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Contribution of Glutamate Excess and Inflammation to Progressive White Matter Changes in Psychosis

Award Number: R01MH118484
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/02/2023
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Contribution of Glutamate Excess and Inflammation to Progressive White Matter Changes in Psychosis - Schizophrenia is a complex disorder associated with subtle white matter abnormalities that progress over time. Alterations are associated with disease severity across symptom dimensions and worse overall outcomes, but no strategies exist to attenuate white matter disease progression. This is largely because the underlying pathophysiological processes remain unknown. Glutamate excess and inflammation may be contributing factors, but we do not know if there is a period early in the illness where these affect white matter or if they alter white matter across illness stages. We propose to use multimodal neuroimaging to study 60 unmedicated first-episode psychosis patients, 60 unmedicated chronic psychosis patients, and 120 matched healthy controls. We will use (1) advanced diffusion weighted imaging to measure white matter structural integrity, (2) Magnetic Resonance Spectroscopy to measure glutamatergic and inflammatory markers in white matter, and (3) blood samples to measure peripheral inflammatory and glutamatergic markers to test the hypothesis that white matter integrity deficits increase as a function of illness stage and that glutamate excess and inflammation contribute to white matter pathology. Identification of factors that contribute to progressive white matter deficits holds the promise to transform our mechanistic understanding and inform biomarkers for targeted drug development investigating the potential of glutamatergic or anti-inflammatory agents delaying or attenuating white matter decline in schizophrenia.


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 = $0 )
2025	2023	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Mental Health Research Grants	000	6	5/26/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Mental Health Research Grants	000	5	1/22/2024	NON-COMPETING CONTINUATION	-$650,430
2024	2023	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Mental Health Research Grants	004	6	3/18/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$594,252
2024	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Mental Health Research Grants	003	5	3/18/2024	NON-COMPETING CONTINUATION	-$1
2024	2023	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Mental Health Research Grants	001	6	1/22/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$650,430
2024	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Mental Health Research Grants	002	4	3/18/2024	NON-COMPETING CONTINUATION	-$594,251
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $650,431 )
2023	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Mental Health Research Grants	001	5	6/13/2023	NON-COMPETING CONTINUATION	$650,431
2023	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Mental Health Research Grants	000	4	4/27/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $650,431

Issue Date FY: 2022 ( Subtotal = $636,324 )
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Mental Health Research Grants	000	4	7/1/2022	NON-COMPETING CONTINUATION	$636,324
														Subtotal = $636,324

Issue Date FY: 2021 ( Subtotal = $636,324 )
2021	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Mental Health Research Grants	000	3	6/20/2021	NON-COMPETING CONTINUATION	$636,324
														Subtotal = $636,324

Issue Date FY: 2020 ( Subtotal = $665,358 )
2020	2020	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Mental Health Research Grants	000	2	6/23/2020	NON-COMPETING CONTINUATION	$665,358
														Subtotal = $665,358

Issue Date FY: 2019 ( Subtotal = $684,663 )
2019	2019	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Mental Health Research Grants	000	1	8/26/2019	NEW	$684,663
2019	2019	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Mental Health Research Grants	001	1	9/25/2019	NEW	$0
														Subtotal = $684,663

Grand Total All Awards = $3,273,100

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Contribution of Glutamate Excess and Inflammation to Progressive White Matter Changes in Psychosis

Award Number: R01MH118484

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/02/2023

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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