The career development and research plans outlined in this Mentored Patient-Oriented Research Career Development Award application are designed to enable the candidate to independently design and conduct neuroimaging studies investigating the neurobiology of autism by examining increased brain size and the involvement of the cerebelo-thalamo-frontal circuit in the pathophysiology of this neurodevelopment disorder. Autism is a severe disorder characterized by marked social and communication deficits, restricted and stereotyped patterns of behaviors and interests. A wide range of abnormalities has been reported and studies of brain structure have implicated several aspects of brain development involved in neuronal organization including the elaboration of dendritic and axonal ramifications, the establishments of synaptic connection, and cell death. Recent neuropathologic and neuroimaging studies have reported increased brain size in autism, and evidence supporting the underdevelopment of the circuitry of neural networks that involve cerebral cortex, limbic system and cerebellum. The proposed longitudinal study will use the combination of volumetric measurements obtained from magnetic resonance imaging scans and chemical shift imaging proton spectroscopy obtained at 30 months intervals from a group of children with autism (8-12 years of age) and individually-matched controls to characterize the developmental changes of brain enlargement, and the involvement of the cerebello-thalamo-frontal circuit in autism. It will also provide the candidate with the experience necessary to apply advanced neuroimaging techniques and a solid foundation from which to conduct longitudinal studies investigating the developmental neurobiology of autism and possibly identifying clinical, prognostic and therapeutic correlates. The candidate is certified in psychiatry, and child and adolescent psychiatry with four years of post-graduate clinical experience. Drs. Nancy Minshew, and Matchery Keshavan will serve as preceptors. Course work and directed reading in biostatistcs, data management, research ethics, neuroanatorny, neuroimaging and developmental neuroscience will complement the research training.

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-BDCN-5 (01))
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Boyce, Cheryl A
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University of Pittsburgh
Schools of Medicine
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Hardan, Antonio Y; Fung, Lawrence K; Frazier, Thomas et al. (2016) A proton spectroscopy study of white matter in children with autism. Prog Neuropsychopharmacol Biol Psychiatry 66:48-53
Jou, Roger J; Frazier, Thomas W; Keshavan, Matcheri S et al. (2013) A two-year longitudinal pilot MRI study of the brainstem in autism. Behav Brain Res 251:163-7
Frazier, Thomas W; Keshavan, Matcheri S; Minshew, Nancy J et al. (2012) A two-year longitudinal MRI study of the corpus callosum in autism. J Autism Dev Disord 42:2312-22
Jou, Roger J; Mateljevic, Natasa; Minshew, Nancy J et al. (2011) Reduced central white matter volume in autism: implications for long-range connectivity. Psychiatry Clin Neurosci 65:98-101
Uddin, Lucina Q; Menon, Vinod; Young, Christina B et al. (2011) Multivariate searchlight classification of structural magnetic resonance imaging in children and adolescents with autism. Biol Psychiatry 70:833-41
Jou, Roger J; Minshew, Nancy J; Keshavan, Matcheri S et al. (2010) Cortical gyrification in autistic and Asperger disorders: a preliminary magnetic resonance imaging study. J Child Neurol 25:1462-7
Jou, Roger J; Minshew, Nancy J; Keshavan, Matcheri S et al. (2010) Enlarged right superior temporal gyrus in children and adolescents with autism. Brain Res 1360:205-12
Griebling, Jessica; Minshew, Nancy J; Bodner, Kimberly et al. (2010) Dorsolateral prefrontal cortex magnetic resonance imaging measurements and cognitive performance in autism. J Child Neurol 25:856-63
Hardan, Antonio Y; Libove, Robin A; Keshavan, Matcheri S et al. (2009) A preliminary longitudinal magnetic resonance imaging study of brain volume and cortical thickness in autism. Biol Psychiatry 66:320-6
Hardan, Antonio Y; Pabalan, Melissa; Gupta, Nidhi et al. (2009) Corpus callosum volume in children with autism. Psychiatry Res 174:57-61

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