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).

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.

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

Patients from the Addiction Clinic at the Central Institute of Mental Health (Mannheim, Germany), as well as residents predominantly from the Mannheim/Heidelberg area who answered an open call to participate in this study.