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Neuroimaging Studies of Reward Processing in Depression

Award Number: R37MH068376
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2022
PERIOD OF PERFORMANCE END DATE: 02/28/2027

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Neuroimaging Studies of Reward Processing in Depression - Major Depressive Disorder (MDD) remains a major public health problem with poorly understood etiology and pathophysiology. Impairment in reward processing and anhedonia are core features of MDD. Findings during the prior award period have shown that MDD and anhedonic phenotypes are characterized by functional, structural and molecular abnormalities within a CorticoStriatal Valuation Circuit critically implicated in value encoding and reinforcement learning. The main goal of the this R37 renewal is to expand this line of work in several fundamental new directions to (1) attain a better mechanistic understanding of MDD and anhedonia by focusing on a novel target - Nociceptin/Orphanin FQ Receptors - expected to yield molecular abnormalities associated with CorticoStriatal Valuation Circuit and stress- induced inflammatory abnormalities (Aims 1 and 2); and (2) identify abnormalities that map disease course (Aim 3). This will be achieved through an innovative integration of (1) molecular imaging techniques with a novel positron emission tomography (PET) NOP tracer ([11C]NOP1A) in unmedicated individuals with current or past MDD, (2) state-of-the-art analyses of stress-related pro-inflammatory transcription control pathways, (3) behavioral and functional neuroimaging markers of key depressive phenotypes, and (4) a naturalistic follow-up design. To differentiate between state- and trait-like markers of vulnerability, currently depressed individuals (MDD), remitted individuals with a history of MDD (rMDD), and never-depressed healthy controls will be included. Based on findings from the prior project period, we hypothesize that, relative to healthy controls, MDD and rMDD participants will show significantly higher [11C]NOP1A binding potential in brain regions critically implicated in stress regulation and reward processing (Hypotheses 1). Moreover, among individuals with current or past MDD, N/OFQ abnormalities in brain regions implicated in stress regulation and reward processing will be associated with (1) behavioral and neural markers of anhedonic phenotypes; (2) lower ability to regulate stress responses; and (3) higher stress-related proinflammatory cytokines and transcription control pathways (Hypotheses 2). Finally, we expect that N/OFQ abnormalities (and associated behavioral, fMRI, hormonal, and inflammatory markers) will predict anhedonic symptoms and poorer general functioning at follow-up (Hypothesis 3). Collectively, the proposed research promises to improve our mechanistic understanding of stress-induced anhedonia and the pathophysiology of MDD, as well as our ability to identify mechanisms that prospectively predict reward deficit-related symptoms, thus opening novel avenues for improved treatment and prevention.


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 = $649,636 )
2025	2025	THE MCLEAN HOSPITAL CORPORATION	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Mental Health Research Grants	000	20	2/19/2025	NON-COMPETING CONTINUATION	$649,636
														Subtotal = $649,636

Issue Date FY: 2024 ( Subtotal = $761,816 )
2024	2024	THE MCLEAN HOSPITAL CORPORATION	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Mental Health Research Grants	001	19	7/18/2024	NON-COMPETING CONTINUATION	$76,182
2024	2024	THE MCLEAN HOSPITAL CORPORATION	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Mental Health Research Grants	000	19	2/16/2024	NON-COMPETING CONTINUATION	$685,634
														Subtotal = $761,816

Issue Date FY: 2023 ( Subtotal = $761,816 )
2023	2023	MCLEAN HOSPITAL CORPORATION, THE	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Mental Health Research Grants	000	18	4/19/2023	NON-COMPETING CONTINUATION	$761,816
														Subtotal = $761,816

Issue Date FY: 2022 ( Subtotal = $785,591 )
2022	2022	MCLEAN HOSPITAL CORPORATION, THE	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Mental Health Research Grants	000	17	8/1/2022	EXTENSION WITH OR WITHOUT FUNDS	$785,591
2022	2020	MCLEAN HOSPITAL CORPORATION, THE	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Mental Health Research Grants	001	16	8/25/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $785,591

Issue Date FY: 2020 ( Subtotal = $736,833 )
2020	2020	MCLEAN HOSPITAL CORPORATION, THE	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Mental Health Research Grants	000	16	3/18/2020	NON-COMPETING CONTINUATION	$736,833
														Subtotal = $736,833

Issue Date FY: 2019 ( Subtotal = $738,677 )
2019	2019	MCLEAN HOSPITAL CORPORATION, THE	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Mental Health Research Grants	000	15	3/6/2019	NON-COMPETING CONTINUATION	$738,677
														Subtotal = $738,677

Issue Date FY: 2018 ( Subtotal = $738,677 )
2018	2018	MCLEAN HOSPITAL CORPORATION, THE	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Mental Health Research Grants	001	14	6/15/2018	NON-COMPETING CONTINUATION	$73,869
2018	2018	MCLEAN HOSPITAL CORPORATION, THE	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Mental Health Research Grants	000	14	2/7/2018	NON-COMPETING CONTINUATION	$664,808
														Subtotal = $738,677

Issue Date FY: 2017 ( Subtotal = $737,867 )
2017	2017	MCLEAN HOSPITAL CORPORATION, THE	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Mental Health Research Grants	000	13	3/1/2017	NON-COMPETING CONTINUATION	$664,079
2017	2017	MCLEAN HOSPITAL CORPORATION, THE	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Mental Health Research Grants	001	13	7/17/2017	NON-COMPETING CONTINUATION	$73,788
														Subtotal = $737,867

Issue Date FY: 2016 ( Subtotal = $734,474 )
2016	2016	MCLEAN HOSPITAL	115 MILL STREET	BELMONT	MA	02478	MIDDLESEX	USA	Mental Health Research Grants	000	12	4/25/2016	COMPETING CONTINUATION	$734,474
														Subtotal = $734,474

Grand Total All Awards = $6,645,387

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Neuroimaging Studies of Reward Processing in Depression

Award Number: R37MH068376

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2022

PERIOD OF PERFORMANCE END DATE: 02/28/2027

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