# Contribution of Glutamate Excess and Inflammation to Progressive White Matter Changes in Psychosis

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2021 · $636,324

## Abstract

Schizophrenia is a complex disorder associated with subtle white matter abnormalities that progress
over time. Alterations are associated with disease severity across symptom dimensions and worse overall
outcomes, but no strategies exist to attenuate white matter disease progression. This is largely because the
underlying pathophysiological processes remain unknown. Glutamate excess and inflammation may be
contributing factors, but we do not know if there is a period early in the illness where these affect white matter
or if they alter white matter across illness stages.
 We propose to use multimodal neuroimaging to study 60 unmedicated first-episode psychosis patients,
60 unmedicated chronic psychosis patients, and 120 matched healthy controls. We will use (1) advanced
diffusion weighted imaging to measure white matter structural integrity, (2) Magnetic Resonance Spectroscopy
to measure glutamatergic and inflammatory markers in white matter, and (3) blood samples to measure
peripheral inflammatory and glutamatergic markers to test the hypothesis that white matter integrity deficits
increase as a function of illness stage and that glutamate excess and inflammation contribute to white matter
pathology.
 Identification of factors that contribute to progressive white matter deficits holds the promise to
transform our mechanistic understanding and inform biomarkers for targeted drug development investigating
the potential of glutamatergic or anti-inflammatory agents delaying or attenuating white matter decline in
schizophrenia.

## Key facts

- **NIH application ID:** 10200644
- **Project number:** 5R01MH118484-03
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Nina Vanessa Kraguljac
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $636,324
- **Award type:** 5
- **Project period:** 2019-08-26 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200644

## Citation

> US National Institutes of Health, RePORTER application 10200644, Contribution of Glutamate Excess and Inflammation to Progressive White Matter Changes in Psychosis (5R01MH118484-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10200644. Licensed CC0.

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