# A Multidimensional Dissection of Antipsychotic Treatment Response in Early Schizophrenia

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $682,399

## Abstract

PROJECT SUMMARY
Schizophrenia spectrum disorders, among the most disabling of all psychiatric conditions, place a significant
burden on the individuals who experience them, as well as their family members and society. Up to 35% of
individuals with the disorders do not demonstrate an adequate response to antipsychotic treatment, and remain
refractory to first-line therapies, which contributes to the burden and morbidity of the illness, often leaving patients
unable to integrate with their communities. A limited understanding of the neurobiological mechanism underlying
successful or unsuccessful antipsychotic treatment continues to hinder novel therapeutic development and
optimization of our existing therapies for these disorders. While recent work has demonstrated the utility of
functional and spectroscopic MR to elucidate the mechanisms underlying antipsychotic treatment, a more
comprehensive understanding of molecular and neuronal changes associated with treatment efficacy is lacking.
In this study, we address this knowledge gap by utilizing a multidimensional strategy with high-field, 7-Tesla
neuroimaging to deconstruct the mechanism underlying antipsychotic response in a cohort of individuals with
early schizophrenia. This project focuses on the cortical-basal ganglia system with several innovative
approaches, including assays of (1) the dopamine system via neuromelanin-sensitive MRI; (2) magnetic
resonance spectroscopic imaging of cortical γ-aminobutyric acid and glutamate functioning; and (3) both
hypothesis and data-driven multivariate approaches to cortico-basal ganglia functional connectivity. Acutely
psychotic patients with early schizophrenia spectrum illness will be examined in this naturalistic and prospective
study. They will undergo scanning during treatment initiation, clinical assessments at 2-week intervals, and will
be rescanned after 8 weeks of treatment. A group of healthy controls will also be examined to establish normal
ranges of our neuroimaging measures. Results of this work will provide a more comprehensive foundation for
our understanding of antipsychotic treatment-related neurobiology, which will facilitate biomarker development,
mechanistic clinical trials, and the development of next-generation therapeutic strategies.

## Key facts

- **NIH application ID:** 10296198
- **Project number:** 1R01MH124705-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Deepak K Sarpal
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $682,399
- **Award type:** 1
- **Project period:** 2021-06-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10296198

## Citation

> US National Institutes of Health, RePORTER application 10296198, A Multidimensional Dissection of Antipsychotic Treatment Response in Early Schizophrenia (1R01MH124705-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10296198. Licensed CC0.

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