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Oxytocin's Impact On Core Brain and Behavioral Features of ASD in Children

Saturday, 4 May 2013: 10:45
Meeting Room 1-2 (Kursaal Centre)
I. Gordon1, R. H. Bennett2, C. Cordeaux1, M. V. Lucas3, B. C. Vander Wyk4, J. F. Leckman1, R. Feldman5 and K. A. Pelphrey1, (1)Child Study Center, Yale University, New Haven, CT, (2)Yale Child Study Center, New Haven, CT, (3)Yale University, New Haven, CT, (4)Yale Child Study Center, Yale University, New Haven, CT, (5)Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan, Israel
Background: The effects of the neuropeptide oxytocin (OT) on a wide range of social behaviors in humans, especially increased sociability, empathy, and theory of mind, provide exciting new potential avenues of exploration for Autism Spectrum Disorders (ASD). Discoveries regarding links between variations in the OT receptor gene and ASD prevalence also highlight the need to assess OT’s impact on both brain and behavior in ASD. Considering the core social dysfunction in ASD, it is crucial to reach a deeper understanding of OT’s behavioral impact, as well as the mechanisms underlying OT’s effects using functional magnetic resonance imaging (fMRI) in children and adolescents with ASD.

Objectives:  Employing a developmental perspective, we aimed to identify the impact of OT on brain regions linked to social motivation, social perception, and social cognition. We also aimed to describe the behavioral impact linked with OT administration in scan-related tasks, as well as in naturalistic social interaction settings. We hypothesized that in fMRI tasks that require processing of social information, OT administration will result in increased activity in regions that play a key role in reward circuitry and key nodes of the social brain. We also expected increased connectivity between these brain regions due to OT’s impact. Finally, we expected aspects of social behavior, such as eye gaze pattern and positive affect, during interactions with participants' parents to become more synchronized with the social partners' cues after OT administration.

Methods:  In the largest study to date (N=20), children with ASD (ages 7-18) were administered an age-appropriate dose of OT. In this double-blind, placebo-controlled study of changes in brain activity after a single dose of OT, we utilized two well-validated fMRI paradigms: Reading the Mind in the Eyes (RMET-R) and Biological Motion Detection. Following administration and prior to the fMRI scan, children and their parents also participated in a videotaped positive interaction paradigm (later to be micro-coded for social behaviors).

Results: Results indicated that administration of OT nasal-spray resulted in increased activity in brain regions known to process social information; specifically, the anterior cingulate and prefrontal cortex, the superior temporal sulcus, temporal parietal gyrus, fusiform, and amygdala.  All of these regions have previously been implicated in their involvement in social perception and cognition, mentalizing abilities, and theory of mind. Similar results emerge in several tasks that involve multiple social information processing routes, thus, emphasizing the potential impact of OT beyond a single task. We will also present first-ever reported behavioral outcomes micro-analyzed from videotaped parent-child interactions.

Conclusions: These results provide the essential steps in devising more effective combination treatments for core social deficits in ASD, which may involve grouping validated clinical interventions with OT administration. Such a treatment approach will fundamentally improve our understanding of autism and its treatment.

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