The Emergence of Autism and Atypical Social Functioning in Children with Neurofibromatosis Type 1: From Toddlerhood to Early Adolescence
Abstract
Rationale and Objective: Social dysfunction is common in neurofibromatosis type 1 (NF1). Impaired social skills result in poor peer relationships and can have negative implications for mental health, career achievement, and quality of life. We currently know very little about what is causing social dysfunction in NF1. It is also unclear why 25% of school-aged children with NF1 meet the diagnostic criteria for autism spectrum disorder (ASD), a behavioral condition associated with significant impairments in social interaction, communication, and behavior. The ultimate goal of our research is to create a knowledge platform to enable optimal design of future intervention studies. For these studies to have the most meaningful clinical impact, we need to (1) fully understand the problem and how it impacts the day-to-day functioning of children with NF1 and (2) understand the underlying causes of these behavioral deficits. These objectives, which form our study aims, will enable future intervention studies to use appropriate and clinically relevant treatment targets, appropriate outcome measures for measuring behavioral change, and will also guide the design of therapeutic interventions. More specifically, this study will be the first to use gold standard diagnostic, cognitive, and behavioral assessments to investigate the frequency of ASD in young (3-5 years) and school-aged children (6-12 years) with NF1. Our study design enables us to understand the psychological processes contributing to ASD symptom severity and poor social behavior in these children. Our study will be the first to determine the frequency of ASD in a large cohort of young children with NF1 (toddlers and pre-schoolers). This is particularly important to establish, given early detection of ASD is essential to enable early intervention. In addition to children with NF1, we will also include a matched group of children with ASD from the general population (i.e., without NF1) to help us understand whether ASD in NF1 is the same as autism in the general population. This will be the first study to systematically evaluate how ASD in the context of NF1 may differ from that in the general population and will help validate the diagnosis in NF1. A particularly innovative aspect of our study is the use advanced neuroimaging techniques to understand brain abnormalities contributing to ASD and social impairment in children with NF1. Specifically, using noninvasive methods, we will test the hypothesis that abnormal brain connections and brain function underlie the observed behavioral impairments. Ultimate Applicability and Contributions of Research: This study addresses a critical need in the NF1 community and will result in significant advances in NF1 research and patient care. It will guide the development of future treatments for children with NF1 who are experiencing social issues and/or increased levels of ASD symptoms by identifying how early ASD can be detected, and thus treated. Given strong evidence that early intervention (3-5 years) in children with ASD (without NF1) results in dramatically improved outcomes and considerable cost savings to families and health systems, early identification is critical to altering the trajectory of social and behavioral dysfunction in NF1. Establishing an increased prevalence of ASD in young children with NF1 will also help shape current NF1 patient guidelines, such as introducing routine screening procedures for young children with NF1 into clinic practice. Importantly, by studying ASD in NF1 (a well-defined medical condition with known biochemical abnormalities) and comparing it to ASD in the general population, we gain more knowledge about ASD in the general population. Within this context, NF1 may provide a human model of ASD, similar to the way animal models provide simple systems to study complex disorders. This research will also enable the identification of treatment targets for future interventions
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510619
Entities
People
- Kathryn North
Organizations
- United States Army