Dataset Information

Heterogeneity of executive functions among comorbid neurodevelopmental disorders.

ABSTRACT: Executive functions (EFs) are used to set goals, plan for the future, inhibit maladaptive responses, and change behavior flexibly. Although some studies point to specific EF profiles in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) - prevalent and often highly comorbid neurodevelopmental disorders - others have not differentiated them. The objective of the current study was to identify distinct profiles of EF across typically developing (TD) children and children with ASD and ADHD. We employed a latent profile analysis using indicators of EF (e.g., working memory, inhibition, and flexibility) in a mixed group of 8-13 year-olds including TD children (n?=?128), children with ASD without ADHD (n?=?30), children with ADHD (n?=?93), and children with comorbid ASD and ADHD (n?=?66). Three EF classes emerged: "above average," "average," and "impaired." EF classes did not reproduce diagnostic categories, suggesting that differences in EF abilities are present within the ASD and ADHD groups. Further, greater EF dysfunction predicted more severe socioemotional problems, such as anxiety/depression. These results highlight the heterogeneity of current diagnostic groups and identify an "impaired" EF group, consisting of children with both ASD and ADHD, which could specifically be targeted for EF intervention.

SUBMITTER: Dajani DR

PROVIDER: S-EPMC5101520 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Heterogeneity of executive functions among comorbid neurodevelopmental disorders.

Dajani Dina R DR Llabre Maria M MM Nebel Mary Beth MB Mostofsky Stewart H SH Uddin Lucina Q LQ

Scientific reports 20161109

Executive functions (EFs) are used to set goals, plan for the future, inhibit maladaptive responses, and change behavior flexibly. Although some studies point to specific EF profiles in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) - prevalent and often highly comorbid neurodevelopmental disorders - others have not differentiated them. The objective of the current study was to identify distinct profiles of EF across typically developing (TD) children and chil ...[more]

PMID: 27827406

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Project description:BACKGROUND:Neurodevelopmental disorders (NDDs) such as autism spectrum disorder, intellectual disability, developmental disability, and epilepsy are characterized by abnormal brain development that may affect cognition, learning, behavior, and motor skills. High co-occurrence (comorbidity) of NDDs indicates a shared, underlying biological mechanism. The genetic heterogeneity and overlap observed in NDDs make it difficult to identify the genetic causes of specific clinical symptoms, such as seizures. METHODS:We present a computational method, MAGI-S, to discover modules or groups of highly connected genes that together potentially perform a similar biological function. MAGI-S integrates protein-protein interaction and co-expression networks to form modules centered around the selection of a single "seed" gene, yielding modules consisting of genes that are highly co-expressed with the seed gene. We aim to dissect the epilepsy phenotype from a general NDD phenotype by providing MAGI-S with high confidence NDD seed genes with varying degrees of association with epilepsy, and we assess the enrichment of de novo mutation, NDD-associated genes, and relevant biological function of constructed modules. RESULTS:The newly identified modules account for the increased rate of de novo non-synonymous mutations in autism, intellectual disability, developmental disability, and epilepsy, and enrichment of copy number variations (CNVs) in developmental disability. We also observed that modules seeded with genes strongly associated with epilepsy tend to have a higher association with epilepsy phenotypes than modules seeded at other neurodevelopmental disorder genes. Modules seeded with genes strongly associated with epilepsy (e.g., SCN1A, GABRA1, and KCNB1) are significantly associated with synaptic transmission, long-term potentiation, and calcium signaling pathways. On the other hand, modules found with seed genes that are not associated or weakly associated with epilepsy are mostly involved with RNA regulation and chromatin remodeling. CONCLUSIONS:In summary, our method identifies modules enriched with de novo non-synonymous mutations and can capture specific networks that underlie the epilepsy phenotype and display distinct enrichment in relevant biological processes. MAGI-S is available at https://github.com/jchow32/magi-s .

Project description:BackgroundExecutive functioning deficits are common in children with neurodevelopmental disorders. However, prior research mainly focused on clinical populations employing cross-sectional designs, impeding conclusions on temporal neurodevelopmental pathways. Here, we examined the prospective association of executive functioning with subsequent autism spectrum disorder (ASD) traits and attention-deficit/hyperactivity disorder (ADHD) traits.MethodsThis study included young children from the Generation R Study, a general population birth cohort. The Brief Rating Inventory of Executive Function-Preschool Version was used to assess parent-reported behavioral executive functioning when the children were 4 years old. ASD traits were assessed at age 6 (n = 3938) using the parent-reported Social Responsiveness Scale. The Teacher Report Form was used to assess ADHD traits at age 7 (n = 2749). Children with high scores were screened to determine possible clinical ASD or ADHD diagnoses. We were able to confirm an ASD diagnosis for n = 56 children by retrieving their medical records and established an ADHD diagnosis for n = 194 children using the Diagnostic Interview Schedule for Children-Young Child version (DISC-YC). Data were analyzed using hierarchical linear and logistic regressions.ResultsImpaired executive functioning was associated with more ASD and ADHD traits across informants (for ASD traits and diagnoses: β = 0.33, 95% CI [0.30-0.37]; OR = 2.69, 95% CI [1.92-3.77], respectively; for ADHD traits and diagnoses: β = 0.12, 95% CI [0.07-0.16]; OR = 2.32, 95% CI [1.89-2.85], respectively). Deficits in all subdomains were associated with higher levels of ASD traits, whereas only impaired inhibition, working memory, and planning/organization were associated with more ADHD traits.ConclusionsThe findings of the current study suggest a graded association of executive functioning difficulties along the continuum of ASD and ADHD and that problems in executive functioning may be a precursor of ASD and ADHD traits from an early age onwards.

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Heterogeneity of executive functions among comorbid neurodevelopmental disorders.

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Heterogeneity of executive functions among comorbid neurodevelopmental disorders.

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