The present application seeks funding to establish an Intellectual and Developmental Disabilities Research Center (IDDRC) at the University of California, which will be fully integrated into, and benefit from, the existing resources of the UC Davis MIND Institute and its campus partners. The MIND Institute is an integrated program that is internationally recognized for ground-breaking studies of autism, fragile X syndrome, and other IDD conditions. The proposed IDDRC includes three components. First, we propose a research component that addresses the focus area of Multi-Modal Treatment Approaches. This component includes a clinical trial targeting children with fragile X syndrome that combines a drug (lovastatin) with a parent-implemented intervention. Novel outcome measures focusing on language and challenging behavior will evaluate efficacy. The clinical trial will be accompanied by studies focused on FMRI-related signaling pathways so as to illuminate the mechanisms by which treatment achieves its effects and to identify biomarkers that indicate treatment efficacy and individual differences in response to treatment. Second, we propose for inclusion 56 IDD-related projects funded by NIH and other federal and private sources. Ten of the projects are funded by NICHD. These projects address three scientific themes: Integrated Biobehavioral Characterization of IDD, Environmental Contributions to IDD, and Treatments for IDD. Third, we propose core components to facilitate interdisciplinary, translational research in IDD. The cores include an Administrative Core and a Clinical Translational Core, with the latter focused on recruitment and diagnostic characterization of human participants. The remaining cores will provide assays of immune function, cellular and molecular biology and imaging, and environmental contaminants (Biological Analysis Core);measures of complex human behavior, particularly for establishing endophenotypes (Neurobehavioral Analysis Core);assays of rodent behavior for evaluating mutant rodent models and supporting preclinical evaluations of drug safety and efficacy (Rodent Behavior Core);and the management and analysis of complex multidimensional data derived from human and animal studies (Biostatistics, Bioinformatics, and Research Design).

Public Health Relevance

The proposed IDDRC is designed to support a translational science agenda focused on IDD. The IDDRC will integrate research from multiple disciplines and bridge basic and clinical science to arrive at treatments for IDD conditions. The range of IDD conditions include autism spectrum disorder, fragile X syndrome, Down syndrome, ADHD, chromosome 22q11.2 deletion syndrome, and many others.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HD079125-02
Application #
8740539
Study Section
Special Emphasis Panel (ZHD1-DSR-H (50))
Program Officer
Parisi, Melissa
Project Start
2013-09-24
Project End
2018-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
2
Fiscal Year
2014
Total Cost
$1,246,354
Indirect Cost
$437,033
Name
University of California Davis
Department
Psychiatry
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Kazdoba, Tatiana M; Leach, Prescott T; Yang, Mu et al. (2016) Translational Mouse Models of Autism: Advancing Toward Pharmacological Therapeutics. Curr Top Behav Neurosci 28:1-52
Leach, Prescott T; Hayes, Jane; Pride, Michael et al. (2016) Normal Performance of Fmr1 Mice on a Touchscreen Delayed Nonmatching to Position Working Memory Task. eNeuro 3:
Napoli, Eleonora; Song, Gyu; Schneider, Andrea et al. (2016) Warburg effect linked to cognitive-executive deficits in FMR1 premutation. FASEB J 30:3334-3351
Horiuchi, Makoto; Smith, Lucas; Maezawa, Izumi et al. (2016) CX3CR1 ablation ameliorates motor and respiratory dysfunctions and improves survival of a Rett syndrome mouse model. Brain Behav Immun :
Loveall, Susan J; Channell, Marie Moore; Phillips, B Allyson et al. (2016) Receptive vocabulary analysis in Down syndrome. Res Dev Disabil 55:161-72
Pearson, Brandon L; Crawley, Jacqueline N; Eilam, David et al. (2016) Curiosity as an approach to ethoexperimental analysis: Behavioral neuroscience as seen by students and colleagues of Bob Blanchard. Neurosci Biobehav Rev :
Dunaway, Keith W; Islam, M Saharul; Coulson, Rochelle L et al. (2016) Cumulative Impact of Polychlorinated Biphenyl and Large Chromosomal Duplications on DNA Methylation, Chromatin, and Expression of Autism Candidate Genes. Cell Rep 17:3035-3048
Jones, K L; Croen, L A; Yoshida, C K et al. (2016) Autism with intellectual disability is associated with increased levels of maternal cytokines and chemokines during gestation. Mol Psychiatry :
McDuffie, Andrea; Machalicek, Wendy; Bullard, Lauren et al. (2016) A Spoken-Language Intervention for School-Aged Boys With Fragile X Syndrome. Am J Intellect Dev Disabil 121:236-65
Klusek, Jessica; McGrath, Sara E; Abbeduto, Leonard et al. (2016) Pragmatic Language Features of Mothers With the FMR1 Premutation Are Associated With the Language Outcomes of Adolescents and Young Adults With Fragile X Syndrome. J Speech Lang Hear Res 59:49-61

Showing the most recent 10 out of 62 publications