New Evidence of An Endophenotype Associated with Impaired Shifting Attention In Male Siblings of Probands with Autism

Background:  

Studies have shown deficits in rapidly shifting attention between auditory and visual modalities in individuals with known cerebellar pathology and who have a neurodevelopmental disorder associated with abnormal cerebellar growth, such as autism or Williams syndrome.  Research also provides evidence for a broader phenotype of autism, characterized by autistic-like traits observed in biological relatives of autistic individuals.

Based on the strong influence that genetics play in the presence of autism and the broad phenotype often seen in first-degree relatives of individuals with autism, it is possible that typically developing siblings of children with autism might have subtle abnormalities affecting subcortical and cortical structures including the cerebellum or cerebellar-frontal systems.  This could be indexed by difficulty in their ability to rapidly shift attention.       

Objectives:  

This study examined shifting attention abilities in typically developing male siblings of children with autism in order to identify whether shifting attention deficits may be an aspect of the broader autism phenotype.

Methods:

Participants included 20 typically developing males with a first-degree sibling with a diagnosis of autism (SIB) and 19 typically developing males with a typically developing first-degree sibling (NC), ages 8-16 years. 

Participants were asked to participate in computerized attentional tasks.  Each task required the participant to selectively attend to the designated stimulus modality, discriminate between targets, and exhibit a simple motor response (button press) to the detected targets. 

The focus attention tasks required the participants to attend and respond to targets in the designated stimulus modality while ignoring targets in the other modality.   Targets consisted of a red or green square (visual modality) or a high or low tone (auditory modality).  The shifting attention tasks required the participants to detect a target in one stimulus modality, which served to then signal the disengagement of attention from the current modality and to shift to attend to the other modality.

The participant’s responses were then categorized into five time bins (0.4 seconds to greater than 30 seconds).  The time bins indicate the length of time between the presentation of the cue and the target stimuli.  Responses from each time bin were then noted as hits, misses, false alarms, response accuracy (hits/hit+misses), and reaction time (in milliseconds). 

Results:

The SIB and NC groups were significantly different in the first time bin (auditory: p=0.043; visual: p=0.002). The difference between the SIB and NC groups was not statistically significant in any of the focus condition time bines.

Conclusions:   

When required to do so with less than 2.5 seconds, male siblings showed statistically significant lower response accuracy on both the auditory and visual shifting attention tasks as compared to matched controls. Male siblings demonstrated a pattern of functioning similar to that reported of persons with autism or known cerebellar abnormality.             

This study provides support for an autism endophenotype involving rapid intermodality deficits in shifting attention and calls for future research examining gender differences in the expression of such a phenotype.  Further research on how genetics influences the cerebellum and cerebellar-frontal system in autism and other neurodevelopmental disorders is warranted.