# Next Generation Diffusion MRI Biomarkers for Prodromal Schizophrenia

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $443,750

## Abstract

Project Summary/Abstract
Schizophrenia is a devastating and debilitating disorder that affects about 1% of the population and is
characterized by a range of symptoms including delusions, hallucinations, impaired cognitive function, mood
disturbances and social withdrawal. Little is known about the neuropathology of schizophrenia, yet imaging
studies of its earliest stages have the potential to identify initial pathologic traces preceding psychosis onset.
New research approaches now allow clinicians to investigate prodromal schizophrenia subjects (prodromes)
who experience attenuated psychotic symptoms, and are at high-risk for developing schizophrenia. Diffusion
MRI is a promising imaging technique for prodromes, since it consistently and reliably identifies abnormalities
in all stages of schizophrenia. However, current diffusion MRI biomarkers and analysis methods have limited
sensitivity and poor specificity to the underlying microstructural pathology, which pose barriers to further
understanding the etiology of schizophrenia, and to new developments in pharmacological treatment.
The goal of this proposal is to develop tools and apply next generation diffusion MRI biomarkers, such as free-
water imaging, neurite density, neurite orientation dispersion, and Kurtosis. These biomarkers improve
specificity and sensitivity of currently available measures, and are more suited to identify subtle pathologies.
Our previous research suggests that neurodevelopmental, neuroinflammatory and neurodegenerative
microstructural pathologies are involved in schizophrenia. We hypothesize that neuroinflammation is the
dominant pathology responsible for triggering attenuated psychotic symptoms, and that abnormal
neurodevelopment, which changes how the brain appears or grows, may be a predisposition for psychosis.
Using next generation diffusion MRI biomarkers can distinguish between these micropathologies, which will
help explaining their association with attenuated psychotic symptoms, and reveal their role in psychosis onset.
Large-scale studies, such as the North American Prodrome Longitudinal Study (NAPLS), have already
collected large datasets of CHR that include dMRI data, and this data will be available to us. Our approach is
to leverage from these existing data and utilize it to study the pathological correlates of prodromal symptoms,
unlike previous studies that focused on risk for conversion to SZ. The assembled unprecedentedly large data
(n>700) provide ample sensitivity to identify subtle prodromal pathologies.
A highly trained team of computer scientists and clinical neuroscience researchers will work to develop novel
tools for next generation diffusion MRI biomarkers in order to localize and to characterize the neurobiology that
underlies prodromal symptomatology. The results of this study will have an important impact on our
understanding of biological mechanisms underlying the initial stages of schizophrenia, and will lead to
improved diagnosis and po...

## Key facts

- **NIH application ID:** 9974564
- **Project number:** 5R01MH108574-05
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Ofer Pasternak
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $443,750
- **Award type:** 5
- **Project period:** 2016-08-10 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974564

## Citation

> US National Institutes of Health, RePORTER application 9974564, Next Generation Diffusion MRI Biomarkers for Prodromal Schizophrenia (5R01MH108574-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9974564. Licensed CC0.

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