The Autism Spectrum Disorders (ASD) encompass a spectrum of disorders which include autism, Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS), Asperger"s disorder and Rett syndrome. The working hypothesis of this proposal is that individuals with ASD experience disturbances in the intricate interplay between genetic predisposition, environmental triggers and experience-mediated neuronal activity during a sensitive period of development, and that this leads to an altered program of gene expression. Thus the neurological disabilities that are characteristic of the disorder result from genetic variability in the processes of synaptic development, maturation, refinement, and connectivity that normally shape the brain, and from an environmental insult that perturbs normal experience-dependant synaptic development. This proposal offers a novel approach aimed at unraveling the genetic mechanisms, improving diagnosis, deciphering the interplay between environment and genetics, and developing rational approaches to therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH085143-05
Application #
8231454
Study Section
Special Emphasis Panel (ZHD1-MRG-C (16))
Program Officer
Senthil, Geetha
Project Start
2008-07-22
Project End
2013-12-31
Budget Start
2012-03-01
Budget End
2013-12-31
Support Year
5
Fiscal Year
2012
Total Cost
$710,306
Indirect Cost
$302,084
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
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
Hanson, Ellen; Cerban, Bettina M; Slater, Chelsea M et al. (2013) Brief report: prevalence of attention deficit/hyperactivity disorder among individuals with an autism spectrum disorder. J Autism Dev Disord 43:1459-64
Kong, S W; Shimizu-Motohashi, Y; Campbell, M G et al. (2013) Peripheral blood gene expression signature differentiates children with autism from unaffected siblings. Neurogenetics 14:143-52
Vardarajan, B N; Eran, A; Jung, J-Y et al. (2013) Haplotype structure enables prioritization of common markers and candidate genes in autism spectrum disorder. Transl Psychiatry 3:e262
Hanson, Ellen; Nasir, Ramzi H; Fong, Alexa et al. (2010) Cognitive and behavioral characterization of 16p11.2 deletion syndrome. J Dev Behav Pediatr 31:649-57
Liu, Hongye; Kohane, Issac S (2009) Tissue and process specific microRNA-mRNA co-expression in mammalian development and malignancy. PLoS One 4:e5436