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UC Davis MIND Institute

UC Davis MIND Institute

IDDRC SCIENTIFIC THEMES

Integrated Biobehavioral Characterization of Intellectual and Developmental Disabilities

Projects on this theme are designed to examine relationships among behaviors and their biological substrates, thereby illuminating causal pathways and suggesting avenues for prevention and treatment. These projects are noteworthy for their sophisticated multidimensional approach to characterizing behavioral endophenotypes and for their consideration of the entire causal pathway — from genes to neural systems to behavior. IDDRC efforts on this theme are led by David Amaral. Representative publications are:

Angkustsiri K, Goodlin-Jones B, Deprey L, Brahmbhatt K, Harris S, Simon TJ. Social Impairments in Chromosome 22q11.2 Deletion Syndrome (22q11.2DS): Autism Spectrum Disorder or a Different Endophenotype?  J Autism Dev Disord 2013. LINK

Braunschweig D, Duncanson P, Boyce R, Hansen R, Ashwood P, Pessah IN, Hertz-Picciotto I, Van de Water J. Behavioral correlates of maternal antibody status among children with autism. J Autism Dev Disord 2012. LINK

Nordahl CW, Braunschweig D, Iosif AM, Lee A, Rogers S, Ashwood P, Amaral DG, Van de Water J. Maternal autoantibodies are associated with abnormal brain enlargement in a subgroup of children with autism spectrum disorder. Brain Behav Immun 2013. LINK

Environmental Contributions to Intellectual and Developmental Disabilities

Projects on this theme are focused on the complex interplay of the environment, genetics, physiology, and epigenetic influences on development and the risk for autism and other neurodevelopmental disorders. Many of these projects leverage extensive phenotyping, clinical, genomic, and exposure data to identify gestational and early postnatal environmental exposures that contribute added risk to genetic load in highly susceptible populations. Other projects use in vitro mouse and human neuronal cell models to identify mechanisms by which environmental exposures alter signaling systems implicated in the etiology of neurodevelopmental disorders. IDDRC efforts on this theme are led by Isaac Pessah. Representative publications are:

Mitchell MM, Woods R, Chi LH, Schmidt RJ, Pessah IN, Kostyniak PJ, LaSalle JM. Levels of select PCB and PBDE congeners in human postmortem brain reveal possible environmental involvement in 15q11-q13 duplication autism spectrum disorder. Environ Mol Mutagen 2012. LINK

Liu J, Koscielska KA, Cao Z, Hulsizer S, Grace N, Mitchell G, Nacey C, Githinji J, McGee J, Garcia-Arocena D, Hagerman RJ, Nolta J, Pessah IN, Hagerman PJ. Signaling defects in iPSC-derived fragile X premutation neurons. Hum Mol Genet 2012. LINK

Zerbo O, Iosif AM, Walker C, Ozonoff S, Hansen RL, Hertz-Picciotto I. Is maternal influenza or fever during pregnancy associated with autism or developmental delays? Results from the CHARGE (CHildhood Autism Risks from Genetics and Environment) study. J Autism Dev Disord. 2013 Jan;43(1):25-33. LINK

Targeted Treatments for Intellectual and Developmental Disabilities

Projects on this theme are focused on ensuring that evidence-based pharmacological, behavioral, and educational treatments are therapies are available to individuals affected by neurodevelopmental disorders. These projects are designed to develop new treatments or to evaluate, compare, and refine existing treatments as well as to create methods for assessing treatment effects. IDDRC projects on this theme are also concerned with using technology to implement and disseminate treatments. IDDRC efforts on this theme are led by Sally Rogers. Representative publications are:

Berry-Kravis EM, Hessl D, Rathmell B, Zarevics P, Cherubini M, Walton-Bowen K, Mu Y, Nguyen DV, Gonzalez-Heydrich J, Wang PP, Carpenter RL, Bear MF, Hagerman RJ. Effects of STX209 (arbaclofen) on neurobehavioral function in children and adults with fragile X syndrome: a randomized, controlled, phase 2 trial. Sci Transl Med. 2012 Sep 19;4(152):152ra127. LINK

Dawson G, Jones EJ, Merkle K, Venema K, Lowy R, Faja S, Kamara D, Murias M, Greenson J, Winter J, Smith M, Rogers SJ, Webb SJ. Early behavioral intervention is associated with normalized brain activity in young children with autism. J Am Acad Child Adolesc Psychiatry. 2012 Nov;51(11):1150-9. LINK

Silverman JL, Smith DG, Rizzo SJ, Karras MN, Turner SM, Tolu SS, Bryce DK, Smith DL, Fonseca K, Ring RH, Crawley JN. Negative allosteric modulation of the mGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism. Sci Transl Med. 2012 Apr 25;4(131):131ra51. LINK

Vismara LA, Young GS, Rogers SJ. Telehealth for expanding the reach of early autism training to parents. Autism Res Treat. 2012. LINK