The proposed project focuses on a study of adolescents with bipolar spectrum disorders (i.e., bipolar I, bipolar II, or bipolar NOS disorder), a spectrum of debilitating mental illnesses that lead to widespread impairments in functioning. Given recent research that suggests that more than 60% of adults with bipolar disorders experience first onset of their illness prior to age 18, adolescents with bipolar disorders are an important population to investigate. The proposed project has three objectives: 1) characterizing abnormalities in responses to and processing of reward information, a proposed core dysfunction, in adolescents with bipolar disorders;2) identifying most sensitive predictors of prospective bipolar episode course and bipolar symptoms in adolescence;and finally, 3) confirming that multiple indices of reward processing abnormalities are tapping into a single system given theoretical models that propose bipolar disorders'core dysregulation to be in behavioral approach system (BAS), a system functioning to respond to environmental rewards. In order to accomplish the first objective, the proposed project will examine reward sensitivity and reward information processing in adolescents with bipolar disorders and in healthy adolescents, using a set of behavioral tasks, self-report measures, and measures of reward-relevant brain activity as indexed by electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). In order to accomplish the second objective, the proposed project will assess prospective bipolar symptoms and episodes during a one-year follow-up and examine which indices of reward sensitivity (i.e., self-report, behavioral, EEG, or fMRI) are the most sensitive predictors of bipolar symptom severity. Finally, in order to accomplish the third objective, multi-method indices of reward sensitivity (i.e., self-report, behavioral, EEG, fMRI) will be analyzed using structural equation modeling to determine whether they tap into a single, latent construct. The proposed project has a potential to shed light on biological and psychological mechanisms driving bipolar symptoms in adolescence. It also has a potential to provide clinical tools for identifying risk factors for worsening course of bipolar disorders and identifying patients in urgent need of aggressive early intervention. Thus, the proposed project fits with the NIMH's larger mission to investigate causes of mental illness and to understand mental illness trajectories in order to treat mental illness effectively. Candidate's career goals and training plan. Dr. Snezana Urosevic's long-term career goal is to study behavioral activation/approach system (BAS) dysfunction in bipolar spectrum disorders, with specific emphasis on development of this BAS dysfunction across the life span.
She aims to use multitude of psychosocial, behavioral, and neural indices of BAS functioning to understand the bipolar disorders'BAS dysregulation, a proposed core vulnerability in bipolar disorders. Dr. Urosevic aims to secure a tenure-track faculty position within the next 5 years, which would allow her to pursue these career research goals. In order to accomplish these long-term goals, Dr. Urosevic's immediate career development objectives are: 1) to gain expertise in research on adolescents with bipolar disorders, thus expanding her current research background with adult bipolar disorder populations;2) to gain expertise in functional magnetic resonance imaging (fMRI), expanding the repertoire of methods for assessing neural correlates of BAS functioning in bipolar disorders;3) to gain expertise in structural equation modeling, which would allow her to empirically assess relationship among various indices of BAS functioning in bipolar disorders;and 4) to develop into an independent investigator through increasing her publications record, obtaining a tenure-track faculty position, and applying for a R-01 grant. The proposed K-award will provide crucial mentorship and training, in order for Dr. Urosevic to meet these immediate career development goals. Her K-award training plan includes coursework in relevant topics (e.g., hands-on workshops on fMRI, structural equation modeling), attendance and presentations at appropriate international and national research meetings (e.g., Human Brain Mapping, International Conference on Bipolar Disorder), and extensive collaborations with her mentor, Monica Luciana, Ph.D., and co-mentors, Drs. Kathleen Thomas, Robert Krueger, Eric Youngstrom, and Jonathan Jensen. This mentoring team has a set of expertise that neatly fit with Dr. Urosevic's immediate career development goals. Dr. Luciana is an expert in adolescent neurobehavioral development in healthy and mentally ill populations, as well as in studying indices of BAS-relevant dopaminergic functioning. This is coupled with Dr. Younstrom's extensive experience in research on assessment and phenomenology of pediatric bipolar disorders and Dr. Jensen's clinical experience with assessment and treatment of pediatric bipolar disorders. In addition, Dr. Thomas has expertise in fMRI research on pediatric populations and in assessing reward processing in minors using fMRI, and Dr. Krueger has expertise in structural equation modeling in clinical psychology research. In summary, the proposed K-award promises to provide important scientific insights into adolescent bipolar disorders, as well as to launch the candidate's, Dr. Urosevic's, independent research career.

Public Health Relevance

Bipolar disorder has been proposed to be the fifth leading cause of years lived with disability of all physical and mental illnesses in the world (WHO, 2001). According to a recent study, majority of adults with bipolar disorders experience first onset prior to age 18 (Beesdo et al., 2009), but very little is known about causes of bipolar illness in children and adolescence. The proposed project's focus on understanding brain and behavioral processes leading to bipolar symptoms in adolescence has a potential to inform future interventions and reduce both individual suffering and society's cost stemming from bipolar disorder disability.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Scientist Development Award - Research & Training (K01)
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Child Psychopathology and Developmental Disabilities Study Section (CPDD)
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Sarampote, Christopher S
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University of Minnesota Twin Cities
Schools of Arts and Sciences
United States
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Uroševi?, Snežana; Collins, Paul; Muetzel, Ryan et al. (2014) Pubertal status associations with reward and threat sensitivities and subcortical brain volumes during adolescence. Brain Cogn 89:15-26