# Leveraging biomarkers for personalized treatment of alcohol use disorder comorbid with PTSD

> **NIH NIH P01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $1,202,772

## Abstract

Overall Summary
The overarching goal of the proposed center is to leverage molecular and circuit biomarkers to advance the
understanding of mechanisms and personalized treatment of topiramate treatment of Alcohol Use Disorder
comorbid with PTSD. We propose an integrative translational focus on alterations in excitatory and inhibitory
signaling, focusing on GABA and glutamate and related circuitry, to model the neurobiology of PTSD comorbid
with PTSD and the mitigating effects of topiramate. We will characterize excitatory and inhibitory molecular
markers in an animal model of AUD comorbid with PTSD, utilizing genomic markers in the brain and plasma
markers in rodents. In clinical trial participants we will characterize excitatory and inhibitory neuronal signaling
by ascertaining plasma markers, GRIK 1 genotype and neural circuit markers utilizing TMS evoked potentials
in EEG, task-based functional MRI and MR spectroscopy.
This goal will be achieved through the activities of three research projects supported by two research cores,
the administrative core and the Scientific Advisory Board (Figure1). In Project 1 lead by Silvia Fossati Ph.D.
and Jorge Manzanares Robles Ph.D. we will study the behavioral and molecular effects of two doses of
topiramate vs. vehicle in animal models of AUD alone, PTSD alone and AUD+PTSD. In Project 2 lead by
Michael Bogenschutz M.D. and Joshua Lee M.D. we will study the behavioral, genetic and plasma biomarker
effects of topiramate vs. placebo in 150 participants with co-occurring AUD and PTSD. In project 3 lead by
Amit Etkin M.D., Ph.D. and Charles R. Marmar M.D. we will ascertain multi-modal imaging markers including
task based fMRI, TMS evoked potentials in EEG and MRS. Imaging markers will be used to characterize
excitatory and inhibitory circuits in Project 2 clinical trial participants with AUD+PTSD to determine predictors
and mechanisms of topiramate vs. placebo treatment outcomes. Plasma biomarkers in Project 2 will be
related to the same or homologous plasma biomarkers in Project 1. Circuit markers from Project 3 will be
related to genomic markers in the same or homologous brain regions in Project 1. The Biofluids Biomarker
Core (BBC) lead by Dr. Fossati will support collection of plasma biomarkers (GABA, glutamate, HPA axis,
neuropeptides, neuroinflammatory and oxidative stress) in animals in Project 1 and clinical trial participants in
Project 2. The Analytics and Biostatistics Core (ABC) lead by Eugene Laska Ph.D. and Carole Segal Ph.D.
will support experimental design, formulation of hypothesis, power calculations, and data integrity,
management and analysis for Project 1, 2 and 3, implementing advanced statistical models for individualized
prediction of response to topiramate in Project 1 and Project 2.

## Key facts

- **NIH application ID:** 10237280
- **Project number:** 5P01AA027057-04
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Charles R Marmar
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,202,772
- **Award type:** 5
- **Project period:** 2018-09-20 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10237280

## Citation

> US National Institutes of Health, RePORTER application 10237280, Leveraging biomarkers for personalized treatment of alcohol use disorder comorbid with PTSD (5P01AA027057-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10237280. Licensed CC0.

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