An Investigation of Neuropsychological Endophenotypes in Autism and Fragile X

DESCRIPTION (provided by applicant): This study is an investigation of neuropsychological functioning of Fragile X carriers with the aim of identifying endophenotypes (i.e., sub-clinical markers of disease present among both affected and unaffected individuals) common to autism and Fragile X. Endophenotypes are thought to reflect more elementary phenomena (or the more basic components of a complex phenotype) and, thus, to be more closely related to underlying pathophysiology than downstream clinical outcomes that are often thought of as a synthesis of a number of such endophenotypes. Endophenotype-based approaches may therefore offer a useful approach for elucidating gene-brain-behavior relationships in neurogenetic disorders such as autism and Fragile X. Evidence of an autism endophenotype was first reported in the landmark twin study of Folstein and Rutter (1977), which described characteristics more subtly expressed, but qualitatively similar to the core features of autism (commonly referred to as a Broad Autism Phenotype) among unaffected twins. In our current NC STAART Autism Research Center, we have examined the neuropsychological basis of the Broad Autism Phenotype, and have identified abnormalities in social cognition among parents of individuals with autism, on tasks linked in previous studies to specific brain regions in the neural circuitry of social cognition. This application proposes to administer this same battery of tasks to mothers of individuals with Fragile X (premutation carriers) to investigate possible deficits which could suggest common etiological pathways underlying autism and Fragile X. Neuropsychological profiles within the Fragile X parent group will be compared with data previously collected from parents of autistic individuals and controls. Although clinical features thought to be related to premutation FMR1 status have been reported among FRX carriers, to date, no study has examined such features in relation to the Broad Autism Phenotype. By comparing the behavioral and neuropsychological characteristics of individuals with genetic liability to Fragile X and autism, this study aims to provide new insights into the forme fruste of the autism and Fragile X neuropsychological phenotypes for use in future genetics, brain, and behavioral studies of these disorders. PUBLIC HEALTH RELEVANCE: This application proposes to investigate the overlap of autism and FXS by studying heritable, sub-threshold features among parents of autistic individuals and parents of individuals with FXS. By characterizing the behavioral and neuropsychological functioning of parents, we aim to pinpoint traits of greatest genetic significance, and importantly, determine whether such characteristics show overlap among individuals with genetic susceptibility to these disorders.