Adolescents diagnosed with fragile X syndrome (FXS), the leading known cause of inherited intellectual disability, commonly engage in severe disruptive behaviors (i.e., self-injury and aggression) that can significantly impact the individua's educational progress and functioning. However, the biological and behavioral mechanisms underlying these pathological behaviors are very poorly understood. In this proposal, we aim to examine the extent to which autonomic nervous system arousal interacts with environmental factors (positive and negative reinforcement processes) to exacerbate and maintain self-injury/aggression in FXS. Screening of potential participants will be conducted using the Functional Analysis Screening Tool(c) which will allow us establish the prevalence, frequency, severity, and circumstances surrounding the occurrence of self- injury/aggression in FXS. We will also screen individuals with intellectual disability (ID) who do not have FXS. From the screening, 30 individuals with FXS and 30 ID controls will be selected to travel to Stanford University for a 3-day assessment of their self-injury/aggression. These participants will be aged 11 to 18 years and engage in self-injury/aggression with moderate to severe intensity on a daily basis. Participants with FXS will be matched to ID control participants with respect to age, functioning level, and degree of autistic symptom severity. This comparison group will allow us to determine whether the behavioral characteristics of FXS are specific to FXS, or characteristic of individuals with ID in general. Each subject will undergo a Functional Analysis, conducted by a Board Certified Behavior Analyst, to identify the environmental factors maintaining the child's self-injury/aggression. The Functional Analysis will include both standard and """"""""FXS-specific"""""""" conditions (e.g. transitions and social demands). To examine the influence of physiological factors, we will measure physiological responses and salivary cortisol levels both at Baseline and during the Functional Analysis. The results of this project will directly help individuals with FXS and their families, as well as greatly advance the understanding of self-injury/aggression in FXS, providing sorely needed empirical data to inform interventions in the future for both FXS and other individuals with ID. The project will also significantly improve our understanding of the complex interplay between physiological and environmental factors in co-morbid behaviors in individuals with FXS.

Public Health Relevance

Adolescents with Fragile X syndrome (FXS) commonly show severe disruptive behaviors (i.e., self-injury, aggression) that can seriously impact the individual's quality of life, education, and overall functioning. Furthermore, these behaviors cause significant distress to families and caregivers. However, there have been no systematic investigations aimed at understanding the complex interplay between physiological and environmental factors contributing to these common FXS-associated co-morbid behaviors. Our proposed study will be the first to target these important problematic behaviors using standardized and innovative assessment methodologies.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Exploratory/Developmental Grants (R21)
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Child Psychopathology and Developmental Disabilities Study Section (CPDD)
Program Officer
Urv, Tiina K
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Stanford University
Schools of Arts and Sciences
United States
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Hall, S S; Hustyi, K M; Barnett, R P (2018) Examining the influence of social-environmental variables on self-injurious behaviour in adolescent boys with fragile X syndrome. J Intellect Disabil Res 62:1072-1085
Hall, S S; Barnett, R P; Hustyi, K M (2016) Problem behaviour in adolescent boys with fragile X syndrome: relative prevalence, frequency and severity. J Intellect Disabil Res 60:1189-1199