# Preliminary imaging studies of the kappa opioid receptors in schizophrenia and their relationship to dopamine function

> **NIH NIH R21** · STATE UNIVERSITY NEW YORK STONY BROOK · 2022 · $199,375

## Abstract

Despite clinical and preclinical evidence suggesting a potential role for the kappa
dynorphin system in schizophrenia, there are no rigorous in vivo investigations of this
system in schizophrenia. We propose a multimodal imaging study to obtain information
about the availability of kappa opioid receptors (KOR) in striatum in schizophrenia and
explore its relationship to dopaminergic function measured in the same subjects, with a
neuromelanin sensitive MRI (NM-MRI) scan. We recently validated NM-MRI as a
measure of neuromelanin concentration and a marker of dopaminergic function,
demonstrating a significant relationship between NM signal in the substantia nigra and
Positron Emission Tomography measures of dopamine release capacity in the striatum. In
this proposal 10 antipsychotic-drug naïve patients with schizophrenia and 10
demographically matched healthy controls will undergo a PET scan with
[18F]LY2459989, a selective KOR antagonist radiotracer, and a NM-MRI scan to obtain
in the same subjects a measure of KOR availability in the striatum and neuromelanin in
the substantia nigra. We expect that groups will differ on both measures, and that
upregulation of KOR will relate to higher neuromelanin in patients with SCZ. This pilot
study will inform the design of a much larger study and provide POC for biomarker-
driven investigations of KOR antagonists in schizophrenia by providing in vivo
molecular measures and a link between KOR and dopamine dysfunction. This may
ultimately provide support for advancing new therapeutic testing of specific KOR
antagonists, informed by the use of potential biomarkers that we will probe here, the
KOR and NM-MRI, to enhance the design and selection of patients with schizophrenia
that could be targeted. New therapies are badly needed in this disease, particularly for
patients in whom first-line D2-based treatments do not produce full remission of
symptoms. Alternative or additional therapies to D2 drugs will improve the quality of life
for patients suffering from this devastating disease.

## Key facts

- **NIH application ID:** 10304170
- **Project number:** 5R21MH125454-02
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Anissa Abi-Dargham
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $199,375
- **Award type:** 5
- **Project period:** 2020-12-01 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10304170

## Citation

> US National Institutes of Health, RePORTER application 10304170, Preliminary imaging studies of the kappa opioid receptors in schizophrenia and their relationship to dopamine function (5R21MH125454-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10304170. Licensed CC0.

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