While research progress pertaining to autism spectrum disorder (ASD) has been extraordinary in some areas, many critical gaps in knowledge remain, particularly with respect to the development of treatments that address primary neurobiological abnormalities in affected individuals. For example, almost all children with fragile X syndrome (FXS), the most common known genetic cause of ASD, exhibit symptoms of severe social anxiety, manifested by high levels of social gaze avoidance and other social escape behaviors during interactions with others. To date, however, behavioral treatments designed to ameliorate these intransigent and socially stigmatizing behaviors have not been evaluated. We propose to address this critical knowledge gap by evaluating a 3-day treatment probe targeted to improving social gaze behavior in children with FXS using the principles of Applied Behavior Analysis (ABA). Importantly, we propose to examine the effects of this treatment probe on brain and behavior. Two groups of subjects will be recruited in the study: 1) Boys with FXS aged 10 to 15 years (N = 40), and 2) age- and symptom-matched children who do not have FXS (N=40). Participants will travel to Stanford for a 5-day evaluation. Participants in each group will be randomized to receive either Social Gaze Training conducted in 2 x 1hr sessions per day on Days 2, 3 and 4 (total training time = 6 hours) or No-Training which will consist of equivalent amounts of therapist time and reinforcement over the same time period, but with no training of social gaze behavior. We will measure change in social and neurobiological functioning by conducting standardized behavioral and neuroimaging assessments on Day 1 and Day 5. For the behavioral assessment, appropriate social behavior will be measured during a standardized social challenge assessment conducted with an eye-tracker. For the neurobiological assessment, salience network activation will be measured using resting-state fMRI. To assess the longer-term effects of social gaze training in terms of durabilit and generalizability, we have included a 4-week follow-up assessment in which standardized questionnaires of everyday social functioning will be administered. The results of this study promises to provide important information regarding both behavioral effects and brain-behavior associations following skills training in FXS that will form the foundation of future studies of social processing in FXS and ASD. This study will therefore have a significant impact on intervention designs and treatments for children with FXS and other disorders associated with ASD symptomatology, both now and in the future.

Public Health Relevance

The proposed study will be the first of its kind to examine the effects of teaching specific social skills, using the principles of Applied Behavior Analysis (ABA) on core symptoms of social anxiety in individuals with fragile X syndrome (FXS), the most common known form of inherited intellectual disability and genetic cause of ASD. The results of this study therefore promises to provide important information regarding both behavioral effects and brain-behavior associations following skills training in FXS that will form the foundation of future studies of social processing and treatments in FXS and ASD.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD081336-04
Application #
9417039
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
King, Tracy
Project Start
2015-04-01
Project End
2020-01-31
Budget Start
2018-02-01
Budget End
2019-01-31
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Stanford University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94304
Hall, Scott S; Venema, Kaitlin M (2017) A Screening Tool to Measure Eye Contact Avoidance in Boys with Fragile X Syndrome. J Autism Dev Disord 47:2254-2264