This is an application for a 5-year competing continuation of an ongoing longitudinal (R01) study of autistic social impairment in sibling pairs. Given recent findings regarding the genetic and neurobiologic architecture of autism, it has become clear that a more precise characterization of heritable quantitative components of the autism phenome might accelerate the discovery of specific genetic and neurobiologic causes of autism. This study will involve quantitative phenotyping of 5576 subjects (from 1295 clinically ascertained families of children with and without autism spectrum disorders (ASD). It will include: assessment of parents and affected individuals in extended pedigrees;examination of whether patterns of distribution of quantitative autistic traits in families vary as a function of gender, ethnicity, simplex versus multiplex versus "complex" autism, or other phenotypic covariates;longer-term follow-up of existing longitudinal study subjects to better elucidate the developmental course of autistic social impairment over time;and examination among sib-pairs of novel quantitative endophenotypes (motor, somatosensory, and electrophysiologic) that may relate both to severity of autistic social impairment and to core genetic and neurobiologic determinants of autism. In this application, we have attempted to be responsive to the problem that previous family-genetic studies of autism have often under-represented minority and disadvantaged populations, for whom specific liabilities to autism (if present) would be overlooked in existing studies and data sets. In addition to enhanced phenotypic characterization of this large clinically-ascertained sibling sample, 475 of the families will be genotyped (parents and sibling sets) by either of two ongoing national linkage studies of autism (the Autism Genetic Resource Exchange and the Simons Simplex Collection). In addition to implications for the genetics and neurobiology of autism, the findings from the study will enhance methods for measuring subtle effects of treatment, will identify intervals in the lifespan when interventions might have particular influence on social development, and will elucidate the manner in which functional disability incurred by a wide range of non-ASD child psychiatric conditions, including ADHD can be exacerbated when superimposed (as is common) by the co-occurrence of sub clinical autistic traits.
Autism and related disorders affect 1 out of every 150 children in the US and result in profound social impairment throughout life. This study examines how autistic social impairments change over the course of childhood, how they are transmitted across generations, and which normal developmental processes they disrupt. The results of the study will aid in the search for the genes and neural abnormalities that cause autism, will enhance methods for measuring subtle but important effects of intervention, and will identify intervals in the lifespan when interventions might have their greatest impact on social development in affected children.
|Lyall, Kristen; Constantino, John N; Weisskopf, Marc G et al. (2014) Parental social responsiveness and risk of autism spectrum disorder in offspring. JAMA Psychiatry 71:936-42|
|Frazier, Thomas W; Ratliff, Kristin R; Gruber, Chris et al. (2014) Confirmatory factor analytic structure and measurement invariance of quantitative autistic traits measured by the Social Responsiveness Scale-2. Autism 18:31-44|
|De Alwis, Duneesha; Agrawal, Arpana; Reiersen, Angela M et al. (2014) ADHD symptoms, autistic traits, and substance use and misuse in adult Australian twins. J Stud Alcohol Drugs 75:211-21|
|Messinger, Daniel; Young, Gregory S; Ozonoff, Sally et al. (2013) Beyond autism: a baby siblings research consortium study of high-risk children at three years of age. J Am Acad Child Adolesc Psychiatry 52:300-308.e1|
|Kamio, Y; Inada, N; Moriwaki, A et al. (2013) Quantitative autistic traits ascertained in a national survey of 22 529 Japanese schoolchildren. Acta Psychiatr Scand 128:45-53|
|Frazier, Thomas W; Youngstrom, Eric A; Speer, Leslie et al. (2012) Validation of proposed DSM-5 criteria for autism spectrum disorder. J Am Acad Child Adolesc Psychiatry 51:28-40.e3|
|Constantino, John N (2011) The quantitative nature of autistic social impairment. Pediatr Res 69:55R-62R|
|Jonson-Reid, Melissa; Presnall, Ned; Drake, Brett et al. (2010) Effects of child maltreatment and inherited liability on antisocial development: an official records study. J Am Acad Child Adolesc Psychiatry 49:321-32; quiz 431|
|Constantino, John N; Zhang, Yi; Frazier, Thomas et al. (2010) Sibling recurrence and the genetic epidemiology of autism. Am J Psychiatry 167:1349-56|
|Constantino, John N; Majmudar, Palak; Bottini, Alex et al. (2010) Infant head growth in male siblings of children with and without autism spectrum disorders. J Neurodev Disord 2:39-46|
Showing the most recent 10 out of 25 publications