The Course and Outcome of Bipolar Disorders in Youth (COBY) study has comprehensively characterized the clinical course of a large sample of youth with bipolar disorder (BD), and has identified demographic and clinical factors that are associated with different illness courses. To date, however, COBY has not included neuroimaging assessments. Including such assessments now will allow, for the first time, an evaluation of the impact of 13-year course of BD and treatment upon neural circuitry function and structure. Furthermore, the majority of COBY participants are currently between 18-30 years old, when the brain, and prefrontal cortex in particular, continues to develop. Including neuroimaging assessments in COBY participants now can thus take advantage of the neurodevelopmental processes occurring between 18-30 years where there are unique opportunities to intervene therapeutically to help normalize abnormalities in neural functioning and structure. Focusing on this age range will also provide a critically important opportunity to determine the extent to which neuroimaging measures predict future clinical course in adulthood. Having normal prefrontal cortical function and structure may predict better clinical course in adulthood, even in COBY participants with poor clinical course in youth, and may lead to decisions to reduce, or even stop, specific treatments in these individuals. In the proposed study, we will determine how previous BD clinical course (e.g., % time with mood symptoms vs. euthymic; % time with comorbid disorders) and treatment exposure from childhood into adulthood impacts neural circuitry functioning and structure supporting key NIMH RDoC information processing domains, and compare neuroimaging findings in COBY participants with those of demographically-matched healthy controls (Aim 1). We will also determine whether neuroimaging measures predict illness course in adulthood, beyond demographic and clinical factors, and previous clinical course in youth (Aim 2). We will use machine learning to explore patterns of wholebrain functioning, white and gray matter structure, and clinical and demographic measures, that most accurately predict future clinical course at the individual subject level. The proposed study also provides a valuable opportunity to inform the field regarding the clinical and functional course and outcome from youth into adulthood in a large, well-characterized sample of people with BD. This is important because the clinical outcome of BD youth in adulthood remains uncertain, as only two studies with a total of 72 subjects followed BD youth into their early twenties. Structural and functional neuroimaging techniques will be employed in a representative subsample of COBY participants (n=120), and healthy controls (n=50). Comprehensive assessments of psychopathology and functioning will be collected at the time of neuroimaging, and twice more during the proposed project period in the 120 COBY participants. This proposal accords with the NIMH's mission to define developmental trajectories of mental disorders and develop strategies to better define risk and protective factors for disease trajectories across the lifespan, and with the RDoC initiative.

Public Health Relevance

The aim of the proposed study is to identify the impact of long-term previous clinical course and treatment on the brain in individuals with childhood-onset bipolar disorder, and examine how these changes in the brain influence future clinical course during adulthood. The participants are currently between 18-30 years old when the brain begins to achieve full maturity. Thus, this study will provide a unique opportunity to determine the extent to which neuroimaging measures predict future clinical course during an important neurodevelopmental period in individuals with bipolar disorder and can yield findings that will aid treatment decisions for these individuals.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH059929-18
Application #
9428459
Study Section
Child Psychopathology and Developmental Disabilities Study Section (CPDD)
Program Officer
Friedman-Hill, Stacia
Project Start
2000-08-01
Project End
2021-02-28
Budget Start
2018-03-01
Budget End
2019-02-28
Support Year
18
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Van Meter, Anna; Goldstein, Benjamin I; Goldstein, Tina R et al. (2018) Parsing cyclothymic disorder and other specified bipolar spectrum disorders in youth. J Affect Disord 238:375-382
Birmaher, Boris; Merranko, John A; Goldstein, Tina R et al. (2018) A Risk Calculator to Predict the Individual Risk of Conversion From Subthreshold Bipolar Symptoms to Bipolar Disorder I or II in Youth. J Am Acad Child Adolesc Psychiatry 57:755-763.e4
Krantz, Megan; Goldstein, Tina; Rooks, Brian et al. (2018) Sexual Risk Behavior Among Youth With Bipolar Disorder: Identifying Demographic and Clinical Risk Factors. J Am Acad Child Adolesc Psychiatry 57:118-124
MacPherson, Heather A; Ruggieri, Amanda L; Christensen, Rachel E et al. (2018) Developmental evaluation of family functioning deficits in youths and young adults with childhood-onset bipolar disorder. J Affect Disord 235:574-582
Frías, Álvaro; Dickstein, Daniel P; Merranko, John et al. (2017) Longitudinal cognitive trajectories and associated clinical variables in youth with bipolar disorder. Bipolar Disord 19:273-284
Angulo, Melina; Rooks, Brian T; Gill, MaryKay et al. (2017) Psychometrics of the screen for adult anxiety related disorders (SCAARED)- A new scale for the assessment of DSM-5 anxiety disorders. Psychiatry Res 253:84-90
Yen, S; Stout, R; Hower, H et al. (2016) The influence of comorbid disorders on the episodicity of bipolar disorder in youth. Acta Psychiatr Scand 133:324-34
Birmaher, Boris (2016) The Risks of Persistent Irritability. J Am Acad Child Adolesc Psychiatry 55:538-9
Borue, Xenia; Mazefsky, Carla; Rooks, Brian T et al. (2016) Longitudinal Course of Bipolar Disorder in Youth With High-Functioning Autism Spectrum Disorder. J Am Acad Child Adolesc Psychiatry 55:1064-1072.e6
Eckstrand, Kristen L; Travis, Michael John; Forbes, Erika E et al. (2016) Sex Differences and Personalized Psychiatric Care. Biol Psychiatry 80:e81-e83

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