Differences in pragmatic (i.e., social) language are the language deficit most robustly associated with Autism Spectrum Disorder (ASD) and the Broad Autism Phenotype (BAP, a constellation of subclinical features in relatives that parallel in quality the defining characteristics of ASD and are believed to reflect genetic liability in clinically unaffected relatives). Findings from the initial award period indicate that retrospective, longitudinal measures of childhood language and cognitive development in parents, together with our battery of psycholinguistic and computational linguistic measures of pragmatic ability, measurable in individuals with ASD and their parents, are highly promising markers of ASD endophenotypes that can be targeted in genetic, neurobiological and treatment studies. This competing renewal builds significantly on these findings and our related work, in three important ways. First, given striking findings that parents' early rates of language and cognitive growth in childhood predict the BAP in adulthood, and ASD severity in the next generation (i.e., their children), we expand our study design and methods significantly, to investigate a unique and more expansive archival database of retrospective developmental, cognitive, social, behavior and personality measures available on a cohort of grandparents and parents of individuals with ASD, from high school through young adult years. These rich resources, together with our existing longitudinal data on parents' grade school testing records (which we will continue to collect), will afford an unprecedented look at developmental profiles through childhood and young adulthood (prior to having a child with ASD) that may predict genetic risk of ASD. We also further investigate the biological basis of our candidate pragmatic language endophenotypes through analysis of auditory brainstem response related to an expanded battery of pragmatic language in ASD families. Finally, we investigate the molecular basis of these candidate endophenotypes in families of individuals with ASD through measurement of the Fragile X Mental Retardation Protein, which is the protein product of FMR1 (implicated in ASD symptomatology), with strong connections to the auditory brainstem, and which preliminary data show may relate to pragmatic language features in family members of individuals with ASD.

Public Health Relevance

This project investigates multigenerational developmental, behavioral, and neural markers of risk to Autism Spectrum Disorder (ASD), and molecular genetic correlates. This research takes an important step toward pinpointing different neurobiological and molecular-genetic factors associated with the social-communicative impairments in ASD in particular, and with ASD risk more generally, with key implications for better understanding of etiology and the development of targeted interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC010191-11
Application #
9993119
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Cooper, Judith
Project Start
2010-02-01
Project End
2021-08-31
Budget Start
2020-09-01
Budget End
2021-08-31
Support Year
11
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Other Health Professions
Type
Schools of Arts and Sciences
DUNS #
160079455
City
Chicago
State
IL
Country
United States
Zip Code
60611
Nayar, Kritika; Gordon, Peter C; Martin, Gary E et al. (2018) Links between looking and speaking in autism and first-degree relatives: insights into the expression of genetic liability to autism. Mol Autism 9:51
Barstein, Jamie; Martin, Gary E; Lee, Michelle et al. (2018) A Duck Wearing Boots?! Pragmatic Language Strategies for Repairing Communication Breakdowns Across Genetically Based Neurodevelopmental Disabilities. J Speech Lang Hear Res 61:1440-1454
Lee, Michelle; Martin, Gary E; Hogan, Abigail et al. (2018) What's the story? A computational analysis of narrative competence in autism. Autism 22:335-344
Losh, Molly; Martin, Gary E; Lee, Michelle et al. (2017) Developmental Markers of Genetic Liability to Autism in Parents: A Longitudinal, Multigenerational Study. J Autism Dev Disord 47:834-845
Martin, Gary E; Barstein, Jamie; Hornickel, Jane et al. (2017) Signaling of noncomprehension in communication breakdowns in fragile X syndrome, Down syndrome, and autism spectrum disorder. J Commun Disord 65:22-34
Lee, Michelle; Bush, Lauren; Martin, Gary E et al. (2017) A Multi-Method Investigation of Pragmatic Development in Individuals With Down Syndrome. Am J Intellect Dev Disabil 122:289-309
Hall, Deborah A; Robertson, Erin; Shelton, Annie L et al. (2016) Update on the Clinical, Radiographic, and Neurobehavioral Manifestations in FXTAS and FMR1 Premutation Carriers. Cerebellum 15:578-86
Klusek, Jessica; Roberts, Jane E; Losh, Molly (2015) Cardiac autonomic regulation in autism and Fragile X syndrome: a review. Psychol Bull 141:141-75
Smith, Matthew J; Fleming, Michael F; Wright, Michael A et al. (2015) Brief report: vocational outcomes for young adults with autism spectrum disorders at six months after virtual reality job interview training. J Autism Dev Disord 45:3364-9
Klusek, J; Martin, G E; Losh, M (2014) Consistency between research and clinical diagnoses of autism among boys and girls with fragile X syndrome. J Intellect Disabil Res 58:940-52

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