Intranasal oxytocin enhances visual fixation to the face in individuals with Autism Spectrum Disorder: a dose-response study 公开

Abstract

There are currently no pharmacological treatments targeting the core social deficits in Autism Spectrum Disorder (ASD). Previous studies have examined the effects of intranasal oxytocin (IN-OXT), a neuropeptide known to be a key modulator in social cognition, as a possible treatment. While acute administration of IN-OXT showed promising results on several primary outcomes related to social cognition, chronic intake led to inconclusive results in terms of efficacy of treatment. Research calls for a dose-dependent study to determine the specific actions of IN-OXT on brain and behavior to optimize its use as hormonal treatment for future studies in patients with ASD. In this present randomized, double-blind, placebo-controlled, dose-response, within-subject study, we examined the effects of different doses of IN-OXT (8 IU, 24 IU, 48 IU) and placebo on eye gaze in adults with high-functioning ASD (18- 45 years old), and compared it to healthy controls’ baseline (with placebo intake) during an fMRI study. Outcome measures included visual fixation time on different areas of interest (AOI) (face, eyes, mouth, forehead, outside face) while observing video stimuli of morphed emotional faces during a Face Perception Task (FPT). We found that IN-OXT enhances visual fixation time to the face in a dose-dependent way, with higher doses of IN-OXT leading to more time looking at faces. In addition, visual fixation time to the face (but not to the other AOIs) was significantly different between healthy controls and ASD individuals who received placebo and low dose (8IU) of IN-OXT. Middle (24 IU) and high (48 IU) doses of IN-OXT were able to normalize their visual fixation to the face similar to healthy controls. This study shows promising results of IN-OXT in enhancing saliency to social stimuli and, possibly, the motivation to attend to faces. It also emphasizes the need for future studies investigating individual differences and the best treatment approaches to alleviate the social deficits in ASD.

Table of Contents

Table of Contents

Abstract……………………………………………………………………………………………………………………………………..1

Background………………………………………………………………………………………………………………………………..3

Eye Tracking and ASD……………………………………………………………………………………………………..4

Treatments and ASD – Oxytocin……………………………………………………………………………………..5

           Figure 1. The OXT System………………………………………………………………….…………………7

Intranasal Oxytocin and Social Cognition………………………………………………………….……………..7

           Intranasal Oxytocin and ASD…………………………………………………………………………………………..8

           Aims and Hypotheses………………………………………………………………………………………….………..10

Methods………………………………………………………………………………………………………………………………….11

           Participants………………………………………………………………………………………………………………….11

Table 1. Demographics and general characteristics of ASD participants randomized to receive IN-OXT ………12

Study Design and Setting………………………………………………………………………………………………13

Procedure…………………………………………………………………………………………………………………….13

Drug Protocol……………………………………………………………………………………………………………….13

Face Perception Task……………………………………………………………………………………………….……14

           Figure 2. Face Perception Task (FPT)………………….………………………………………………15

Eye tracking technology……………………………………………………………………………………….……….16

Data Analysis……………………………………………………………………………………………………..…………16

Figure 3. Representation of determined AOI regions for a female face stimuli.. …………………………17

                      Table 2. Summary of data excluded from analysis…………………………………….………18

Results…………………………………………………………………………………………………………………………19

           Tests of Main Hypotheses………………………………………………………………………………..……………19

           Aim 1………………………………………………………………………………………….…………………………………19

Figure 4. Effects of different doses of IN-OXT on visual fixation time in ASD..........20

Figure 5. Heat map demonstrating eye gaze recording during different doses of IN-OXT and placebo in ASD participants.….21

           Aim 2………………………………………………………………….…………………………………………………………22

Figure 6. Visual fixation time to the face comparing healthy controls to ASD patients after placebo and low dose of IN-OXT……………22

Figure 7. Heat map comparing baseline activity of controls and ASD individuals administered placebo and low dose of IN-OXT……….23

           Aim 3…………………………………………………………………………………............................................................................................24

Figure 8. Visual fixation time to the face comparing healthy controls with ASD patients after middle and high dose of IN-OXT administration……… 24

Figure 9. Heat maps demonstrating baseline activity of controls administered placebo and ASD individuals administered middle dose and high dose of IN-OXT………………………………25

Discussion………………………………………………………………………………………………………………………..………26

           Results and Implications…………………………………………………………………………….…………………26

           Implications and Future Directions……………………………………………………………………………….29

           Conclusions…………………………………………………………………………………………………………..……..31

References………………………………………………………………………………………………………………………..…..…32

Supplementary Figures………………………………………………………………………..…………….…………….…..….43

Supplemental Table 1. Results of earlier clinical trials investigating the effects of IN-OXT on ASD participants……………43

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Neuroscience Psychology, Behavioral Sciences Psychology, Clinical
关键词	autism, oxytocin, visual fixation, eye gaze, social cognition, face perception
Committee Chair / Thesis Advisor	Larry J. Young, Emory University Elissar Andari, Emory University
Committee Members	James K. Rilling, Emory University Jessica Barber, Emory University

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