# A Multimodal Imaging Study of Dopamine in Early Psychosis

> **NIH NIH R01** · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · 2022 · $742,572

## Abstract

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 prov...

## Key facts

- **NIH application ID:** 10522816
- **Project number:** 1R01MH128330-01A1
- **Recipient organization:** NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
- **Principal Investigator:** Ragy Ramsis Girgis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $742,572
- **Award type:** 1
- **Project period:** 2022-08-15 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10522816

## Citation

> US National Institutes of Health, RePORTER application 10522816, A Multimodal Imaging Study of Dopamine in Early Psychosis (1R01MH128330-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10522816. Licensed CC0.

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