Wednesday, January 28, 2026 1/28/2026

A Multimodal Imaging Study of Dopamine in Early Psychosis

Award Number: R01MH128330
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2029

Group Awards By:

View Award Description

A Multimodal Imaging Study of Dopamine in Early Psychosis - A large body of evidence suggests that abnormal striatal dopamine (DA) transmission is a key pathophysiological phenomenon in schizophrenia (SCZ), mainly within the associative striatum (AST). However, it remains unclear where striatal DA abnormalities in psychosis start and whether they can be turned into a biomarker for development of psychotic illness. Early studies in individuals at clinical high-risk for psychosis (CHR) demonstrated that patients had higher [18F]DOPA uptake (i.e., DA synthesis capacity) in the AST compared to healthy control subjects (HC). One study reported that CHR individuals who developed a syndromal psychotic disorder had higher [18F]DOPA uptake than CHR individuals who did not progress. However, more recent work in larger samples has not replicated either finding. We recently completed a feasibility study in which we used [11C]-(+)-PHNO w/methylphenidate (MPH) challenge to examine intrasynaptic DA transmission in 14 CHR individuals and 14 HCs. We found that intrasynaptic DA transmission was significantly elevated in the limbic/ventral striatum (VST), and not in any other ROI, in CHR individuals compared to HC. There was a strong correlation between intrasynaptic DA transmission in VST and total negative symptoms in the CHR group in which greater displacement was related to less negative symptoms. CHR subjects experienced no change in positive symptoms with MPH challenge, which demonstrates the safety of this technique. Additionally, our preliminary data with neuromelanin sensitive MRI (NM-MRI), a MR technique of measuring NM, a metabolite of DA, in different presynaptic nuclei (the substantia nigra [SN; the ventromedial portion of which projects to the AST] and ventral tegmental area [VTA; which projects to the VST]), demonstrate positive relationships between the contrast-to-noise ratio (CNR) of NM-MRI in the SN and positive symptoms in CHR and SCZ subjects. Taken together, these findings may reflect: 1) that striatal DA abnormalities in early psychosis progress in a temporo-spatial manner from VST to AST; 2) a clinical pattern in which negative symptoms are related to limbic DA transmission and positive symptoms reflect DA function in associative regions; 3) differences in biomarker (i.e., PHNO w/MPH challenge, NM-MRI, [18F]DOPA). This proposal will aim to advance our understanding of the nature, topography, and timing of striatal DA alterations in early psychosis by using multimodal PET/MR imaging (i.e., [11C]raclopride w/MPH challenge and NM-MRI) in the same CHR patients. We will recruit 115 CHR individuals. All subjects will undergo [11C]raclopride w/MPH and NM-MRI imaging along with clinical assessments. Patients will be followed every 3 months for two years or until conversion to psychosis, whichever comes first, to assess for conversion to psychosis and clinical outcomes. Clarifying the nature, timing, and topography of DA abnormalities in early psychosis will greatly inform translational studies and could provide support for alternative initial therapeutic interventions to prevent progression in early psychosis.


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 = $0 )
2026	2023	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	2	1/12/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	2	7/16/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	2	5/10/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $706,228 )
2023	2023	RESEARCH FOUNDATION FOR MENTAL HYGIENE INC	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	001	2	5/16/2023	NON-COMPETING CONTINUATION	$706,228
2023	2023	RESEARCH FOUNDATION FOR MENTAL HYGIENE INC	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	002	2	8/6/2023	NON-COMPETING CONTINUATION	$0
2023	2022	RESEARCH FOUNDATION FOR MENTAL HYGIENE INC	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	1	1/23/2023	NEW	$0
														Subtotal = $706,228

Issue Date FY: 2022 ( Subtotal = $742,572 )
2022	2022	RESEARCH FOUNDATION FOR MENTAL HYGIENE INC	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	1	8/8/2022	NEW	$742,572
														Subtotal = $742,572

Grand Total All Awards = $1,448,800

Top

All Categories

About

Search

Reports

Data Submission

Award Information

A Multimodal Imaging Study of Dopamine in Early Psychosis

Award Number: R01MH128330

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/15/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer