# Towards an Integrated Understanding of Neurotransmitter Dysfunction in Schizophrenia: a Multimodal MRI Study

> **NIH NIH K23** · STATE UNIVERSITY NEW YORK STONY BROOK · 2024 · $66,993

## Abstract

PROJECT SUMMARY / ABSTRACT
 Schizophrenia is among the most severe and burdensome medical conditions worldwide, yet the brain alterations
that lead to the symptoms of schizophrenia remain unknown. This K23 application presents a research and training
program that will support the applicant on a path towards becoming an NIH-funded independent investigator focused
on understanding the neurobiology of schizophrenia and related psychotic disorders. The activities in this application
build on the candidate’s prior training and are set in a resource-rich environment that will foster her development of
expertise in 1) application of MRS and advanced MRI neuroimaging methodologies; 2) physician-scientist approaches to
studying pathophysiology in patients with schizophrenia; 3) neurocircuitry and systems neuroscience perspectives on
hippocampus pathology in psychotic disorders; and 4) responsible conduct of research. The overarching goal of the
research to be carried out in this application is to take findings from animal models of schizophrenia, which were
motivated by original research in patients with the disorder, back to the clinical setting in order to determine whether
the brain circuit alterations observed in the animal models are observable in human patients. Specifically, findings in the
prenatal methylazoxymethanol acetate (MAM) rodent model, which was developed to model the alterations in
dopamine function seen in patients with schizophrenia, suggest hyperactivity of the ventral (anterior) hippocampus may
increase its glutamatergic output to the ventral striatum and lead, via ventral pallidal and other GABAergic projections to
the ventral midbrain, to disinhibited firing of dopamine neurons. In addition, a convergence of several post mortem and
in vivo imaging findings in patients suggests that abnormal GABAergic activity in the hippocampus may further
compound hippocampal glutamatergic overdrive. This project will directly test the relationships among these
neurochemical alterations in individual medication-free patients with schizophrenia using sophisticated magnetic
resonance imaging methods. If this non-invasive, multimodal imaging paradigm provides evidence to relate hippocampal
GABA and glutamate abnormalities to dopamine system dysfunction in patients with schizophrenia, it would have
important implications for the understanding of the brain bases of schizophrenia, and would generate a novel
multimodal imaging paradigm for testing new molecular, anatomical, and circuit-modulating targets for treatment of
this devastating illness.

## Key facts

- **NIH application ID:** 10924604
- **Project number:** 3K23MH115291-05S1
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Jodi Jay Weinstein
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $66,993
- **Award type:** 3
- **Project period:** 2018-07-09 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10924604

## Citation

> US National Institutes of Health, RePORTER application 10924604, Towards an Integrated Understanding of Neurotransmitter Dysfunction in Schizophrenia: a Multimodal MRI Study (3K23MH115291-05S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10924604. Licensed CC0.

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