Jane E. Roberts - US grants

? DESCRIPTION (provided by applicant): Autism spectrum disorder (ASD) is a devastating and common neurodevelopmental disorder and a major public health concern. Fragile X syndrome is the leading known genetic cause of autism, and both fragile X syndrome and the FMR1 premutation are highly associated with autism with ~70% and ~20% meeting DSM- criteria respectively. This proposal extends our initial study, Emergence and Stability of Autism in Fragile X, focused on behavioral symptoms and biomarkers of ASD risk in infants with fragile X syndrome and fragile X premutation at 6,9,12 and 24 months contrasted to siblings of children with idiopathic ASD and typical controls. This proposal represents longitudinal surveillance at 3, 4 and 5 years-of-age in our cohort of 158 infant participants. Our initial findings have fueled a new set of questions to enhance our knowledge of the emergence of ASD features, diagnoses and associated features in FXS and FXpm, including the prevalence and stability of ASD diagnoses FXpm, the stability of ASD core features focused across a continuum, the association of atypical attention and social fear as additive or independent associated features and the predictive value of infant-derived prodromal features to ASD diagnoses across preschool.

DESCRIPTION (provided by applicant): Autism is a devastating and common developmental disorder and a major public health concern. Early detection of autism in high risk infants is critical to these children, their families, and the systems that support them. Fragile X syndrome (FXS) is the leading genetic cause of autism, and both FXS and the FMR1 premutation (FXpm) are highly associated with autism. Despite the high association of autism and FMR1 gene mutations, no study has examined early indicators of autism in FXS or FXpm or examined specificity of early autism indicators in FX to idiopathic (non-FX) autism. This application Emergence and Stability of Autism in Fragile X Syndrome proposes a longitudinal prospective study of the early autism features in infants with FXS and FXpm at 9, 12, and 24 in contrast to infants with an older sibling diagnosed with autism (hereafter referred to as ASIBS) and typical controls (TD). This application takes advantage of recent scientific advances in the identification of autism in the first 2 years of life, characterization of the FXS and FXpm-autism co-morbidity and findings from developmental neuroscience to identify underlying physiological mechanisms associated with early emerging autistic features (e.g., attention). This work will advance our understanding of the progression of autism features during the key risk transition period for two conditions of major health importance: FX and autism. In this project, we will use a combined behavioral, both standardized and laboratory measures, and biomarker approach focused on autistic behavior as a continuum rather than rigid diagnostic categories.

ABSTRACT Given the high prevalence and substantial impact of mental illness on individuals with intellectual disabilities (ID) studies that examine mental health in persons with ID are critical to direct treatment aimed at reduction and, more importantly, prevention of mental illness to improve functioning and quality of life. Fragile X syndrome (FXS) is the leading identified cause of ID with up to 80% of adolescents and adults with FXS meeting criteria for an anxiety disorder. FXS is an ideal model to investigate the combined and interactive effects among biological, behavioral and environmental factors on the emerging trajectory of anxiety in persons with ID. This application ?Emergence, Stability and Predictors of Anxiety in Fragile X Syndrome? proposes the first longitudinal prospective developmental study of the early features of anxiety in very young boys with FXS contrasted to boys diagnosed with ASD (non-FXS) and typical controls (TD). We are interested in the age at which initial features of anxiety can be detected and the stability and prognostic value of these early symptoms to diagnostic categorization across two populations associated with ID and at high risk for anxiety. Likewise, we are interested in documenting factors that predict the emergence, stability and severity of anxiety in these two populations.