This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Autism represents one of the most severe disorders of development, yet its biological underpinnings remain unknown. Although the prevalence of autism in the general population is estimated at 0.05 -- 0.1 percent, a variety of studies indicate that deficits in social functioning and communication affect 15 percent of first-degree relatives of autistic individuals. The poor long-term outcomes seen in such children underscores the need for a better understanding of the biological mechanisms involved in autism. Three intersecting domains of behavior: communication, social reciprocity and restricted/repetitive behaviors, taken together are diagnostic of the illness, but appear partially independent. This fact, in concert with evidence from genome-wide linkage investigations and candidate gene studies, provides evidence that a single etiology of autism is unlikely. Given the heterogeneous nature of autism, identification of homogeneous subgroups is essential to furthering our understanding o f the biology underlying the behaviors associated with this disorder. The availability of noninvasive, non-radioactive neuroimaging techniques and sophisticated data analytic approaches used in combination with family genetic data holds the promise of greatly improving our ability to identify these subgroups. The principal goal of the work proposed in this project is to use these tools to identify neuromorphometric and neurochemical measures that define meaningful endophenotypes in autism. In addition, the extent to which these measures are shared among siblings and therefore are familial will be explored as a means of identifying these endophenotypes. Using these tools, Affected Sibling Pairs selected from the Autism Genetic Resource Exchange multiplex families, and a sample of non-autistic control children selected from an ongoing study of normal children at UCLA will be examined. The CAN/AGRE study population is a large group of multiplex families with phenotypic and genotype data a vailable for access by research scientists. We propose that key behavioral phenotypic dimensions of autism including: delay of language onset, repetitive/stereotyped behaviors and social reciprocity, are associated with specific brain neuromorphometric and neurochemical measures. Furthermore, we will examine the extent to which the neurobiologic findings underlying these phenotypic variations will be correlated among siblings, suggesting that they may be useful phenotypes for future investigations. Taken together, these studies will provide the basis for genetic studies to delineate specific gene brain behavioral pathways and lay the foundation for early detection and better intervention in autism.
| Green, Shulamite A; Hernandez, Leanna M; Bowman, Hilary C et al. (2018) Sensory over-responsivity and social cognition in ASD: Effects of aversive sensory stimuli and attentional modulation on neural responses to social cues. Dev Cogn Neurosci 29:127-139 |
| Yang, Yaling; Joshi, Shantanu H; Jahanshad, Neda et al. (2017) Neural correlates of proactive and reactive aggression in adolescent twins. Aggress Behav 43:230-240 |
| Dennis, Emily L; Rashid, Faisal; Faskowitz, Josh et al. (2017) MAPPING AGE EFFECTS ALONG FIBER TRACTS IN YOUNG ADULTS. Proc IEEE Int Symp Biomed Imaging 2017:101-104 |
| Walsh, Christine M; Ruoff, Leslie; Walker, Kathleen et al. (2017) Sleepless Night and Day, the Plight of Progressive Supranuclear Palsy. Sleep 40: |
| Green, Shulamite A; Hernandez, Leanna; Bookheimer, Susan Y et al. (2017) Reduced modulation of thalamocortical connectivity during exposure to sensory stimuli in ASD. Autism Res 10:801-809 |
| Kodumuri, Nishanth; Sebastian, Rajani; Davis, Cameron et al. (2016) The association of insular stroke with lesion volume. Neuroimage Clin 11:41-45 |
| Kamins, Joshua; Giza, Christopher C (2016) Concussion-Mild Traumatic Brain Injury: Recoverable Injury with Potential for Serious Sequelae. Neurosurg Clin N Am 27:441-52 |
| Agis, Daniel; Goggins, Maria B; Oishi, Kumiko et al. (2016) Picturing the Size and Site of Stroke With an Expanded National Institutes of Health Stroke Scale. Stroke 47:1459-65 |
| Levine, Andrew J; Soontornniyomkij, Virawudh; Achim, Cristian L et al. (2016) Multilevel analysis of neuropathogenesis of neurocognitive impairment in HIV. J Neurovirol 22:431-41 |
| Flournoy, John C; Pfeifer, Jennifer H; Moore, William E et al. (2016) Neural Reactivity to Emotional Faces May Mediate the Relationship Between Childhood Empathy and Adolescent Prosocial Behavior. Child Dev 87:1691-1702 |
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