Development of Behavioral and Neural Biomarkers for Autism Spectrum Disorder Using a Genetically Defined Subtype



 DESCRIPTION (provided by applicant): Autism spectrum disorder (ASD) affects 1 in 68 children (CDC, 2014) with known genetic causes accounting for 10-15% of cases (Devlin & Scherer, 2012; Gaugler et al., 2014). Approximately 2% of severely affected children with ASD have deletions or point mutations in the SHANK3 gene, which results in Phelan- McDermid syndrome (PMS) (Betancur & Buxbaum, 2013; Leblond et al, 2014). SHANK3 is a scaffolding protein in glutamate synapses (Bodzdagi et al., 2013; Yang et al., 2012). Over 80% of children with PMS meet Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for ASD and intellectual disability and are minimally verbal (Soorya et al., 2013). Sensory reactivity abnormalities such as hypo- and hyper-reactivity represent a new DSM-5 criterion for ASD. While sensory reactivity issues have been shown in idiopathic forms of ASD (Tomcheck & Dunn, 1997; Tavassoli et al., 2012, 2013), no studies have investigated sensory reactivity abnormalities in severely affected children, including those with PMS. Identifying sensory reactivity abnormalities is especially important in such children as they cannot verbally describe their sensory experiences. In idiopathic forms of ASD, vision is the most researched sensory modality (Simmons et al., 2009; Tavassoli et al., 2011; Weinger et al., 2014). Moreover our pilot studies suggest that hyporeactivity in the visual domain is common in children with PMS. Preliminary data also show that behavioral and electrophysiological measures of sensory reactivity may have the capacity to objectively differentiate between children with (1) PMS, (2) idiopathic ASD, and (3) typically developing controls. The aim of the proposed project is to develop behavioral and neural biomarkers of sensory reactivity in ASD, which are feasible in severely affected individuals (including PMS) and can be translated to other genetically defined subtypes and across sensory modalities. This project aims to develop reliable measures of behavioral and neural sensory reactivity within the visual system of children with PMS and ASD more broadly. The knowledge gained will provide an enhanced understanding of how one sensory system is affected in PMS and ASD, while assessing the relationship with neural functioning. This study is important because it seeks to develop biomarkers that can be applied to other clinical populations of severely affected individuals.