The Endophenotype of Executive Function: A Pilot Study in Twins

Background: Autism Spectrum Disorder is a heterogeneous disorder, marked by impairments across multiple domains, including social processing, communication, and executive function (EF). Given the varied distribution of impairment and functioning, it may be that ASD is comprised of distinct endophenotypes, which may be inherited separately and exist in individuals even in the absence of the full disorder.  One way to measure this hypothesis is to look at these traits in monozygotic (MZ) and dizygotic twins (DZ). 

Objectives: This pilot study will examine the potential for measuring EF as an endophenotype of autism, and help to determine the types of measures that may be most sensitive to the elements of EF that are shared within MZ and DZ twin pairs.  We will examine performance on a battery of EF tasks and determine which show high levels of performance similarity within twin pairs.  To ensure that the measure is also sensitive to the EF impairments present in autism, we will also compare the performance of ASD individuals to that of typically developing individuals.  

Methods: Preliminary data was available for ten pairs of twins (8 MZ, 2 DZ) ages 8 to 21.  Individuals tested included both typically developing individuals (N = 13) and those with autism (N = 7).  Behavioral tasks included three Delis-Kaplan executive function (D-KEFs) battery subtests: Trail Making, Verbal Fluency, and Design Fluency (Delis et al., 2001).  The parent and teacher Behavior Rating Inventory of Executive Function (BRIEF) were collected (Gioia et al, 2000).

Results: Scores on the verbal fluency tasks were correlated within twin pairs for overall letter fluency, r (7)= .7, p = .05.  Performance on this task was significantly higher in typically developing individuals (M = 12.2, SD = 3.0) compared to individuals with ASD (M = 9.2, SD = 2.6), t(17) = 2.2, p = .04. 

The global executive composite score derived from the BRIEF was significantly correlated within twin pairs for both parent report, r (8)= .9, p < .01, and teacher report, r(8) = .9, p < .01.  In both cases, individuals with autism were rated as having poorer EF skills than those with typical development, p<.001.

Conclusions: In our small sample of preliminary data, the BRIEF questionnaire (parent and teacher) and the DKEFs letter fluency showed strong correlation within twin pairs and sensitivity to ASD impairment. The BRIEF questionnaire provides a broad view of an individual’s executive functioning as a whole.  The letter fluency task of the DKEFs provides more specific information about EF skills as it requires individuals to call on EF skills such as organization, initiation, and systematic retrieval.  Data collection is ongoing.