# Neuromarkers of Treatment for Comorbid Posttraumatic Stress Disorder and Alcohol Use Disorder

> **NIH VA I01** · VA SAN DIEGO HEALTHCARE SYSTEM · 2022 · —

## Abstract

Veterans with posttraumatic stress disorder (PTSD) often have serious problems with alcohol, and many
continue to suffer following our best treatments. While Prolonged Exposure (PE) is a first-line treatment,
targeted adjunctive pharmacotherapy may benefit those with both an alcohol use disorder and PTSD
(AUD/PTSD). In fact, recent evidence suggests that topiramate (TOP) may be uniquely effective for comorbid
AUD/PTSD patients. TOP may improve treatment for the comorbidity of AUD and PTSD by counteracting
neuroadaptive processes that occur as part of each disorder. However, despite exciting new evidence that
TOP may enhance psychotherapeutic treatment for AUD/PTSD, no work has been done to understand how
TOP may affect AUD/PTSD relevant neurocircuits. Given the promising combination of PE and TOP, a recently
funded randomized controlled trial (RCT) will examine their combined effectiveness in the treatment of
Veterans with AUD/PTSD. To identify the mechanisms of action of this novel combination of treatments, and
the specific contribution of TOP to this dynamic, we propose to use functional magnetic resonance imaging
(fMRI), in the context of this RCT, to examine clinically relevant neural markers of AUD/PTSD that predict
course and define remission.
 Participants will be 88 Veterans with AUD and PTSD who will receive one of two 16-week long treatment
conditions as part of an already funded RCT comparing the relative effectiveness of PE plus placebo
(PE+PLA), against PE plus TOP (PE+TOP). Our central hypothesis is that PE will improve neuromodulatory
function of the prefrontal cortex over emotional reactivity centers, and that the addition of TOP will enhance
PE’s effects on threat- and craving-related activation during pictorial reactivity paradigms. Our primary aims are
(1) to determine whether baseline patterns of brain response in networks subserving fear processing or alcohol
cue reactivity predict AUD/PTSD response across treatments, and (2) to compare the effect of each treatment
on the neural subprocesses thought to maintain AUD and PTSD.
 The proposed translational neuroimaging study has the potential to elucidate the processes by which
evidence based treatments may improve functional and psychological recovery for a highly prevalent and
highly impaired population of Veterans. Linking clinically relevant neural patterns to psychotherapeutic gains
can improve our ability to effectively triage and treat Veterans with this crippling comorbidity. Therefore, the
fundamental rationale for this study is to improve the evidence base that informs how patients with AUD and
PTSD can attain sustained recovery from both of these disorders.
 The effects of TOP have not been evaluated using fMRI in an AUD, PTSD, or AUD/PTSD sample, let alone
Veterans. This application seeks to elucidate the mechanisms through which treatments may drive recovery,
and for whom recovery is most likely, via the integration of state-of-art-neuroimaging and evidence based
tr...

## Key facts

- **NIH application ID:** 10295166
- **Project number:** 5I01CX001762-04
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** ANDREA SPADONI TOWNSEND
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-10-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10295166

## Citation

> US National Institutes of Health, RePORTER application 10295166, Neuromarkers of Treatment for Comorbid Posttraumatic Stress Disorder and Alcohol Use Disorder (5I01CX001762-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10295166. Licensed CC0.

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