# Multi-modal assessment of GABA function in psychosis

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $652,529

## Abstract

Abstract
Considerable evidence implicates GABAergic dysfunction in the psychosis spectrum, which includes
schizophrenia and bipolar disorder. GABAergic agents treat psychosis spectrum patients, often for anxiety,
and the response of catatonic patients to GABA-enhancing benzodiazepines suggests a deeper link between
GABA and psychosis. Post-mortem work strongly implicates GABAergic interneurons in these patients, but
the links between these findings, clinical phenotype and therapeutics are far from clear. Accordingly, this
proposal will undertake a transdiagnostic approach to elaborate linkages between GABA and the
negative affective states (NA, e.g. anxiety, stress sensitivity) that are common across this psychosis
spectrum. Using a multimodal neuroimaging strategy, magnetic resonance spectroscopy (MRS) with be
combined with a pharmaco-fMRI (phfMRI) challenge paradigm measuring blood oxygenation level dependent
(BOLD) changes. MRS studies of GABA levels in the psychosis spectrum have yielded inconsistent findings,
which this proposal will address by positing two processes: 1) Elevated GABA in early psychosis patients in
the rostral medial frontal cortex (rMFC), and 2) Reduced GABA associated with more NA. The investigators
will pursue preliminary data showing that NA may be linked to low GABA levels in the rMFC, and when
controlling for NA, early psychosis patients have higher GABA in the rMFC. In Aim 1, this study will utilize
GABA MRS to assess GABA levels in psychosis spectrum patients, comparing early episode patients (50%
not taking antipsychotics) with healthy controls, as well as schizophrenia, schizoaffective and bipolar patients.
By probing three distinct voxels in the medial frontal cortex, the investigators will show specific regional
effects in the rMFC and demonstrate that antipsychotic medication is associated with reduced GABA levels.
In Aim 2, the phfMRI challenge paradigm with a benzodiazepine will be used to measure dynamic GABA
function. In published work, the investigators have demonstrated abnormal BOLD response (increased rather
than decreased signal) in schizophrenia in the dorsomedial prefrontal cortex (dmPFC). This BOLD response
to a GABAergic manipulation is correlated with NA in both patients and controls, consistent with a
transdiagnostic dimension. The project will extend these findings across the psychosis spectrum. As the
regulation of GABA function plays a critical role in the excitatory/inhibitory (E/I) balance, the phfMRI probe
serves as a proxy measure of E/I balance, and it will be used to test the hypothesis that this dynamic
measure is associated with NA and GABA concentration measured with MRS. Expected Impact: Successful
achievement of study aims will clarify GABAergic dysfunction in the psychosis spectrum, leading to follow-up
studies on the role of illness stage in GABA activity and the E/I balance. As NA is a strong, transdiagnostic
predictor of functional outcome, the impact of this work will establish ...

## Key facts

- **NIH application ID:** 10196982
- **Project number:** 5R01MH118634-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Stephan F Taylor
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $652,529
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10196982

## Citation

> US National Institutes of Health, RePORTER application 10196982, Multi-modal assessment of GABA function in psychosis (5R01MH118634-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10196982. Licensed CC0.

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