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

> **NIH NIH P01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $85,933

## Abstract

Summary
The Blood Biomarkers Core (BBC) is led by Dr. Silvia Fossati. For Project 1, blood and brain samples from all
mice will be collected at sacrifice to quantify: 1) molecular biomarkers in animals subjected to all alcohol and/or
PTSD-like models after treatment with two doses of topiramate (TPM) or vehicle to clarify the mechanisms of
TPM action, and 2) biomarkers for the neurobiological comparison of animal models of alcohol+PTSD with
PTSD-like animal models alone, alcohol models alone, naïve control animals, and resilient animals. For Project
2, blood will be collected from all enrolled randomized clinical trial (RCT) participants at 2 time points (before
randomization and at week 12), and processed to determine molecular biomarkers, predictors of therapeutic
efficacy and GRIK1 genotype, following best practices for blood biomarker analysis developed by our group at
the NYU Cohen Veterans Center. Using Simoa and ELISA assays, we will determine the blood
concentration of the following molecules: 1) excitatory and inhibitory amino acids altered in AUD, PTSD
and PTSD+AUD and central to the hypothesized mechanisms of action of TPM (gluatamate and GABA); 2)
peptides and hormones regulating responses of the hypothalamic–pituitary–adrenal (HPA) axis (corticotrophin
releasing factor (CRF), corticosterone/cortisol, neuropeptide Y, and brain-derived neurotrophic factor (BDNF));
3) biomarkers implicated in neuroinflammation (IL6, IL10, IL1α, TNFα, and glial fibrillary acidic protein); and 4)
apoptosis, oxidative stress and mitochondrial dysfunction markers (cytochrome C). Integration across projects
will be achieved by two design elements and three analytic strategies. Integrative Design Elements include:
1) mice subjected to alcohol and/or PTSD-like models in Project 1 will be stratified and randomized to
topiramate/vehicle and PTSD+AUD clinical trial participants in Project 2 will be stratified and randomized to
topiramate/placebo, creating parallel designs to advance discovery of mechanisms of topiramate action and
predictors of treatment response; and 2) all blood biomarkers in mice in Project 1 will be ascertained in clinical
trial participants for Project 2 (cortisol will replace corticosterone). Integrative Analytic Strategies include: 1)
blood biomarkers levels after topiramate/placebo treatment in Project 2 will be related to plasma biomarkers
levels in alcohol+PTSD models after topiramate/vehicle treatment in Project 1; 2) blood biomarker values
obtained in clinical trial participants in Project 2 will be related to their Project 2 clinical data and to fMRI,
TMS/EEG and MRS markers derived from Project 3; and 3) gene expression and protein expression markers
ascertained in PFC, amygdala, cingulate, insula, VTA and accumbens in mice in Project 1 will be related to
circuit markers obtained in the same brain regions in clinical trial participants in Project 3. Further, because we
will be able to collect a higher blood volume in humans than mic...

## Key facts

- **NIH application ID:** 9996330
- **Project number:** 5P01AA027057-03
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Silvia Fossati
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $85,933
- **Award type:** 5
- **Project period:** 2018-09-20 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9996330

## Citation

> US National Institutes of Health, RePORTER application 9996330, Leveraging biomarkers for personalized treatment of alcohol use disorder comorbid with PTSD (5P01AA027057-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9996330. Licensed CC0.

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