Adverse Childhood Experiences in Substance-related Disorders

Stress Sensitivity, Emotion Processing and Cue-reactivity: the Influence of Adverse Childhood Experiences in Substance-related Disorders

Aversive childhood experiences (ACE) and their relation to the development of an alcohol use disorder will be measured with fMRI.

Study Overview

• Status: Active, not recruiting
• Conditions: Alcohol Use Disorder; Trauma, Psychological
• Intervention / Treatment: Other: No intervention

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. (Neuro-) biological and physiological mechanisms underlying AUD after ACE will be studied.

Neural correlates of stress-sensitivity, emotion processing and alcohol cue-reactivity 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 question whether individuals with AUD and ACE might tend to use alcohol to cope with stress, negative affect or intrusions (according to the self-medication model) will be explored. On the other hand, individuals with AUD and low levels of ACE might use alcohol for its positive effects (according to a positive reinforcement model).

90 individuals (30 HC and 60 individuals with AUD and varying levels of ACE) will be examined using interviews, questionnaires and fMRI tasks as well as saliva and blood samples. All ethical votes and informed consents of participants are and will be obtained according to the declaration of Helsinki.

• Study Type: Observational
• Enrollment (Actual): 70

Contacts and Locations

Study Locations

• Germany
  • Mannheim, Germany
    • Klinik für Abhängiges Verhalten, Zentralinstitut für Seelische Gesundheit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Residents from Mannheim/ Heidelberg who answered an open call to participate in this study

Description

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"
• Healthy individuals (AUDIT Score<=8, alcohol intake < 12g/ less than 5 days (women) & 24g/ less than 5 days (men)
• 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) with up to 28 days of abstinence AND aversive childhood experiences

Exclusion Criteria:

• Withdrawal of the declaration of consent
• Exclusion criteria for an MRI scan (pregnancy, metal implants,...)
• 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 Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Individuals with alcohol use disorder + ACE; Individuals with AUD and varying levels of adverse childhood experiences (ACE)	Other: No intervention; No intervention; Other Names: observational study
Healthy controls; Healthy individuals without AUD	Other: No intervention; No intervention; Other Names: observational study
Individuals with alcohol use disorder, no ACE; Individuals with AUD and no adverse childhood experiences (ACE)	Other: No intervention; No intervention; Other Names: observational study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fMRI to assess group differences in task-specific brain activation patterns: Stress-sensitivity	Stress-sensitivity: stress task (e.g.mental rotation with and without time pressure) with social component within the MRI scanner to assess neural activation patters during the stress-task	fMRI measurement at one day only (day of fMRI experiment)
fMRI to assess group differences in task-specific brain activation patterns: Emotion processing	Emotion-processing: emotional face-/form-matching task to assess neural activation patters of emotion processing	fMRI measurement at one day only (day of fMRI experiment)
fMRI to assess group differences in task-specific brain activation patterns: Alcohol cue-reactivity	Alcohol cue-reactivity: pictures of alcoholic beverages to asses neural alcohol-cue reactivity	fMRI measurement at one day only (day of fMRI experiment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hormonal stress response using salivary cortisol level	Collection of saliva on a subject's regular week-day for the individual's normal cortisol awakening response and circadian rhythm (basal hypothalamic-pituitary-adrenal-function at 0, 0.5, 8 and 14 hours after wake-up). Cortisol awakening reaction, area under the curve and slope will therefore be calculated [nmol/L].	Normal awakening response on a subject's regular week-day (0, 0.5, 8 and 14 hours after wake-up)
Hormonal stress response using salivary cortisol level	Collection of saliva during the course of the fMRI stress task for task-induced stress effects on salivary cortisol levels (at -45, -22, -10 minutes before and 35, 45, 60, 75 and 90 minutes after onset of stress induction). Cortisol: Area under the curve and slope will therefore be calculated [nmol/L].	Stress response during the fMRI stress task (day of fMRI experiment, at -45, -22, -10 minutes before and 35, 45, 60, 75 and 90 minutes after onset of stress induction)
GWAS and especially glutamatergic, serotonergic single-nucleotide polymorphisms	Genomic DNA using 40ml EDTA-blood	blood sample at one day only (day of fMRI experiment)

Collaborators and Investigators

• Sponsor: Central Institute of Mental Health, Mannheim
• Collaborators: German Research Foundation
• Investigators: Principal Investigator: Sabine Vollstaedt-Klein, CIMH Mannheim

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 15, 2018
• Primary Completion (ACTUAL): May 27, 2021
• Study Completion (ANTICIPATED): August 31, 2021

Study Registration Dates

• First Submitted: August 20, 2018
• First Submitted That Met QC Criteria: November 28, 2018
• First Posted (ACTUAL): November 29, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 29, 2021
• Last Update Submitted That Met QC Criteria: July 28, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Substance-Related Disorders; Alcoholism; Psychological Trauma
• Other Study ID Numbers: GRK2350-B5

Drug and device information, study documents

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