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Adverse Childhood Experiences in Alcohol Use Disorder

Completed
Conditions
Alcohol Use Disorder
Trauma, Psychological
Interventions
Other: No intervention
Registration Number
NCT05048758
Lead Sponsor
Central Institute of Mental Health, Mannheim
Brief Summary

Adverse childhood experiences (ACE) and their relation to the development of an alcohol use disorder (AUD) will be measured with functional magnetic resonance imaging (fMRI).

Detailed Description

The aim of this study is to examine the impact of ACE on stress sensitivity, cue-reactivity, and emotion processing in individuals with AUD at a longitudinal level. For this, participants (excluding healthy controls) from the first project (see https://clinicaltrials.gov/ct2/show/NCT03758053) will be re-examined after 2 to 2.5 years to explore the involvement of these mechanisms in relation to (long-term) relapse risk, which is a central issue in substance use disorders. Furthermore, we will investigate cognitive functions, specifically response inhibition and working memory, in the relationship between ACE and AUD. Additional participants may be recruited to mitigate sample attrition from the first project and to achieve the desired sample size. To assess cognitive functions and data from new participants in relation to relapse risk, we will perform a 3-month follow-up.

Neural correlates of stress-sensitivity, emotion processing, alcohol cue-reactivity and cognitive functions will be assessed using fMRI. Furthermore, blood and saliva samples will be used to assess biological and physiological mechanisms (e.g. salivary cortisol level or genetic markers of AUD and possible gene-environment-interactions).

The current project is interested in the extent to which ACE severity modulates neural activation in specific brain regions during the execution of fMRI paradigms as well as alcohol-related measures (e.g., craving and alcohol consumption). Of particular interest is the question whether these neural and alcohol-related measures are associated with relapse risk.

55 individuals with AUD and varying levels of ACE will be examined using interviews, questionnaires, fMRI tasks as well as saliva and blood samples. Update from 29/03/2023: the relationships of interest will be examined using a dimensional approach to the predictor variable (ACE). Thus, participants will not be divided into two groups (no or mild ACE vs. moderate to severe ACE) as originally planned, but will instead be treated as one group with varying levels of ACE. The new sample size (n = 55) is based on an updated sample size calculation for a linear regression (two-tailed) using the following input parameters: f² = 0.15 (moderate effect size), alpha error = 0.05, and power = 80%. All ethical votes and informed consents of participants will be obtained according to the declaration of Helsinki.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
43
Inclusion Criteria
  • Male and female
  • Age between 18 and 65
  • Normal or correctable eyesight
  • Sufficient ability to communicate with the investigators, to answer questions in oral and written form
  • "Fully Informed Consent"
  • "Written Informed Consent"
  • Individuals with alcohol use disorder according to DSM-5 or 'heavy drinking' (alcohol intake > 40g/ more than 5 days (women) & 60g/ more than 5 days (men) and varying levels of adverse childhood experiences
Exclusion Criteria
  • Withdrawal of the declaration of consent
  • Exclusion criteria for an MRI scan (pregnancy, metal implants, etc.)
  • Severe internal, neurological and psychiatric comorbidities
  • Pharmacotherapy with psychoactive substances within the last 14 days (except treatment with SSRI/SNRIs for at least 28 days)
  • Axis-I disorder according to ICD-10 and DSM 5 (except tobacco and alcohol use disorder, substance abuse with less than 2(11) criteria according to DSM-5, mild depressive episode, adaptation disorder and specific phobia within the last 12 months)
  • Positive urin drug screening (cannabis, amphetamine, opiates, benzodiazepines, cocaine)
  • Withdrawal symptoms (CIWA-R > 7)
  • Intoxication at time of investigation (breathalyzer > 0.3‰)
  • Suicidal tendency or potential danger for others

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Individuals with AUD + varying levels of ACENo interventionIndividuals with alcohol use disorder (AUD) and varying levels of adverse childhood experiences (ACE)
Primary Outcome Measures
NameTimeMethod
fMRI to assess group and within-subjects differences in task-specific brain activation patterns: Stress-sensitivityfMRI measurement at one day only (day of fMRI experiment)

Stress-sensitivity: Imaging Stress Task to assess neural activation patterns during mental arithmetic tasks with negative feedback

fMRI to assess group differences in task-specific brain activation patterns: Working memoryfMRI measurement at one day only (day of fMRI experiment)

Working memory: n-back task (continuous performance) to assess working memory function.

fMRI to assess group and within-subjects differences in task-specific brain activation patterns: Emotion processingfMRI measurement at one day only (day of fMRI experiment)

Emotion-processing: emotional face-/form-matching task to assess neural activation patters of emotion processing

fMRI to assess group differences in task-specific brain activation patterns: Response inhibitionfMRI measurement at one day only (day of fMRI experiment)

Response inhibition: Stop Signal Task (variation of go/no-go) to assess response inhibition.

Long-term alcohol consumption2 - 2.5 year follow-up after first project

Self-report in longitudinal sample measured with the LDH interview

Short-term alcohol consumption3-month follow-up after current project

Self-report in whole sample measured with the Form 90 interview

fMRI to assess group and within-subjects differences in task-specific brain activation patterns: Alcohol cue-reactivityfMRI measurement at one day only (day of fMRI experiment)

Alcohol cue-reactivity: pictures of alcoholic beverages to assess neural alcohol-cue reactivity

Secondary Outcome Measures
NameTimeMethod
Hormonal stress response using salivary cortisol levelday of fMRI experiment, at -45, -22, -10 minutes before and 35, 45, 60, 75 and 90 minutes after onset of stress induction

Time course of salivary cortisol level. Area under the curve and slope will be calculated \[nmol/L\]

GWAS and especially glutamatergic, serotonergic single-nucleotide polymorphismsBlood sample at one day only (day of fMRI experiment)

Genomic DNA using 40ml EDTA-blood

Trial Locations

Locations (1)

Klinik für Abhängiges Verhalten, Zentralinstitut für Seelische Gesundheit

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Mannheim, Baden-Württemberg, Germany

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