Visual Fixation Preferences in Autism: A Randomized Controlled Trial of Intranasal Oxytocin

Background:   Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by severe social/communication deficits, repetitive behaviors and fixated interests (proposed DSM-5 criteria). Recently, studies have shown that the neuropeptide oxytocin enhances social communication while reducing repetitive behaviors in some ASD patients (Andari et al. 2010; Guastella et al. 2010; Hollander et al. 2003). However, no prior study has examined the effect of oxytocin on fixated interestes in children with ASD.

Objectives:  The objective of this study was to examine the effect of intranasal oxytocin on fixated interests in children and adolescents with ASD.  We hypothesized that ASD subjects would show a visual preference for more highly organized or structured (“systemized”) real-life photographs, compared with matched control subjects, and that this preference would be reversed after administration of intranasal oxytocin. 

Methods:   As part of a randomized double blind placebo-controlled crossover study, 32 subjects (16 ASD and 16 matched control males; mean age 13 years; range 8-19 years) were administered either intranasal oxytocin or placebo on their first study visit and the alternate solution on a subsequent visit two weeks later.  Oxytocin administration was counterbalanced between subjects across study visits. On each occasion, participants then viewed 14 slides, each containing four related pictures that differed on the degree of systemization (i.e. different arrangements of people, animals, objects or scenes). Picture position on each slide was pseudo-randomized across study participants. Visual preference was determined using an automated eye tracker which calculated fixation times and counts within each of the four regions of interest. Mixed-effects linear regression models were used to determine the relationship between oxytocin administration and visual fixation preferences in ASD and control subjects, adjusting for visit order and picture position.

Results:   Significant 3-way interactions were found for both fixation time and count; oxytocin significantly reduced the tendency for ASD subjects to view more highly systemized pictures compared to receiving placebo, whereas the opposite pattern was seen for control subjects. Oxytocin significantly reversed the preference of ASD subjects to view more highly systemized pictures.

Conclusions: This study provides additional evidence for the potential benefits of oxytocin in ASD to diminish fixated interests, in addition to reducing repetitive behaviors and enhancing social communication.