The immediate goals of this application include: training the candidate to become an independent clinical- researcher, and to addressing the brain (and genetic) basis of a cardinal, but neglected restricted, repetitive symptoms of autism spectrum disorders (ASD). Long term goals include: developing a model for integrative research, informing our understanding of the causes of ASD, and advancing our ability to test and target treatments for ASD. The research project uses well established neuroscience methods (functional MRI and genotyping) to investigate brain regions and genes involved in restricted, repetitive behavior and interest symptoms in ASD. Cognitive flexibility serves as a window into this symptom cluster, and the proposed studies address a limitation of past work by carefully parsing flexibility into its core components in children with ASD. Children with and without ASD will be genotyped for a serotonin transporter gene implicated in both ASD and cognitive flexibility and will participate in functional MRI and psychological batteries that assess cognitive flexibility and ASD symptoms. Children with ASD and the risk allele for the serotonin transporter gene are predicted to make more errors on flexibility tasks and show greater deviance in the structure and function of brain regions activated. The career development plan includes cross-disciplinary training in advanced MRI techniques, neuroanatomy, neurobiology, genetics, neuropsychology, and imaging genomics;training comes from formal didactics, directed readings and laboratoryexperiences with a distinguished panel of expert co-mentors with a neurologist as lead mentor. Research environment: The candidate's main training and research will occur in a burgeoning, collaborative autism research program at Children's National Medical Center and Georgetown University, and he will receive in-depth advanced training from established institutional and personal collaborations with scientists at the Children's Hospital of Philadelphia and Stanford University.

Public Health Relevance

According to the Center for Disease Control, 1 in 150 children in the US has autism. Repetitive behaviors and rigid, inflexible thinking are cardinal symptoms of the disorder and prevent many otherwise high funcitoning people from being poductive members of main stream society. Yet our understanding of these symptoms remains limited at cognitive, brain, and genetic levels of analysis. The proposed work seeks to define neural and genetic contributors to this cluster of autism symptoms in order to help us pursue the causes of, and target interventions to treat, these core autism deficits.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Mentored Patient-Oriented Research Career Development Award (K23)
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Special Emphasis Panel (ZRG1-BBBP-R (05))
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Gilotty, Lisa
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Children's Hospital of Philadelphia
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Yerys, Benjamin E; Herrington, John D (2014) Multimodal imaging in autism: an early review of comprehensive neural circuit characterization. Curr Psychiatry Rep 16:496
Rosenthal, Michael; Wallace, Gregory L; Lawson, Rachel et al. (2013) Impairments in real-world executive function increase from childhood to adolescence in autism spectrum disorders. Neuropsychology 27:13-8
Yerys, Benjamin E; Ruiz, Ericka; Strang, John et al. (2013) Modulation of attentional blink with emotional faces in typical development and in autism spectrum disorders. J Child Psychol Psychiatry 54:636-43
Yerys, Benjamin E; Kenworthy, Lauren; Jankowski, Kathryn F et al. (2013) Separate components of emotional go/no-go performance relate to autism versus attention symptoms in children with autism. Neuropsychology 27:537-45
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Kenworthy, Lauren; Yerys, Benjamin E; Weinblatt, Rachel et al. (2013) Motor demands impact speed of information processing in autism spectrum disorders. Neuropsychology 27:529-36
Yerys, Benjamin E; Pennington, Bruce F (2011) How do we establish a biological marker for a behaviorally defined disorder? Autism as a test case. Autism Res 4:239-41