# Imaging Framework for Testing GABAergic Drugs in Bipolar Alcoholics

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2022 · $148,995

## Abstract

Project Summary / Abstract
 Bipolar disorder (BD) is the Axis I psychiatric condition most strongly associated with alcohol use disorder
(AUD). Individuals with co-occurring AUD and BD (AUD+BD) have substantially worse clinical outcomes than
those with either BD or AUD alone. Nonetheless, little is known about optimal treatment for individuals with
AUD+BD. A novel approach to selecting, and ideally developing, medications for AUD+BD treatment trials would
be to target neurochemical dysfunctions characteristic of individuals with both AUD and BD. Our lab has
demonstrated unique disturbances in prefrontal gamma-Aminobutyric acid (GABA) and glutamate
concentrations in this population using proton magnetic resonance spectroscopy (1H-MRS), with AUD+BD
individuals having significantly lower levels of GABA and glutamate, which were associated with elevated craving
and impulsivity, relative to individuals with BD alone, AUD alone, or healthy controls. Our ongoing double-blind,
randomized, crossover study is evaluating: a) whether medications that have been demonstrated to normalize
cortical GABA (i.e., gabapentin) and glutamate (i.e., N-Acetylcysteine [NAC]) levels in other diseases, may
similarly act to normalize prefrontal GABA and glutamate levels in AUD+BD, and b) whether normalization of
these levels will be associated with improvements in functional brain activity to response inhibition and alcohol
cue-reactivity tasks, as well as drinking and mood symptoms. Positive results may support investigation of
gabapentin and/or NAC as adjunctive treatments for AUD+BD in large-scale clinical trials, as well as provide
successful demonstration of a multimodal neuroimaging platform for evaluating the promise of GABAergic and
glutamatergic drugs for AUD and/or BD. Unfortunately, following a 3-year period of success, with roughly 80%
of year-end enrollment targets met and participant-retention expectations exceeded, our study was brought to a
screeching halt by the COVID-19 pandemic. The pandemic has severely impeded the progress of the study over
the past 2 years, threatening both the validity of our results as well as the viability of New/Early-Stage Investigator
Dr. Prisciandaro's research career in treatment development for individuals with BD+AUD. As a result, Dr.
Prisciandaro (PI), in consultation with his Program Officer, is requesting a 1-year Administrative Supplement
(i.e., “Extension with Funds”) in order to mitigate the substantial damage that the pandemic will otherwise inflict
on our study and his career by allowing him to extend participant enrollment for one additional year. If funded,
this Supplement will restore the statistical power and validity of our study, thereby facilitating successful
competitive continuation (renewal) of Dr. Prisciandaro's first R01 grant.

## Key facts

- **NIH application ID:** 10544656
- **Project number:** 3R01AA025365-05S1
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** James Joseph Prisciandaro
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $148,995
- **Award type:** 3
- **Project period:** 2017-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10544656

## Citation

> US National Institutes of Health, RePORTER application 10544656, Imaging Framework for Testing GABAergic Drugs in Bipolar Alcoholics (3R01AA025365-05S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10544656. Licensed CC0.

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