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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
7K23MH086111-03
Application #
8245811
Study Section
Special Emphasis Panel (ZRG1-BBBP-R (05))
Program Officer
Gilotty, Lisa
Project Start
2010-06-16
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2014-03-31
Support Year
3
Fiscal Year
2012
Total Cost
$132,748
Indirect Cost
$9,833
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Yerys, Benjamin E; Nissley-Tsiopinis, Jenelle; de Marchena, Ashley et al. (2016) Evaluation of the ADHD Rating Scale in Youth with Autism. J Autism Dev Disord :
Antezana, Ligia; Mosner, Maya G; Troiani, Vanessa et al. (2016) Social-Emotional Inhibition of Return in Children with Autism Spectrum Disorder Versus Typical Development. J Autism Dev Disord 46:1236-46
Pugliese, Cara E; Kenworthy, Lauren; Bal, Vanessa Hus et al. (2015) Replication and Comparison of the Newly Proposed ADOS-2, Module 4 Algorithm in ASD Without ID: A Multi-site Study. J Autism Dev Disord 45:3919-31
Yerys, Benjamin E; Gordon, Evan M; Abrams, Danielle N et al. (2015) Default mode network segregation and social deficits in autism spectrum disorder: Evidence from non-medicated children. Neuroimage Clin 9:223-32
Yerys, Benjamin E; Antezana, Ligia; Weinblatt, Rachel et al. (2015) Neural Correlates of Set-Shifting in Children With Autism. Autism Res 8:386-97
Sepeta, Leigh N; Croft, Louise J; Zimmaro, Lauren A et al. (2015) Reduced language connectivity in pediatric epilepsy. Epilepsia 56:273-82
Green, Adam E; Kenworthy, Lauren; Mosner, Maya G et al. (2014) Abstract analogical reasoning in high-functioning children with autism spectrum disorders. Autism Res 7:677-86
Yerys, Benjamin E; Herrington, John D (2014) Multimodal imaging in autism: an early review of comprehensive neural circuit characterization. Curr Psychiatry Rep 16:496
Supekar, Kaustubh; Uddin, Lucina Q; Khouzam, Amirah et al. (2013) Brain hyperconnectivity in children with autism and its links to social deficits. Cell Rep 5:738-47
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

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