# Biomarkers of Conversion Risk and Treatment Response in Early-Stage Schizophrenia

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $696,494

## Abstract

ABSTRACT
Schizophrenia (SZ) is a highly debilitating neuropsychiatric disorder of young adulthood onset and a
leading cause of disability worldwide. While treatments delivered at early stages of the disorder may be
effective at reducing psychosis or altering the course of the disease, there are currently no biomarkers
capable of identifying subjects at ultra-high risk (UHR) for psychosis who are likely to convert to the full
clinical syndrome; or those in early stages of SZ who are likely to respond to treatment and would be
good candidates for available proactive, symptomatic or future disease-modifying treatments; or those
who would not respond and can be spared unnecessary medication exposure. The lack of these vitally
important biomarkers provides a compelling rationale for the present multidisciplinary, transnational
research project, which aims to develop and validate highly promising noninvasive and objective proton
magnetic resonance spectroscopy (1H MRS)-based biomarkers for assessing conversion risk in UHR
subjects and monitoring treatment response in first-episode psychosis (FEP) patients. In support of the
viability of this overall objective is a large body of data, reported by the applicants and others, that show
(a) that levels of glutamate (Glu) and -aminobutyric acid (GABA) – respectively, the major excitatory and
inhibitory amino acid neurotransmitter systems - are abnormally elevated in medication-naïve and
unmedicated UHR, FEP and chronic SZ cohorts; (b) that the effect of treatment with antipsychotic
medications may be to lower or normalize brain levels of both Glu and GABA; and (c) that Glu elevations
at baseline in UHR subjects may be a reliable predictor of conversion to full psychosis. To investigate the
potential of these in vivo brain Glu and GABA abnormalities to serve as biomarkers of conversion risk in
UHR subjects and of treatment response in early-stage SZ, the applicants propose to use 1H MRS to
measure Glu and GABA levels in the largest cohorts of medication-naïve UHR and FEP subjects to date,
at baseline and at conversion or at 2 years in UHR subjects; and at baseline and following 4 weeks of
antipsychotic treatment in FEP subjects. The hypotheses to be tested are that (1) baseline elevations of
Glu and GABA in UHR subjects will predict the risk of conversion to full psychosis; that (2) both GABA
and Glu will be elevated at baseline in FEP subjects and decrease or normalize with second-generation
antipsychotic treatment; and that (3) levels of both GABA and Glu will correlate positively with clinical
measures in both groups at baseline and or negatively or not with treatment response in FEP subjects.
If successful, the proposed studies have the potential to establish 1H MRS measures of brain GABA and
Glu as predictors of conversion risk and biomarkers of treatment response or non-response, support the
exploration of novel glutamate- or GABA-based treatments that may be more effective and present lower
risks, and...

## Key facts

- **NIH application ID:** 9954166
- **Project number:** 5R01MH110270-04
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Ragy Ramsis Girgis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $696,494
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9954166

## Citation

> US National Institutes of Health, RePORTER application 9954166, Biomarkers of Conversion Risk and Treatment Response in Early-Stage Schizophrenia (5R01MH110270-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9954166. Licensed CC0.

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