The UIC ACE will focus over the next 5 years on the genetics, neurobiology, cognitive and affective processes, and pharmacology of insistence on sameness (IS) in autism spectrum disorders (ASD). A large sample of children with self-reported autism spectrum disorder will be screened by the Assessment Core for further screening by administration of the ADI-R to the parents. Profanes meeting ADI-R criteria for autistic disorder will be recruited for further study if they are also classified by the ADI-R IS items as high (N=150) or low IS (N=100). In addition, high IS subjects will need to score 15 or more on the sum of two IS factors on the RBS-R to avoid floor effects for the pharmacogenetic trial. These 250 subjects will all be included in project I, Genetics of Serotonin in Autism: Neurochemical and Clinical Endophenotypes, along with 225 previously studied subjects and their parents for a total of 475 trios. This project will study 25 serotonin- related genes for association with autism and with IS more specifically. Resequencing of strong candidate genes will be conducted with all of the subjects in the pharmacogenetic project (III) and with the low IS subjects in project II. In addition, the 250 subjects will have serotonin measures collected for analysis with genetic and phenotype measures. In Project II: Translational Studies of Cognitive, Affective and Neurochemical Processes Underlying Insistence on Sameness in Autism, fMRI studies of IS will be conducted on 50 high IS subjects also in Project III, 50 low IS subjects (also in Project I) and 50 control subjects. In addition, rat studies in which parallel behavioral and neurochemical approaches will be used. Project III: The Pharmacogenetics of Treatment for Insistence on Sameness in Autism has been designed to replicate and extend a preliminary study of escitalopram treatment of IS related irritability in ASD. Project IV: Autism-Associated Serotonin Transporter (SERT) Mutations will provide characterization of mutations previously found to be associated with high IS behaviors in subjects with autism. The UIC ACE is an exciting center that brings together experts in a diverse set of disciplines to comprehensively study IS, one of the two cardinal features described by Kanner in 1943.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center (P50)
Project #
5P50HD055751-05
Application #
8129551
Study Section
Special Emphasis Panel (ZHD1-MRG-C (16))
Program Officer
Kau, Alice S
Project Start
2007-08-06
Project End
2014-07-31
Budget Start
2011-08-01
Budget End
2014-07-31
Support Year
5
Fiscal Year
2011
Total Cost
$1,891,889
Indirect Cost
Name
University of Illinois at Chicago
Department
Psychiatry
Type
Schools of Medicine
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612
Chen, Rui; Davis, Lea K; Guter, Stephen et al. (2017) Leveraging blood serotonin as an endophenotype to identify de novo and rare variants involved in autism. Mol Autism 8:14
Shuffrey, Lauren C; Guter, Stephen J; Delaney, Shannon et al. (2017) Is there sexual dimorphism of hyperserotonemia in autism spectrum disorder? Autism Res 10:1417-1423
Sagar, Angela; Pinto, Dalila; Najjar, Fedra et al. (2017) De novo unbalanced translocation (4p duplication/8p deletion) in a patient with autism, OCD, and overgrowth syndrome. Am J Med Genet A 173:1656-1662
Amodeo, Dionisio A; Grospe, Gena; Zang, Hui et al. (2017) Cognitive flexibility impairment and reduced frontal cortex BDNF expression in the ouabain model of mania. Neuroscience 345:229-242
Schmitt, Lauren M; White, Stormi P; Cook, Edwin H et al. (2017) Cognitive mechanisms of inhibitory control deficits in autism spectrum disorder. J Child Psychol Psychiatry :
Amodeo, D A; Rivera, E; Cook Jr, E H et al. (2017) 5HT2A receptor blockade in dorsomedial striatum reduces repetitive behaviors in BTBR mice. Genes Brain Behav 16:342-351
Syed, Anam; Baker, Phillip M; Ragozzino, Michael E (2016) Pedunculopontine tegmental nucleus lesions impair probabilistic reversal learning by reducing sensitivity to positive reward feedback. Neurobiol Learn Mem 131:1-8
Francis, Sunday M; Kistner-Griffin, Emily; Yan, Zhongyu et al. (2016) Variants in Adjacent Oxytocin/Vasopressin Gene Region and Associations with ASD Diagnosis and Other Autism Related Endophenotypes. Front Neurosci 10:195
Francis, Sunday M; Kim, Soo-Jeong; Kistner-Griffin, Emily et al. (2016) ASD and Genetic Associations with Receptors for Oxytocin and Vasopressin-AVPR1A, AVPR1B, and OXTR. Front Neurosci 10:516
Yan, Qi; Chen, Rui; Sutcliffe, James S et al. (2016) The impact of genotype calling errors on family-based studies. Sci Rep 6:28323

Showing the most recent 10 out of 86 publications