# Individualized risk prediction in persons at clinical high-risk for psychosis using neuromelanin-sensitive MRI.

> **NIH NIH R01** · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · 2020 · $634,917

## Abstract

ABSTRACT
Psychotic disorders are severe, debilitating illnesses with limited treatment options. Identification of
individuals who are at elevated risk for developing psychotic disorders is a critical first step for
prevention. Prior research has established that those individuals at clinical high risk (CHR) who go on
to develop a full-blown psychotic disorder (converters), as a group, tend to exhibit excess dopamine
in the nigro-striatal pathway, as measured by PET. But this finding is unlikely to help identify
individual subjects given its low predictive value and the practical limitations associated with PET
(e.g., radiation exposure). Previous research has also established that a combination of widely
available clinical variables –the NAPLS2 calculator– can predict risk of conversion with moderate
predictive value. Here, we propose to use neuromelanin-sensitive MRI (NM-MRI), a novel, easy-to-
acquire, non-invasive MRI technique that can be safely used in pediatric individuals and that provides
a proxy for psychosis-related nigro-striatal dopamine excess, as a predictive biomarker for risk of
conversion in CHR individuals. Furthermore, we aim to combine this objective biomarker with the
clinical (subjective) information in the NAPLS2 calculator to test whether this biomarker can improve
the accuracy of individual risk prediction beyond that achieved by clinical information alone, a critical
test of the potential clinical utility of a biomarker that previous imaging studies in CHR populations
have largely ignored. Thus, we aim to combine the strengths of an easy-to-acquire, objective MRI
biomarker tapping into the pathophysiology of psychosis and those of an established risk algorithm
based on clinical data to more accurately identify individuals at risk for developing full-blown psychotic
disorders and predict time to conversion. Specifically, and as supported by our preliminary data, we
first aim to determine whether baseline NM-MRI of the substantia nigra, pars compacta (SNc) can
reveal abnormally increased signal specifically in those CHR individuals with more severe attenuated
psychotic symptoms. Second, we aim to determine whether baseline NM-MRI SNc signal is
particularly elevated in CHR converters compared to non-converters and to sociodemographically
matched healthy controls. Third, we aim to assess whether NM-MRI SNc signal can improve the
accuracy of risk predictions over and above those derived from the NAPLS2 calculator. If successful,
this proposal will thus establish the potential clinical utility of a novel MRI biomarker that can be
adopted widely and used safely in pediatric and non-pediatric populations to enhance risk predictions
for the development of psychosis and potentially to monitor treatment and aid in personalized
treatment selection.

## Key facts

- **NIH application ID:** 9962495
- **Project number:** 5R01MH117323-03
- **Recipient organization:** NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
- **Principal Investigator:** Guillermo Horga
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $634,917
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962495

## Citation

> US National Institutes of Health, RePORTER application 9962495, Individualized risk prediction in persons at clinical high-risk for psychosis using neuromelanin-sensitive MRI. (5R01MH117323-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9962495. Licensed CC0.

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