Bipolar disorder (BPD) in a major source of morbidity and mortality for adults in America, with more than $24 billion spent annually;however, far less is known about BPD in children and adolescents. Emerging data shows that BPD children are impaired in reversal learning. This process requires behavioral adaptation to changing stimulus-reward contingencies and engages the ventral prefrontal cortex (vPFC), ventral striatum, and amygdala. My long-term goal is to understand how brain/behavior interactions, central to emotion regulation, differentiate normal from psychiatrically ill children, in order to develop more effective diagnostic and treatment strategies. The study of reversal learning will facilitate my efforts in this respect. The objectives of this application are to (1) acquire training in fMRI methods and experimental design, (2) identify neurological correlates of impaired reversal learning in pediatric BPD, and (3) develop an R01 application based on this work. My central hypothesis is that BPD children have specific impairments in reversal learning due to dysfunction in a neural circuit encompassing the vPFC, ventral striatum, and amygdala. To test this hypothesis, I will: (1) use fMRI to identify substrates of reversal learning in normal children;(2) determine functional neuroanatomical and behavioral differences in BPD children during reversal learning;(3) evaluate the specificity of reversal learning deficits in psychiatric controls. I will use the """"""""response reversal"""""""" task developed by our group to evaluate reversal learning with 3 Tesla fMRI and behavioral data. This will be among the first studies to link behavioral dysfunction to brain abnormalities in children with strictly defined BPD. From these studies, I expect to determine that BPD children have selective alterations in fronto-temporal structures during reversal learning. The proposed work will positively impact child mental health advancing our knowledge of the underlying brain/behavior abnormalities mediating BPD in children and adolescents. In turn, greater pathophysiological understanding of pediatric BPD will move the field of pediatric BPD beyond symptom-based diagnosis, potentially allowing more accurate or earlier diagnosis, thus reducing the morbidity and mortality in children and adolescents suffering from this debilitating disorder.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Career Transition Award (K22)
Project #
3K22MH074945-02S1
Application #
7871008
Study Section
Special Emphasis Panel (ZMH1-ERB-P (01))
Program Officer
Sesma, Michael A
Project Start
2009-07-01
Project End
2010-06-30
Budget Start
2009-07-01
Budget End
2010-06-30
Support Year
2
Fiscal Year
2009
Total Cost
$203,921
Indirect Cost
Name
Emma Pendleton Bradley Hospital
Department
Type
DUNS #
075706176
City
East Providence
State
RI
Country
United States
Zip Code
02915
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Goldstein, Benjamin I; Strober, Michael; Axelson, David et al. (2013) Predictors of first-onset substance use disorders during the prospective course of bipolar spectrum disorders in adolescents. J Am Acad Child Adolesc Psychiatry 52:1026-37
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