectrum disorder; central coherence; executive functioning; intermediate phenotype; relatives

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