# Neuroimaging of the Biological Correlates of Early Psychosis: A MR-PET Study

> **NIH NIH K01** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $177,736

## Abstract

Project Summary
 In the resubmission of this K01 application, we propose to conduct a hybrid cross-sectional and
longitudinal multi-modal neuroimaging study aimed at understanding the biological nature and time
course of an acute brain response previously observed in first-episode schizophrenia patients. The acute
brain response, characterized by a global increase in extracellular free water in first-episode patients, has been
previously linked to neuroinflammation. Recent evidence suggests that the acute brain response may be part of
a compensatory immune-related action related to recovery or resiliency. In this proposal, we suggest and
investigate the hypothesis that this compensatory response may be related to the increased expression of Group
I subtype metabotropic glutamate receptor 5 (mGluR5), which have been shown to serve a beneficial
immunomodulatory role in the central nervous system. The central scientific goal of this K01 proposal is to
utilize a comprehensive data collection paradigm to 1) understand the biological nature and trajectory of the
acute brain response in early psychosis by investigating its connection to mGluR5 and 2) investigate the
hypothesis that these markers of cerebral immune activation in FEP are linked to resiliency. To achieve this goal,
we will leverage the state-of-the-art, simultaneous collection of structural, diffusion, and positron emission
tomography (PET) images utilizing the mGluR5 radioligand [18F] FPEB. With our hybrid, cross-sectional and
longitudinal study design, we will collect multi-modal imaging, blood, neurocognitive, and clinical data
from a cohort of first-episode patients and healthy matched controls. We hypothesize that patients with
greater acute brain responses and mGluR5 expression will exhibit less structural damage and better clinical and
cognitive performance after 6 months. This will be the first study to investigate the role of mGluR5 in early
psychosis and the results of this pilot study will be valuable for gaining a greater understanding of the
neurobiological components underlying resiliency after illness onset.
 To carry out the proposed scientific aims, I identified four principal areas of training and associated
mentors/advisors: 1) PET image acquisition and analysis under the mentorship of Dr. Jacob Hooker (primary
mentor) and advisors Drs. Julie Price and Ciprian Catana; 2) clinical and neurocognitive assessments under
the mentorship of Dr. William Stone (co-mentor) and advisor Dr. Matcheri Keshavan; 3) biostatistics with
advisor Dr. Mark Vangel; 4) professional development under the mentorship of Dr. Marek Kubicki (co-mentor).
This project will take place at multiple institutions within Harvard Medical School, which, combined, create an
ideal environment for the execution of the scientific aims and proposed training plan. Upon completion of this
K01, I will have acquired the expertise to become an independent researcher and the preliminary data for a
future R01.

## Key facts

- **NIH application ID:** 10460419
- **Project number:** 5K01MH115247-05
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** AMANDA ELLIS LYALL
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $177,736
- **Award type:** 5
- **Project period:** 2018-08-01 → 2024-01-05

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10460419

## Citation

> US National Institutes of Health, RePORTER application 10460419, Neuroimaging of the Biological Correlates of Early Psychosis: A MR-PET Study (5K01MH115247-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10460419. Licensed CC0.

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