This is the renewal of the Bipolar Offspring Study (BIOS; NIMH #60952). In line with the current NIMH Strategic Plan, BIOS has been investigating the additive effects of dimensional/categorical psychopathology, circadian/sleep, cognitive, environmental, and biological factors associated with the development of mood disorders in offspring of parents with bipolar disorder (BD). BIOS recruited 509 offspring from BD parents (OBP) and 353 Offspring from Control Parents (OCP) and interviewed them blind to parental diagnoses with a comprehensive battery of instruments every other year since 2001, with 92% retention. Also, in a subsample of offspring, neuroimaging tests were performed. During the next funding period, most of the sample will be entering adulthood, a time when mood disorders peak, important life changes occur (e.g., marriage, work, children), and prefrontal systems reach final stages of development. We therefore propose to continue to study the BIOS sample to identify the clinical and psychosocial trajectories from childhood into adulthood, how these trajectories change during adulthood, and the prodromal symptoms of BD. In addition, in a BIOS subsample we aim to continue to identify RDoC domain-related biomarkers of neurodevelopmental trajectories underlying positive and negative emotion processing, reward, attentional control of emotion during emotion regulation, and executive function, and the demographic, familial, neural circuitry, and environmental factors that are predictors of psychopathology and resilience. To do this, we propose to: 1) continue following the entire BIOS sample; 2) perform a second scan and neurocognitive tests for the subsamples of OBP without BD (n=35) and OCP (n=35) with prior neuroimaging /neurocognitive data; 3) complete two scans and neurocognitive tests in 35 healthy youth offspring of healthy parents; and 4) for the first time in BIOS, include two scans and neurocognitive tests in 35 OBP who developed BD. We hypothesize that distinct RDoC domain-related patterns of function and white matter structure in emotion processing, reward, and emotion regulation neural circuitries are present in OBP, and to a lesser extent, in OCP. These patterns of neural circuitry function and structure, together with environmental factors (e.g., stressors), are associated with longitudinal trajectories manifested by increased dimensional psychopathology (e.g., subsyndromal mood symptoms, mood lability, sleep problems). The presence of dimensional psychopathology then increases the risk to develop mood and other disorders (e.g., anxiety, substance abuse), and psychosocial impairment. Recurrent subsyndromal manic and depressive episodes, irritability, mood lability and/or sleep disturbances will specifically increae risk for BD. Using this framework, we propose to characterize the clinical and psychosocial functioning trajectories into adulthood and determine the specific neural circuitry and environmental factors associated with increased risk for psychopathology, especially BD, and factors associated with resilience. Such findings will facilitate prompt diagnosis and intervention thus preventing, or at least ameliorating, the negative effects of BD in youth.

Public Health Relevance

Bipolar disorder (BD) is a severe illness associated with considerable negative consequences for the normal development of the child, and increased risk for suicide and substance abuse. However, little is known about the initial symptoms and the progression of bipolar disorder from childhood to adulthood. The findings from this large study will help to identify the initial symptoms and brain biological markers related to the increased risk for developing bipolar disorder. Such findings will advance the field so that prompt diagnosis and interventions are made, thus preventing, or at least ameliorating, the negative effects of this severe and debilitating illness.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH060952-19
Application #
9697234
Study Section
Child Psychopathology and Developmental Disabilities Study Section (CPDD)
Program Officer
Friedman-Hill, Stacia
Project Start
1999-12-01
Project End
2021-05-31
Budget Start
2019-07-17
Budget End
2020-05-31
Support Year
19
Fiscal Year
2019
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
15260
Versace, A; Ladouceur, C D; Graur, S et al. (2018) Diffusion imaging markers of bipolar versus general psychopathology risk in youth at-risk. Neuropsychopharmacology 43:2212-2220
Hafeman, Danella M; Chase, Henry W; Monk, Kelly et al. (2018) Intrinsic functional connectivity correlates of person-level risk for bipolar disorder in offspring of affected parents. Neuropsychopharmacology :
Acuff, Heather E; Versace, Amelia; Bertocci, Michele A et al. (2018) Association of Neuroimaging Measures of Emotion Processing and Regulation Neural Circuitries With Symptoms of Bipolar Disorder in Offspring at Risk for Bipolar Disorder. JAMA Psychiatry 75:1241-1251
Hafeman, Danella M; Merranko, John; Goldstein, Tina R et al. (2017) Assessment of a Person-Level Risk Calculator to Predict New-Onset Bipolar Spectrum Disorder in Youth at Familial Risk. JAMA Psychiatry 74:841-847
Levenson, Jessica C; Soehner, Adriane; Rooks, Brian et al. (2017) Longitudinal sleep phenotypes among offspring of bipolar parents and community controls. J Affect Disord 215:30-36
Pan, Lisa A; Goldstein, Tina R; Rooks, Brian T et al. (2017) The Relationship Between Stressful Life Events and Axis I Diagnoses Among Adolescent Offspring of Probands With Bipolar and Non-Bipolar Psychiatric Disorders and Healthy Controls: The Pittsburgh Bipolar Offspring Study (BIOS). J Clin Psychiatry 78:e234-e243
Diler, Rasim Somer; Goldstein, Tina R; Hafeman, Danella et al. (2017) Characteristics of depression among offspring at high and low familial risk of bipolar disorder. Bipolar Disord 19:344-352
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
Wise, T; Radua, J; Via, E et al. (2017) Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: evidence from voxel-based meta-analysis. Mol Psychiatry 22:1455-1463
Mesman, Esther; Birmaher, Boris B; Goldstein, Benjamin I et al. (2016) Categorical and dimensional psychopathology in Dutch and US offspring of parents with bipolar disorder: A preliminary cross-national comparison. J Affect Disord 205:95-102

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