Title: Cognitive endophenotypes of autism spectrum disorders: Executive functioning and local-global visual processing
Authors: Van Eylen, Lien
Issue Date: 17-Dec-2014
Abstract: Autism Spectrum Disorders (ASD) are early onset neurodevelopmental disorders characterized by the co-occurrence of impairments in social reciprocity and communication, accompanied by a rigid and repetitive pattern of interests and activities. The disorder has a high heritability, but insight in the aetiology is still limited, mainly due to considerable heterogeneity between individuals with ASD. This large heterogeneity stimulates the search for 'endophenotypes' that allow us to delineate more homogeneous subgroups. Endophenotypes are phenotypes that are more proximal to the biological aetiology of a clinical disorder than its signs and symptoms, and are influenced by one or more of the same genes that confer susceptibility to the condition. In other words, they are intermediate phenotypes that mediate the relationship between genotype and behavioural traits of the disorder. Additionally, endophenotypes are supposed to be ‘biomarkersÂ’ that are less genetically complex than the disorder they underlie. Therefore, endophenotypes may be particularly useful for understanding the aetiology of complex disorders, such as ASD and to unravel biological pathways from genes to behavioural characteristics of the disorder.Neurocognitive characteristics are potentially interesting ASD endophenotypes, since they provide a crucial interface between brain and behaviour. This project focusses on two dominant neurocognitive accounts for ASD: 1) the Executive Functioning (EF) theory and 2) the Weak Central Coherence account of alterations in local-global processing in individuals with ASD. The general aim of this dissertation is to assess which aspects of EF and local-global visual processing provide good endophenotype candidates for ASD. In view of the problematic validity of existing EF and local-global processing measures, we first developed a neurocognitive battery aimed to increase the validity of these measures. In this battery a distinction was made between five EF domains (inhibition, cognitive flexibility, generativity, working memory and planning), and between local versus global visual processing abilities and visual processing style. Good ASD endophenotypes have to meet several criteria, of which two are addressed here, namely: they should co-occur with ASD and they are expressed at a higher rate in unaffected first degree relatives of probands with ASD than in the general population. To evaluate these criteria, the neurocognitive battery was administered to children and adolescents with ASD, their first degree relatives and Typically Developing (TD) controls (N = 306). When comparing individuals with ASD and TD individuals, we found that individuals with ASD showed impairments in all EF domains, but deficits were more pronounced in (and sometimes even restricted to) open-ended compared to highly structured settings. Furthermore, they displayed a more locally oriented processing style, intact local processing abilities and selective global processing impairments on tasks with high integrative demands. The first degree relatives of these probands with ASD shared EF difficulties in response inhibition, cognitive flexibility and generativity measured with EF tasks, and they showed EF impairments in daily life. For local-global visual processing, ASD relatives did show more attention to detail in daily life compared to TD individuals, but no group differences were found on any of the more controlled tasks. These findings suggest that mainly impairments in response inhibition, cognitive flexibility and generativity are valuable endophenotype candidates for ASD. However, further research is needed to replicate these findings and to evaluate the additional endophenotype criteria. Finally, we address some remaining issues regarding phenotypic and cognitive heterogeneity and provide suggestions for clinical practice.<i style="mso-bidi-font-style:normal"><span style="font-size:11.0pt;font-family:&quot;Calibri&quot;,&quot;sans-serif&quot;;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:Calibri;mso-bidi-theme-font:minor-latin;mso-ansi-language:EN-GB" lang="EN-GB"><span style="font-size:11.0pt;font-family:&quot;Calibri&quot;,&quot;sans-serif&quot;;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:Calibri;mso-bidi-theme-font:minor-latin;mso-ansi-language:EN-GB;mso-fareast-language:EN-US;mso-bidi-language:AR-SA" lang="EN-GB">
Publication status: published
KU Leuven publication type: TH
Appears in Collections:Parenting and Special Education
Laboratory for Experimental Psychology
Research Group Psychiatry

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