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From Manic Symptoms to Bipolar Disorder: Neural-behavioral Markers Using Two Analytic Models

Award Number: R01MH121451
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2020
PERIOD OF PERFORMANCE END DATE: 01/31/2026

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From Manic Symptoms to Bipolar Disorder: Neural-behavioral Markers Using Two Analytic Models - PROJECT SUMMARY -No change from the original submission Bipolar disorder (BD) is a devastating neuropsychiatric illness that affects 2-5% of youth and causes morbidity, functional impairment, and suicide. Prodromal manic symptoms without manic episodes usually emerge before BD types I and II (BD-I/II) develop, but less than 60% of youth with manic symptoms will develop BD-I/II. The uncertainty of diagnosis and illness progression results in potentially detrimental interventions and 7-10 years delay appropriate treatments. It is thus imperative that objective biomarkers of risk for conversion to BD-I/II are identified and tested in youth before the peak onset of illness. Given that neural measures of structure and function associated with emotion and reward processing, in combination with clinical and behavior measures, can improve prediction of psychiatric outcomes in youth, this project will investigate brain-behavior relations in the most severely ill youth during inpatient stays and aims to build a predictive model of BD. We aim to use two distinct analytic models to test our hypotheses. First a general linear model (GLM) with a machine learning (ML) model of regularized regression with cross validation and second a whole brain ML pattern recognition model. We will first identify neural and behavioral markers of BD-I/II in circuitry associated with emotion and reward processing. We hypothesize that decreased activity and connectivity in prefrontal, amygdala, and striatal regions and behavioral measures showing less sleep, lower activity, and poorer mood and cognition will distinguish BDI/II from clinically matched youth without mania and healthy. Next, we will identify using ML a whole brain neural classifier of BD-I/II relative to clinically matched inpatients without mania. Aim 2 is to, after two years, identify and quantify the neural and behavioral measures that predict conversion to BD-I/II, and to test individual conversion in an independent group of high symptomatic risk adolescents. Aim 3 is to identify brain-behavior associations for app development. Training samples include mid-/post- pubertal adolescents aged 13-17 years recruited from the nation’s only specialized inpatient unit for adolescents with BD and the general adolescent unit at our hospital; 70 well-characterized adolescents with BD-I/II, a clinically matched group of 70 inpatient youth without mania. Testing sample is an independent group of 180 adolescents with manic symptoms without BD-I/II. 60 healthy controls will be recruited. The project includes emotion and reward processing neural function and structure, clinical and behavioral measures including sleep and activity with actigraphy, computerized cognitive measures, and self-reports during inpatient evaluation and for two weeks post discharge. At two-year follow up, clinical assessments will confirm diagnoses. This is the first study to employ a multimodal assessment of behavior and mood symptoms combined with multimodal imaging methods to comprehensively assess disease-specific abnormalities and prediction of BD-I/II. Findings from this study may identify biological and behavioral markers of conversion to BD-I/II in adolescents and may contribute developing disease-specific risk calculators, low-cost biosensors for mobile applications, and novel targets of intervention.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $139,176 )
2025	2025	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	000	5	1/7/2025	SUPPLEMENT FOR EXPANSION	$139,176
														Subtotal = $139,176

Issue Date FY: 2024 ( Subtotal = $665,224 )
2024	2024	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	000	5	1/12/2024	NON-COMPETING CONTINUATION	$598,702
2024	2024	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	001	5	8/14/2024	NON-COMPETING CONTINUATION	$66,522
														Subtotal = $665,224

Issue Date FY: 2023 ( Subtotal = $676,763 )
2023	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	000	4	2/22/2023	NON-COMPETING CONTINUATION	$676,763
														Subtotal = $676,763

Issue Date FY: 2022 ( Subtotal = $685,934 )
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	000	3	2/9/2022	NON-COMPETING CONTINUATION	$617,339
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	001	3	5/23/2022	NON-COMPETING CONTINUATION	$68,595
														Subtotal = $685,934

Issue Date FY: 2021 ( Subtotal = $695,997 )
2021	2021	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Mental Health Research Grants	000	2	2/11/2021	NON-COMPETING CONTINUATION	$695,997
														Subtotal = $695,997

Issue Date FY: 2020 ( Subtotal = $741,587 )
2020	2020	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Mental Health Research Grants	000	1	2/28/2020	NEW	$741,587
														Subtotal = $741,587

Grand Total All Awards = $3,604,681

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From Manic Symptoms to Bipolar Disorder: Neural-behavioral Markers Using Two Analytic Models

Award Number: R01MH121451

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/01/2020

PERIOD OF PERFORMANCE END DATE: 01/31/2026

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