In this project, we will develop an understanding of the range of clinical symptoms and biological factors (genetics and brain morphometry) that correlate with obsessive-compulsive behavior in autism. Autism is a highly heterogeneous disorder. A significant number of patients do not improve substantially with current treatments. We refer to this group of patients as difficult-to-treat autism (DTT-Autism). Our preliminary data suggest that these patients exhibit obsessive-compulsive behavior (OCB). We will test the central hypothesis that participants with autism with high OCB represent a subtype of difficult-to-treat autism (DTT-Autism) who will have abnormal maturation of frontal-striatal circuitry and genetic susceptibilities analogous to those previously studied in obsessive-compulsive spectrum (OCS) conditions. Capitalizing on recent progress in neuroimaging and genetics in OC spectrum (OCS) disorders, this project will test the hypothesis that autism with OCB will share genetic and brain circuitry changes that have been demonstrated in OCS disorders. We will test the hypothesis that autism with OCB will correlate with abnormalities in frontal-striatal circuitry as is true for OCD and related OCS disorders. We will also look for associations between rare and common variation in OC-related genes and OCB symptoms in autism. Using a combination of approaches including clinical assessment, neuroimaging and genotyping, we will characterize the subtype of autism with OCB. This work is important as it studies a group of autism patients who are in greatest need of treatment development. If our hypotheses about the strong biologic relationship between OC spectrum disorders and autism with OCB are accurate, novel treatments for autism may be drawn from ongoing research in interventions in treatment-refractory OCD.

Public Health Relevance

;Autism affects a large number of people in the population today and is associated with high costs to families and society. Unfortunately, a large proportion of people with autism do not respond to current treatment and this proposal seeks as a primary goal biomarkers which may predict level of function, severity and treatment response in autism.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
1P20GM103645-01A1
Application #
8465708
Study Section
Special Emphasis Panel (ZGM1-TWD-B (CB))
Project Start
Project End
Budget Start
2013-08-15
Budget End
2014-07-31
Support Year
1
Fiscal Year
2013
Total Cost
$360,826
Indirect Cost
$138,779
Name
Brown University
Department
Type
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912
Song, Joo-Hyun; B├ędard, Patrick (2015) Paradoxical benefits of dual-task contexts for visuomotor memory. Psychol Sci 26:148-58
Moher, Jeff; Sit, Jonathan; Song, Joo-Hyun (2015) Goal-directed action is automatically biased towards looming motion. Vision Res 113:188-97
Aguiar, Derek; Wong, Wendy S W; Istrail, Sorin (2014) Tumor haplotype assembly algorithms for cancer genomics. Pac Symp Biocomput :3-14
Amso, Dima; Haas, Sara; Markant, Julie (2014) An eye tracking investigation of developmental change in bottom-up attention orienting to faces in cluttered natural scenes. PLoS One 9:e85701
Pescosolido, Matthew F; Stein, David M; Schmidt, Michael et al. (2014) Genetic and phenotypic diversity of NHE6 mutations in Christianson syndrome. Ann Neurol 76:581-93
Schlesinger, Matthew; Johnson, Scott P; Amso, Dima (2014) Prediction-learning in infants as a mechanism for gaze control during object exploration. Front Psychol 5:441
Moher, Jeff; Song, Joo-Hyun (2014) Perceptual decision processes flexibly adapt to avoid change-of-mind motor costs. J Vis 14:1
Amso, Dima; Haas, Sara; Tenenbaum, Elena et al. (2014) Bottom-up attention orienting in young children with autism. J Autism Dev Disord 44:664-73
Corbett, Jennifer E; Song, Joo-Hyun (2014) Statistical extraction affects visually guided action. Vis cogn 22:881-895
McLean, Rebecca L; Johnson Harrison, Ashley; Zimak, Eric et al. (2014) Executive function in probands with autism with average IQ and their unaffected first-degree relatives. J Am Acad Child Adolesc Psychiatry 53:1001-9

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