Eye Movement Abnormalities in Individuals with ASD and Their Unaffected Biological Parents

Background:   Eye movement studies provide a precisely quantifiable and translational method for studying sensorimotor impairments in autism spectrum disorder (ASD), and could provide insights into its pathophysiological mechanisms. Individuals with ASD show reduced accuracy of both rapid, saccadic eye movements and sustained smooth pursuit eye movements. Additionally, we have identified reduced accuracy of saccades and smooth pursuit eye movements in unaffected first-degree relatives of individuals with ASD. Oculomotor abnormalities thus represent promising intermediate phenotypes, or biological alterations intermediate between genes and overt clinical manifestations that are expressed in both affected individuals and their unaffected first-degree biological relatives. The extent to which oculomotor abnormalities in ASD are familial has yet to be determined. 

Objectives:   To examine saccadic and smooth pursuit eye movements in individuals with ASD and their unaffected parents, and determine the extent to which eye movement deficits co-segregate within families. 

Methods:  Forty-five family trios (proband with ASD, biological mother, biological father) and 81 age-, IQ- and gender-matched controls (39 proband controls, 42 parent controls) completed eye movement testing. Participants with ASD were between ages 5-22 years and had a Performance IQ > 70. Individuals >55 years of age were excluded to limit variable age-related effects on motor functioning. All participants completed 60 trials of a visually-guided saccade task during which they made saccades to peripheral targets that appeared unpredictably but with equal probability at 12 or 24 deg to the left or right of center. The accuracy and latency of each saccade were examined. Participants also completed 40 trials of a smooth pursuit eye movement task during which they tracked targets moving leftward or rightward from center at 4, 8, 16, 24, or 32 deg per second. To determine smooth pursuit accuracy, we computed the velocity of pursuit eye movements relative to the target velocity. 

Results:   Individuals with ASD showed reduced accuracy of both saccadic and smooth pursuit eye movements. We will report results for the following ongoing analyses of our family data: 1) comparisons of saccade and smooth pursuit accuracy between our 90 unaffected biological parents of individuals with ASD and 50 matched parent controls; and 2) the interrelationship between oculomotor accuracy across probands and their unaffected parents. We also will test the association between eye movement abnormalities and broader autism phenotypic characteristics in parents as measured by the Broader Autism Phenotype Questionnaire (BAP-Q).

Conclusions:   Our results indicate that saccadic and smooth pursuit eye movements are reduced in accuracy in ASD. We have previously shown that these deficits may be present in unaffected first-degree relatives, but the familiality of these deficits has not been directly assessed. In this study, we will report the extent to which saccadic and smooth pursuit eye movement abnormalities are present in unaffected biological mothers and fathers of individuals with ASD, and whether these deficits co-segregate in different families. To the extent that these deficits are present in families, our results may help establish oculomotor deficits as biological intermediate phenotypes associated with ASD useful for identifying pathophysiological mechanisms and resolving heterogeneity in this disorder.