Neurobiological Responses in Alcoholism and Early Trauma

Alcohol use disorder (AUD) accompanied by early trauma presents clinical challenges, including elevated rates of comorbid emotional symptoms and relapse. To better understand this co-occurring condition, this study investigates the neurobiological responses associated with AUD and early trauma. Using a multimodal neuroimaging approach, including functional magnetic resonance imaging (fMRI), the study concurrently measures brain activity and stress hormone responses in individuals with AUD and control participants, both with and without early trauma. The primary goal is to examine neurobiological responses and relapse patterns following treatment in individuals with AUD, with and without a history of early trauma. Conventional alcohol treatments often fail to specifically address the emotional complications in AUD individuals with early trauma. Therefore, this study also explores whether incorporating stress regulation into alcohol relapse prevention can improve outcomes for this population. Following baseline assessments that included multimodal neuroimaging, all participants with AUD received an 8-week outpatient treatment program integrating cognitive-behavioral methods focused on emotion regulation with stress reduction techniques, particularly self-regulated breathing strategies.

Study Overview

• Status: Completed
• Conditions: Alcohol Use Disorder; Early Trauma Complications
• Intervention / Treatment: Behavioral: 8-week outpatient treatment

Detailed Description

The study recruited four demographically matched groups (age, sex ratio): individuals with AUD with and without a history of early trauma, and moderate drinkers with and without early trauma. Study procedures involved functional magnetic resonance imaging (fMRI), an eight-week outpatient treatment program, and a 90-day follow-up period. During fMRI sessions, participants engaged in a validated emotion provocation task, viewing stress, alcohol-cue, and neutral images while concurrent brain and stress hormone data are collected. Individuals with AUD completed baseline assessments, including multimodal neuroimaging, and then participated in an 8-week treatment program consisting of two sessions per week. This program integrated cognitive-behavioral techniques focused on emotion regulation with breathing-based stress management. Control participants completed baseline assessments including multimodal neuroimaging but did not receive any treatment. Following the treatment, participants with AUD were prospectively followed for 90 days, with remote follow-up interviews conducted at 14, 30, 90 days via video communication.

• Study Type: Interventional
• Enrollment (Actual): 148
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06492
      • Yale University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

AUD inclusion Criteria:

• Alcohol use disorder
• Either low or high early trauma (based on the Childhood Trauma Questionnaire)
• Body mass index (BMI) up to 35 (due to weight limitations of the MRI scanner)

AUD exclusion Criteria:

• Current or past substance use disorder other than alcohol; excluding caffeine and nicotine
• Psychiatric disorders except for mood and anxiety disorders
• Any significant current medical conditions
• Women who are peri- and post- menopausal, pregnant or lactating
• MRI specific exclusion criteria (e.g., claustrophobia, implanted metal in the body)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Alcohol use disorder with early trauma; Individuals with alcohol use disorder participated in an equivalent 8-week outpatient treatment program.	Behavioral: 8-week outpatient treatment; Individuals with AUD participated in an 8-week treatment program integrating cognitive behavioral techniques focused on emotion regulation with breathing-based stress management.
Other: Alcohol use disorder without early trauma; Individuals with alcohol use disorder participated in an equivalent 8-week outpatient treatment program.	Behavioral: 8-week outpatient treatment; Individuals with AUD participated in an 8-week treatment program integrating cognitive behavioral techniques focused on emotion regulation with breathing-based stress management.
No Intervention: Controls with early trauma; Control participants did not receive any treatment.
No Intervention: Controls without early trauma; Control participants did not receive any treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain Response	Brain responses during the viewing of stress, alcohol-cue, and neutral images were examined using functional magnetic resonance imaging (fMRI) during an emotion provocation task. A regions of interest (ROI) analysis was conducted to assess brain activity in the right ventromedial prefrontal cortex (VmPFC, BA10), a region identified a priori. The VmPFC ROI was defined using the Yale-Brodmann atlas, and beta values were obtained using the BioImage Suite. The beta coefficient represents the extent to which a specific condition contributes to changes in the BOLD (Blood Oxygen Level Dependent) signal in a particular brain region. A positive beta in the vmPFC would indicate an increased vmPFC response, whereas a negative beta would indicate a decreased vmPFC response compared to baseline. The magnitude of the beta reflects the strength of this effect: a larger absolute value, (whether positive or negative), suggests a greater change in brain activation in response to the condition.	baseline
Stress Hormone Response (Cortisol to ACTH Ratio)	Cortisol to Adrenocorticotropic Hormone (ACTH) ratio indicates the relationship between cortisol secretion and ACTH stimulation at baseline. Cortisol is measured in micrograms per deciliter (µg/dL) and ACTH (adrenocorticotropic hormone) is measured in picograms per milliliter (pg/mL). Therefore, the unit of cortisol to ACTH ratio is expressed in µg/dL per pg/mL. Stress hormone samples were collected during the MRI scan.	baseline
Time to Relapse	The first day of alcohol consumption after treatment during the 90-day follow-up period. Alcohol use data was measured using the Timeline Follow-Back (TLFB) method, a calendar-based self-report tool to track alcohol use. Participants recalled their drinking behavior using a calendar and reported both the days they consumed alcohol and the number of drinks consumed on each of those days. Alcohol use data during the 90-day follow-up period is available only for the AUD/ET and AUD/NT groups, as the MD/ET and MD/NT groups had not initiated treatment.	up to 90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amount of Alcohol Consumption (Weekly)	Average weekly alcohol consumption over the 90-day follow-up period. Alcohol use data was measured using the Timeline Follow-Back (TLFB) method, a calendar-based self-report tool to track alcohol use. Participants recalled their drinking behavior using a calendar and reported both the days they consumed alcohol and the number of drinks consumed on each of those days. Alcohol use data during the 90-day follow-up period is available only for the AUD/ET and AUD/NT groups, as the MD/ET and MD/NT groups had not initiated treatment.	up to 90 days
Frequency of Alcohol Use (Percentage)	Percentage of alcohol use days over the 90-day follow-up period. Alcohol use data was measured using the Timeline Follow-Back (TLFB) method, a calendar-based self-report tool to track alcohol use. Participants recalled their drinking behavior using a calendar and reported both the days they consumed alcohol and the number of drinks consumed on each of those days. Alcohol use data during the 90-day follow-up period is available only for the AUD/ET and AUD/NT groups, as the MD/ET and MD/NT groups had not initiated treatment.	up to 90 days

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: Dongju Seo, PhD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2019
• Primary Completion (Actual): September 8, 2023
• Study Completion (Actual): September 8, 2023

Study Registration Dates

• First Submitted: October 14, 2019
• First Submitted That Met QC Criteria: October 14, 2019
• First Posted (Actual): October 16, 2019

Study Record Updates

• Last Update Posted (Estimated): November 14, 2024
• Last Update Submitted That Met QC Criteria: October 23, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: fMRI; Alcohol use disorder; Alcohol relapse; Early trauma; Stress hormone
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Drinking Behavior; Alcohol-Related Disorders; Alcoholism; Alcohol Drinking; Wounds and Injuries
• Other Study ID Numbers: 2000024809; 1R01AA026844 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No