The Effects of a Novel Vasopressin V1a Antagonist in Combination with Others' Gaze Behaviors on Attention to Others' Heads in Adults with ASD

Saturday, May 14, 2016: 3:16 PM
Room 308 (Baltimore Convention Center)
C. Foster1, M. del Valle Rubido2, J. McCracken3, E. Hollander4, L. Scahill5, L. Boak6, O. Khwaja2, F. Bolognani7, P. Fontoura8, D. Umbricht2, S. S. Jeste9, E. S. Kim10, R. J. Jou11, C. A. Wall1 and F. Shic1, (1)Yale Child Study Center, Yale University School of Medicine, New Haven, CT, (2)F. Hoffmann - La Roche AG, Basel, Switzerland, (3)UCLA Semel Institute for Neuroscience & Human Behavior, Los Angeles, CA, (4)Albert Einstein College of Medicine, Mamaroneck 10543, NY, (5)Pediatrics, Marcus Autism Center, Atlanta 30329, GA, (6)F. Hoffmann-La Roche AG, Basel, Switzerland, (7)F. Hoffmann-La Roche, Basel, Switzerland, (8)Roche Pharma Research and Exploratory Development, Basel, Switzerland, (9)Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, (10)The Children's Hospital of Philadelphia, Philadelphia, PA, (11)Yale Child Study Center, Yale School of Medicine, New Haven, CT
Background:  Oxytocin and vasopressin appear to modulate neural circuitry and behavioral responses associated with social cognition (Zink et al., 2010; Heinrichs et al., 2008), providing a potential target for pharmacological intervention. Eye tracking has been used extensively in ASD research for examining social deficits (Boraston et al., 2007), and it has the potential to be developed as a robust and sensitive outcome measure for clinical trials. 

Objectives:  To explore the impact of a novel vasopressin receptor V1a antagonist, RG7713, vs. placebo on looking patterns influenced by the gaze behaviors of others in high-functioning adults with autism.

Methods:  High-functioning adults (N=17; Mage=23.4 years, range=18 to 40 years) with autism participated in a multi-center randomized, double-blind, placebo-controlled, crossover study of the effects of RG7713. Participants completed two visits following identical procedures with the exception of a crossover for the compound administered (RG7713 vs. placebo).  Participants in dosing Order 1 received RG7713 compound during their first visit (Day 1), while those in dosing Order 2 received RG7713 during their second (Day 2). Visits included: (1) pre-infusion assessments and eye-tracking battery, (2) a 2 hour IV infusion of RG7713 or placebo, (3) post-infusion assessments and eye tracking battery. The eye-tracking battery included an activity monitoring task, in which participants viewed 12 20s video clips of 2 actresses interacting and engaging in a shared activity.  The task was parsed into two gaze conditions: (1) the actresses fixated on the shared play activity (activity gaze), (2) the actresses fixated on each other (mutual gaze). Analyses were conducted to examine the effects of RG7713 vs. placebo on the proportion of time spent attending to the actresses’ heads (%Head).

Results:  Linear mixed model analyses revealed a main effect of drug (p<.05, d=.29) and gaze condition (p<.01, d= 0.53) on %Head. Participants exhibited a larger %Head post-RG4914 vs. both pre-infusion (p <.05, d= 0.15) and post-placebo (p<.01, d=0.24), as well as a larger %Head during mutual gaze trials vs. activity gaze trials (p<.01 d=.53). There was no significant main effect of day of RG7713 administration and no significant interaction effects (p>.05). Results are illustrated in Figure 1.

Conclusions:  These findings provide preliminary evidence of the ability of a novel V1a antagonist RG7713 to augment attention to others’ heads in high functioning adults with ASD. When paired with preexisting response patterns to gaze behaviors of others, administration of RG7713 may result in an optimization of attention to others’ heads. Although the administration of RG7713 did not alter the degree to which attention increased from activity to mutual gaze trials, administration of the compound was associated with an overall heightened amount of time spent attending to heads above both pre-infusion and placebo levels, with attention optimized in post-RG7713 mutual gaze trials. Furthermore, this study suggests that eye tracking may be a useful tool for developing and monitoring treatment effects of novel pharmacological interventions in ASD.