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Reward, impulsive sensation seeking and emotional dysregulation: neural mechanisms underlying risk for bipolar disorder in young adults

Award Number: R37MH100041
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2024
PERIOD OF PERFORMANCE END DATE: 12/31/2028

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Reward, impulsive sensation seeking and emotional dysregulation: neural mechanisms underlying risk for bipolar disorder in young adults - Bipolar Disorder (BD) is often misdiagnosed as Major Depressive Disorder (MDD) and poorly-treated. As risk for mental health problems increases in young adulthood, identifying objective neural marker predictors of future BD vs. MDD in young adults will provide neural markers for early risk identification and neural targets for new interventions to delay or prevent these debilitating disorders. The goal in the initial MERIT Award period was to adopt a transdiagnostic and dimensional approach to identify neural marker correlates and predictors of worsening manic/hypomanic vs. depressive symptoms in young adults, ultimately to distinguish BD from MDD risk. We showed that: elevated reward expectancy-related left ventrolateral prefrontal cortical (vlPFC) and prediction error-related left ventral striatal activity, lower PE-related right amygdala activity, and lower bilateral cingulum bundle fractional anisotropy (FA), a measure of white matter fiber collinearity, predicted current and/or future mania/hypomania; greater largescale (central executive [CEN], salience and default mode) network functional connectivity (FC) and greater CEN dorsolateral prefrontal cortical (dlPFC) activity during emotional regulation predicted current and future depression; while lower right uncinate fasciculus FA and greater left vlPFC and lower left inferior temporal cortical thickness were associated with greater mania/hypomania and depression. In the proposed MERIT extension, to yield robust neural markers of BD vs. MDD risk, we aim to examine: 1. an independent young adult sample (n=150 non mood disordered 18-30 year-olds) to test findings; 2. higher temporal resolution neural, and dopamine transmission, measures using fMRI-based source-localized electroencephalography (EEG) beta power/FC and midbrain neuromelanin contrast to noise ratio; 3. longitudinal neuroimaging to identify neural change predictors of worsening mania/hypomania and depression, and ultimately BD and MDD; 4. relationships among neural measures, response tendencies and symptom trajectories predisposing to BD and MDD, to better understand risk pathways for these disorders; and 5. young adults with 1st and/ or 2nd degree relatives with BD and MDD/ MDD, given their higher BD and MDD risk. RELEVANCE (See instructions): Bipolar Disorder (BD) is often misdiagnosed as Major Depressive Disorder (MDD). The proposed MERIT extension aims to study a new sample of young adults at familial risk of BD and/or MDD using more sensitive measures of brain activity and repeated brain scans, to test present findings, identify robust brain markers of BD vs. MDD risk, improve early BD risk identification, and aid new treatment development.


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: 2026 ( Subtotal = $731,051 )
2026	2026	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	000	13	2/6/2026	NON-COMPETING CONTINUATION	$731,051
														Subtotal = $731,051

Issue Date FY: 2025 ( Subtotal = $620,868 )
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	12	1/8/2025	NON-COMPETING CONTINUATION	$620,868
2025	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	001	10	2/20/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $620,868

Issue Date FY: 2024 ( Subtotal = $745,928 )
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	11	12/13/2023	EXTENSION WITH OR WITHOUT FUNDS	$0
2024	2024	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	002	11	5/1/2024	EXTENSION WITH OR WITHOUT FUNDS	$74,592
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	11	11/17/2023	EXTENSION WITH OR WITHOUT FUNDS	$671,336
														Subtotal = $745,928

Issue Date FY: 2023 ( Subtotal = $699,195 )
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	10	1/16/2023	NON-COMPETING CONTINUATION	$699,195
														Subtotal = $699,195

Issue Date FY: 2022 ( Subtotal = $690,548 )
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	000	9	12/17/2021	NON-COMPETING CONTINUATION	$621,493
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	001	9	6/26/2022	NON-COMPETING CONTINUATION	$69,055
														Subtotal = $690,548

Issue Date FY: 2021 ( Subtotal = $705,261 )
2021	2021	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	001	8	4/21/2021	NON-COMPETING CONTINUATION	$70,526
2021	2021	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Mental Health Research Grants	000	8	12/14/2020	NON-COMPETING CONTINUATION	$634,735
														Subtotal = $705,261

Issue Date FY: 2020 ( Subtotal = $716,525 )
2020	2020	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Mental Health Research Grants	000	7	12/19/2019	NON-COMPETING CONTINUATION	$644,873
2020	2020	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Mental Health Research Grants	001	7	3/11/2020	NON-COMPETING CONTINUATION	$71,652
														Subtotal = $716,525

Issue Date FY: 2019 ( Subtotal = $935,183 )
2019	2019	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Mental Health Research Grants	001	6	5/28/2019	COMPETING CONTINUATION	$58,874
2019	2019	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Mental Health Research Grants	000	6	2/28/2019	COMPETING CONTINUATION	$762,103
2019	2019	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Mental Health Research Grants	002	6	8/20/2019	SUPPLEMENT FOR EXPANSION	$114,206
														Subtotal = $935,183

Grand Total All Awards = $5,844,559

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Reward, impulsive sensation seeking and emotional dysregulation: neural mechanisms underlying risk for bipolar disorder in young adults

Award Number: R37MH100041

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/01/2024

PERIOD OF PERFORMANCE END DATE: 12/31/2028

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