Alcohol Use Disorder, Early Trauma Complications
Conditions
Keywords
Alcohol use disorder, Early trauma, fMRI, Stress hormone, Alcohol relapse
Brief summary
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.
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.
Interventions
Individuals with AUD participated in an 8-week treatment program integrating cognitive behavioral techniques focused on emotion regulation with breathing-based stress management.
Sponsors
Study design
Intervention model description
Following baseline assessments including multimodal neuroimaging, AUD individuals with and without a history of early trauma received an equivalent 8-week outpatient treatment. Control participants with and without early trauma did not receive any treatment after baseline assessments.
Eligibility
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brain Response | baseline | 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. |
| Stress Hormone Response (Cortisol to ACTH Ratio) | baseline | 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. |
| Time to Relapse | up to 90 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Amount of Alcohol Consumption (Weekly) | up to 90 days | 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. |
| Frequency of Alcohol Use (Percentage) | up to 90 days | 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. |
Countries
United States
Participant flow
Recruitment details
All participants were recruited starting on October 3, 2019 through online platforms and flyers. A recruitment center was located in New Haven, Connecticut.
Pre-assignment details
Out of the 148 enrolled participants, 17 individuals did not start the study due to participant withdrawal (N=14), MRI-day ineligibility (N=2), and non-compliance (N=1).
Participants by arm
| Arm | Count |
|---|---|
| AUD/ET Individuals with alcohol use disorder (AUD) and early trauma (ET):
Individuals with alcohol use disorder completed baseline assessments and then received an 8-week outpatient treatment that integrates alcohol treatment based on cognitive behavioral methods with breathing-based stress management. | 34 |
| AUD/NT Individuals with alcohol use disorder without early trauma:
Individuals with alcohol use disorder completed baseline assessments and then received an 8-week outpatient treatment that integrates alcohol treatment based on cognitive behavioral methods with breathing-based stress management. | 33 |
| MD/ET Moderate drinkers (controls) with early trauma:
Control participants completed baseline assessments without receiving any outpatient treatment. | 27 |
| MD/NT Moderate drinkers (controls) without early trauma:
Control participants completed baseline assessments without receiving any outpatient treatment. | 37 |
| Total | 131 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | noncompliance | 2 | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | AUD/ET | Total | MD/NT | MD/ET | AUD/NT |
|---|---|---|---|---|---|
| Age, Continuous | 34.1 years STANDARD_DEVIATION 9 | 33.5 years STANDARD_DEVIATION 8.4 | 32.0 years STANDARD_DEVIATION 7.7 | 31.6 years STANDARD_DEVIATION 7.5 | 35.94 years STANDARD_DEVIATION 9.1 |
| Amount of alcohol consumption (weekly) | 18.9 alcohol drinks (weekly) STANDARD_DEVIATION 15.8 | 10.8 alcohol drinks (weekly) STANDARD_DEVIATION 13.6 | 2.2 alcohol drinks (weekly) STANDARD_DEVIATION 2 | 1.9 alcohol drinks (weekly) STANDARD_DEVIATION 2.1 | 19.6 alcohol drinks (weekly) STANDARD_DEVIATION 13.6 |
| Days of alcohol consumption (weekly) | 4.0 days of alcohol use (weekly) STANDARD_DEVIATION 2.2 | 2.6 days of alcohol use (weekly) STANDARD_DEVIATION 2.2 | 1.2 days of alcohol use (weekly) STANDARD_DEVIATION 1 | 0.9 days of alcohol use (weekly) STANDARD_DEVIATION 0.9 | 4.1 days of alcohol use (weekly) STANDARD_DEVIATION 2 |
| Early Trauma Score | 60.2 units on a scale STANDARD_DEVIATION 17.3 | 46.0 units on a scale STANDARD_DEVIATION 18.7 | 30.6 units on a scale STANDARD_DEVIATION 5.8 | 63.3 units on a scale STANDARD_DEVIATION 13.6 | 34.4 units on a scale STANDARD_DEVIATION 6.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 32 Participants | 12 Participants | 7 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 99 Participants | 25 Participants | 20 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 12 Participants | 3 Participants | 5 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 30 Participants | 8 Participants | 6 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 6 Participants | 0 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 9 Participants | 5 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 17 Participants | 72 Participants | 21 Participants | 10 Participants | 24 Participants |
| Region of Enrollment United States | 34 participants | 131 participants | 37 participants | 27 participants | 33 participants |
| Sex: Female, Male Female | 19 Participants | 64 Participants | 16 Participants | 16 Participants | 13 Participants |
| Sex: Female, Male Male | 15 Participants | 67 Participants | 21 Participants | 11 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 33 | 0 / 27 | 0 / 37 |
| other Total, other adverse events | 4 / 34 | 0 / 33 | 0 / 27 | 0 / 37 |
| serious Total, serious adverse events | 0 / 34 | 0 / 33 | 0 / 27 | 0 / 37 |
Outcome results
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.
Time frame: baseline
Population: In AUD/ET, one participant did not complete the fMRI part of the study, resulting in N=33 for brain response. Among them, one participant only completed alcohol cue condition due to discomfort with the MRI scan. In AUD/NT, two participants did not complete the fMRI part of the study, resulting in N=31. In MD/ET, one participant did not complete the stress condition. In MD/NET, one participant did not complete the alcohol condition, and two participants did not complete the stress condition.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AUD/ET | Brain Response | R. VmPFC response to alcohol cue | .071 unitless | Standard Deviation 0.33 |
| AUD/ET | Brain Response | R. VmPFC response to stress cue | .015 unitless | Standard Deviation 0.31 |
| AUD/ET | Brain Response | R. VmPFC response to neutral cue | .042 unitless | Standard Deviation 0.24 |
| AUD/NT | Brain Response | R. VmPFC response to alcohol cue | .058 unitless | Standard Deviation 0.19 |
| AUD/NT | Brain Response | R. VmPFC response to neutral cue | .01 unitless | Standard Deviation 0.31 |
| AUD/NT | Brain Response | R. VmPFC response to stress cue | .010 unitless | Standard Deviation 0.19 |
| MD/ET | Brain Response | R. VmPFC response to stress cue | -.013 unitless | Standard Deviation 0.19 |
| MD/ET | Brain Response | R. VmPFC response to alcohol cue | -.042 unitless | Standard Deviation 0.28 |
| MD/ET | Brain Response | R. VmPFC response to neutral cue | -.091 unitless | Standard Deviation 0.3 |
| MD/NT | Brain Response | R. VmPFC response to alcohol cue | .067 unitless | Standard Deviation 0.022 |
| MD/NT | Brain Response | R. VmPFC response to neutral cue | .017 unitless | Standard Deviation 0.22 |
| MD/NT | Brain Response | R. VmPFC response to stress cue | .08 unitless | Standard Deviation 0.19 |
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.
Time frame: baseline
Population: Among the 33 AUD/ET participants who underwent MRI scans, 3 blood samples were not collected due to nurse unavailability (N=2) and difficult venous access (N=1). In the 31 AUD/NT MRI participants, two samples were not collected due to technical issues. Of the 27 MD/ET, 5 samples were not collected due to nurse unavailability (N=5) and a technical issue (N=1). Of the 37 MD/NT, 6 samples were not collected due to nurse unavailability (N=4), IV tubing issue (N=1), and participant refusal (N=1).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AUD/ET | Stress Hormone Response (Cortisol to ACTH Ratio) | .14 µg/dL per pg/ml | Standard Deviation 0.09 |
| AUD/NT | Stress Hormone Response (Cortisol to ACTH Ratio) | .11 µg/dL per pg/ml | Standard Deviation 0.05 |
| MD/ET | Stress Hormone Response (Cortisol to ACTH Ratio) | .19 µg/dL per pg/ml | Standard Deviation 0.09 |
| MD/NT | Stress Hormone Response (Cortisol to ACTH Ratio) | .17 µg/dL per pg/ml | Standard Deviation 0.11 |
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.
Time frame: up to 90 days
Population: Among the 34 AUD/ET participants, one dropped out before starting treatment, leaving 33 to begin the 8-week intervention. Of these, 29 completed the treatment and follow-up. Among the 33 AUD/NT participants, two dropped out before the treatment, leaving 31 who initiated the treatment. Of these, 28 completed the treatment and two lost to follow-up for this measure. The MD/ET and MD/NT groups did not start treatment therefore no data was collected for the MD groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AUD/ET | Time to Relapse | 22.8 days to first drink after treatment | Standard Deviation 34 |
| AUD/NT | Time to Relapse | 5.6 days to first drink after treatment | Standard Deviation 8.7 |
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.
Time frame: up to 90 days
Population: Among the 34 AUD/ET participants, one dropped out before treatment, leaving 33 to start the intervention, with 29 completing treatment and follow-up (FU). Among the 33 AUD/NT participants, two dropped out before treatment, leaving 31 to initiate the intervention, with 28 completing treatment and three lost to follow-up for this measure (two before the 14-day FU, one before the 90-day FU). The MD/ET and MD/NT groups did not start treatment therefore no data was collected for the MD groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AUD/ET | Amount of Alcohol Consumption (Weekly) | 5.6 alcohol drinks (weekly) | Standard Deviation 8.1 |
| AUD/NT | Amount of Alcohol Consumption (Weekly) | 13.1 alcohol drinks (weekly) | Standard Deviation 8.4 |
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.
Time frame: up to 90 days
Population: Among the 34 AUD/ET participants, one dropped out before treatment, leaving 33 to start the 8-week intervention, with 29 completing treatment and follow-up (FU). Among the 33 AUD/NT participants, two dropped out before treatment, leaving 31 to initiate the intervention, with 28 completing treatment and three lost to follow-up (two before the 14-day FU, one before the 90-day FU). The MD/ET and MD/NT groups did not start treatment therefore no data was collected for the MD groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AUD/ET | Frequency of Alcohol Use (Percentage) | 26.1 Percentage of alcohol use days | Standard Deviation 29.4 |
| AUD/NT | Frequency of Alcohol Use (Percentage) | 45.4 Percentage of alcohol use days | Standard Deviation 25 |