# Impaired dynamic neurobiological responses in alcoholism and early trauma to predict relapse after treatment

> **NIH NIH R01** · YALE UNIVERSITY · 2023 · $620,658

## Abstract

Project Summary/Abstract
Early trauma (ET) is a significant obstacle to alcohol recovery. Patients with alcohol use disorder
(AUD) who experienced early trauma are at a higher risk of frequent and early relapse and suffer from
severe clinical symptoms including emotion and stress-related difficulties. However, neural
mechanisms linking alcoholism, early trauma and high relapse risk remain unclear. Two biological
systems, stress-related brain circuits and the hypothalamic–pituitary–adrenal (HPA) axis system, are
implicated in the pathologies of both AUD and ET. Concurrent examination of these two systems using
multimodal neuroimaging techniques (e.g., simultaneous brain and stress hormone monitoring) may
clarify the relationship between AUD and ET. Using this novel approach, our prior study showed that a
lack of dynamic increase in the ventromedial prefrontal cortex (VmPFC) during stress was a critical
predictor of ineffective coping, disrupted HPA axis response to stress, and increased alcohol
consumption. Preliminary results also indicated that impaired dynamic VmPFC recovery during stress
was associated with comorbid AUD/ET and early relapse. This pattern of findings leads us to
hypothesize that impaired dynamic VmPFC response to stress may be a novel marker of comorbid
alcoholism and early trauma, which underlies high relapse risk. Using functional magnetic resonance
imaging (fMRI) combined with a prospective clinical outcome design, the proposed study aims to utilize
brain-HPA axis markers of co-occurring alcoholism and early trauma and to examine whether these
markers contribute to early relapse after treatment. We propose a 5-year study with four
demographically-matched groups (total N=160; N=40 each; equal sex ratio); these groups will include
AUD patients with and without ET and moderate drinkers with and without ET. Participants will
complete an fMRI session while viewing a series of stress, alcohol, and neutral cues. After the
multimodal scan, AUD patients will be engaged in eight weeks of standard, empirically-validated
outpatient treatment and then prospectively followed for 90 days. To accurately capture relapse rate,
we will conduct face-to-face follow-up interviews at 14, 30, and 90 days after treatment in conjunction
with daily monitoring of stress and alcohol related behaviors using a smartphone app. Successful
completion of the proposed aims has the potential to identify the neural mechanisms underlying
comorbid alcoholism and early trauma and associated relapse risk, which may be further explored to
develop new treatment targets and to improve clinical outcomes in AUD patients with early trauma.

## Key facts

- **NIH application ID:** 10565677
- **Project number:** 5R01AA026844-05
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** DONGJU SEO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $620,658
- **Award type:** 5
- **Project period:** 2019-05-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10565677

## Citation

> US National Institutes of Health, RePORTER application 10565677, Impaired dynamic neurobiological responses in alcoholism and early trauma to predict relapse after treatment (5R01AA026844-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10565677. Licensed CC0.

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