The Effects of a Novel Vasopressin V1a Antagonist on Orienting to Biological Motion

Thursday, May 15, 2014
Atrium Ballroom (Marriott Marquis Atlanta)
F. Shic1, M. del Valle Rubido2, E. Hollander3, S. S. Jeste4, J. T. McCracken5, L. Scahill6, O. Khwaja7, L. Squassante8, E. S. Kim1, M. G. Perlmutter1, E. Sharer9, R. J. Jou10, M. C. Lyons11, T. Apelian12, G. Berlin13, C. J. Ferretti14, A. Gavaletz10, R. L. Loomis15, T. Shimizu16, B. P. Taylor17, C. A. Wall1 and D. Umbricht18, (1)Child Study Center, Yale University School of Medicine, New Haven, CT, (2)Roche, Basel, Switzerland, (3)Psychiatry, Albert Einstein College of Medicine, Bronx, NY, (4)Psychiatry and Neurology, UCLA, Los Angeles, CA, (5)Psychiatry and Biobehavioral Sciences, UCLA Semel Institute for Neuroscience & Human Behavior, Los Angeles, CA, (6)Marcus Autism Center, Atlanta, GA, (7)Neurosciences, F.Hoffmann-La Roche AG, Basel, Switzerland, (8)Product Development, Biometrics, F-Hoffmann-La Roche Ltd., Basel, Switzerland, (9)Kennedy Krieger Insitiute, Baltimore, MD, (10)Child Study Center, Yale University, New Haven, CT, (11)Developmental Disabilities Clinic, Yale University, New Haven, CT, (12)Psychiatry and Biobehavioral Sciences, UCLA Semel Institute CAN Clinic, Los Angeles, CA, (13)Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, (14)111 East 210th Street, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY, (15)Yale University Child Study Center, New Haven, CT, (16)Psychiatry, UCLA Center for Autism Research and Treatment, Los Angeles, CA, (17)Dept. Of Psychiatry and Behavioral Sciences, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, (18)F. Hoffmann - La Roche AG, Basel, Switzerland
Background: Eye tracking has become an increasingly prominent tool in the study of ASDs. However, to date, only a few studies have used eye tracking to monitor the effects of potential interventions and no studies have used eye tracking to systematically evaluate the effects of novel pharmacological agents.

Objectives:  To explore the impact of a novel V1a antagonist, RG4914, on the social attention of high-functioning adults with autism through eye-tracking tasks including biological motion preference.

Methods:  High-functioning adults (M=23.4 years, range=18 to 40 years) with autism (n=19) participated in a multi-center (3-site), randomized, double-blind, placebo-controlled, cross-over study of the the effects of RG4914. Each participant was seen on two separate days for dosing. On the first dosing day, participants completed (1) predose assessments including eye tracking; (2) a 2 hour infusion of RG4914 or placebo; and (3) a postinfusion assessment battery including eye tracking. The second dosing day was similar to the first dosing day, with the exception of a crossover for the IV compound (RG4914 or placebo). Administered eye-tracking tasks included biological motion preference (based on work similar to Annaz et al., 2012). In this preference task, outcome variables included %Looking time towards the biological/social stimulus, %Orienting (% of trials where the first attended to stimulus was the more social target), and Latency (response time to attend to either the social or control stimulus).

Results:  Linear mixed model analyses conducted over data aggregated for each eye-tracking task revealed a significant effect of RG4914 vs. placebo on %Orienting in biological motion preference tasks (p<.05, ES=0.8), with participants administered RG4914 directing their first gaze shift more often to biological motion targets. While similar analyses for Latency were not significant (p>.05), the effect size was moderate (ES=-.4) with trends suggesting that participants administered RG4914 orient more quickly as well as more often to biological information. Primary hypotheses on %Looking for biological motion preference were also not significant; however, an exploratory analysis revealed a significant interaction (p=.05) between the day of dosing and changes between pre- and post-infusion performance, with participants administered a placebo on day 1 showing greater decreases in looking at biological motion as compared to participants administered the active compound.

Conclusions: This study provides preliminary evidence of the ability of a novel V1a antagonist, RG4914, to affect behaviorally primitive and evolutionarily preserved attentional responses to biological motion. Furthermore, this study suggests that eye tracking may be useful not only for monitoring the effects of treatments for individuals with ASD, but may also serve as a valuable tool in the development of new interventions, behavioral, pharmacological, or otherwise. Because of the small sample sizes of this study, and the exploratory nature of both the analyses and the designed experiments, these results should be taken as preliminary.