Pediatric bipolar disorder (PBD) is increasingly recognized, poorly understood, and ineffectively treated. With newly available fMRI technology, the field has matured for use in children to examine underlying brain dysfunction and treatment effects in PBD. There are very few investigators in the field trained to integrate clinical trials with fMRI methods. This career (K23) award will permit the candidate to develop as an independent clinical investigator to fill this void. The project described below serves as a medium to learn new skills under the mentorship of active, senior clinical investigators and will also allow her to take part in didactic training by protecting her time for these activities. The proposal reflects the need to bring a multidisciplinary approach to clinical research, particularly in the area of pediatric psychiatric research. Thus, the plan emphasizes pharmacotherapy, clinical trial methodology, statistics, ethics, and brain imaging using fMRI. The plan includes regular supervision by her primary mentors, interactions with internal and external-consultants and attendance at relevant didactic courses. Drs. Janicak and Sweeney will be the primary mentors. The study described in this application will examine treatment effects on the disturbances of affective circuitry hypothesized to underlie PBD. Specifically, the central aim is to conduct a double-blind, randomized clinical trial to test the hypothesis that the novel antipsychotic, risperidone, will have a rapid onset of action and efficacy at least comparable to divalproex sodium in the treatment of mixed and manic episodes of PBD. A pilot study, using a subset of subjects, will investigate whether activity in the amygdala and prefrontal cortex (PFC) underlies dysfunction in the affective circuitry of PBD and whether effective treatment normalizes any aberrant activity. During five years, 40 outpatient subjects with PBD manic or mixed episodes, ages 8-17 years, referred to the UI Pediatric Mood Disorder Clinic will be recruited.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23RR018638-03
Application #
6911720
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Wilde, David B
Project Start
2003-08-15
Project End
2008-07-31
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
3
Fiscal Year
2005
Total Cost
$147,366
Indirect Cost
Name
University of Illinois at Chicago
Department
Psychiatry
Type
Schools of Medicine
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612
Passarotti, Alessandra M; Fitzgerald, Jacklynn M; Sweeney, John A et al. (2013) Negative emotion interference during a synonym matching task in pediatric bipolar disorder with and without attention deficit hyperactivity disorder. J Int Neuropsychol Soc 19:601-12
Schenkel, L S; Passarotti, A M; Sweeney, J A et al. (2012) Negative emotion impairs working memory in pediatric patients with bipolar disorder type I. Psychol Med 42:2567-77
Schenkel, Lindsay S; West, Amy E; Jacobs, Rachel et al. (2012) Cognitive dysfunction is worse among pediatric patients with bipolar disorder Type I than Type II. J Child Psychol Psychiatry 53:775-81
Pavuluri, Mani N; Ellis, James A; Wegbreit, Ezra et al. (2012) Pharmacotherapy impacts functional connectivity among affective circuits during response inhibition in pediatric mania. Behav Brain Res 226:493-503
Pavuluri, Mani N; Passarotti, Alessandra M; Fitzgerald, Jacklynn M et al. (2012) Risperidone and divalproex differentially engage the fronto-striato-temporal circuitry in pediatric mania: a pharmacological functional magnetic resonance imaging study. J Am Acad Child Adolesc Psychiatry 51:157-170.e5
Passarotti, Alessandra M; Ellis, James; Wegbreit, Ezra et al. (2012) Reduced functional connectivity of prefrontal regions and amygdala within affect and working memory networks in pediatric bipolar disorder. Brain Connect 2:320-34
Lu, Lisa H; Zhou, Xiaohong Joe; Fitzgerald, Jacklynn et al. (2012) Microstructural abnormalities of white matter differentiate pediatric and adult-onset bipolar disorder. Bipolar Disord 14:597-606
Wegbreit, Ezra; Ellis, James A; Nandam, Aneesh et al. (2011) Amygdala functional connectivity predicts pharmacotherapy outcome in pediatric bipolar disorder. Brain Connect 1:411-22
Pavuluri, Mani N; Passarotti, Alessandra M; Lu, Lisa H et al. (2011) Double-blind randomized trial of risperidone versus divalproex in pediatric bipolar disorder: fMRI outcomes. Psychiatry Res 193:28-37
Jacobs, Rachel H; Pavuluri, Mani N; Schenkel, Lindsay S et al. (2011) Negative emotion impacts memory for verbal discourse in pediatric bipolar disorder. Bipolar Disord 13:287-93

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