Obsessive compulsive disorder (OCD) is a common and disabling psychiatric illness that is often refractory to available treatments. The onset of OCD during childhood and adolescence suggests that atypical brain maturation may underlie the disorder, and mandates the study of pediatric patients to define a """"""""developmental window"""""""" at which therapeutic interventions may be directed to abort progression to chronic illness. To probe the mechanisms of neurobehavioral development relevant to pediatric OCD, the Candidate has begun work in functional magnetic resonance imaging (fMRI) and child psychiatry. Addressing the need for additional skill acquisition, a 5-year career development plan will provide an essential grounding in 1) pediatric neuroimaging, 2) developmental neuroscience, and 3) clinical research skills. Career development will be shaped by a research project designed to extend preliminary findings of cortico-striatal-pallidalthalamic (CSPT) involvement in pediatric OCD by testing for hypothesized maturational abnormalities of CSPT function and structure in young patients. Hyperactive response of CSPT elements - the rostral anterior cingulate cortex, posterior medial frontal cortex, and dorsolateral prefrontal cortex - occurs in adult OCD when patients commit errors on simple cognitive tasks. In addition, excessive white matter connectivity within CSPT circuitry has been demonstrated in adult OCD, and could be driven by hyperactivity of CSPT functions, such as the response to errors. In the proposed study, error-processing function and white matter coherence of CSPT circuitry will be studied across prepubertal, pubertal and adolescent stages of development to begin to elucidate how CSPT abnormalities emerge and progress during the early course of OCD. Outstanding departmental support;collective expertise in fMRI, pediatric OCD, cognitive-emotional development, and clinical research;and, opportunities for future translational research make the University of Michigan an ideal environment for this award.

Public Health Relevance

OCD affects millions of American children, and understanding the abnormalities of brain maturation associated with early onset illness will help to foster improved understanding, treatment, and eventually, prevention of this disabling condition.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23MH082176-04
Application #
8088144
Study Section
Developmental Brain Disorders Study Section (DBD)
Program Officer
Friedman-Hill, Stacia
Project Start
2008-09-24
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
4
Fiscal Year
2011
Total Cost
$180,360
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Psychiatry
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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Fitzgerald, Kate D; Taylor, Stephan F (2015) Error-processing abnormalities in pediatric anxiety and obsessive compulsive disorders. CNS Spectr 20:346-54
Fitzgerald, Kate D; Liu, Yanni; Reamer, Elyse N et al. (2014) Atypical frontal-striatal-thalamic circuit white matter development in pediatric obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry 53:1225-33, 1233.e1-9
Liu, Yanni; Hanna, Gregory L; Carrasco, Melisa et al. (2014) Altered relationship between electrophysiological response to errors and gray matter volumes in an extended network for error-processing in pediatric obsessive-compulsive disorder. Hum Brain Mapp 35:1143-53
Carrasco, Melisa; Hong, Christina; Nienhuis, Jenna K et al. (2013) Increased error-related brain activity in youth with obsessive-compulsive disorder and other anxiety disorders. Neurosci Lett 541:214-8
Fitzgerald, Kate D; Liu, Yanni; Stern, Emily R et al. (2013) Reduced error-related activation of dorsolateral prefrontal cortex across pediatric anxiety disorders. J Am Acad Child Adolesc Psychiatry 52:1183-1191.e1
Perkins, Suzanne C; Welsh, Robert C; Stern, Emily R et al. (2013) Topographic analysis of the development of individual activation patterns during performance monitoring in medial frontal cortex. Dev Cogn Neurosci 6:137-48
Kim, Kamin; Carp, Joshua; Fitzgerald, Kate D et al. (2013) Neural congruency effects in the multi-source interference task vanish in healthy youth after controlling for conditional differences in mean RT. PLoS One 8:e60710
Carrasco, Melisa; Harbin, Shannon M; Nienhuis, Jenna K et al. (2013) Increased error-related brain activity in youth with obsessive-compulsive disorder and unaffected siblings. Depress Anxiety 30:39-46
Stern, Emily R; Welsh, Robert C; Gonzalez, Richard et al. (2013) Subjective uncertainty and limbic hyperactivation in obsessive-compulsive disorder. Hum Brain Mapp 34:1956-70

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