Neurobehavioral Profiles of Adaptive Stress Responses in Individuals With Alcohol Use Disorder

Towards Neurobehavioral Profiles and Models of Adaptive Stress Responses and Resilience in Individuals With Alcohol Use Disorder

The goal of this observational study is to investigate longitudinal stress response profiles and adaptive versus non-adaptive stress responses in alcohol use disorder. The main questions the projects aims to answer are:

What are the neurobehavioral underpinnings of adaptive stress responses and resilience to repeated stress exposure with regards to:

• alcohol craving?
• alcohol use?
• their modulation by prior stress exposure, social interactions, coping strategies and individual health behavior?

Participants will:

• be exposed to an established experimental stress-induction protocol, the Trier Social Stress Test
• be exposed to their favorite drink in a bar lab environment
• be assessed using fMRI to determine their neural alcohol cue reactivity, response inhibition, and emotion processing
• conduct an ambulatory phase to assess stressors, alcohol craving, substance use and details on social interactions, health behavior and coping strategies using ecological momentary assessment tools.

The main objective of the study is to identify longitudinal profiles and models of adaptive stress responses and stress resilience in individuals with alcohol use disorder (AUD) and understand how stress and different responses to it influence alcohol craving and alcohol use trajectories over time. To achieve these goals, the investigators will examine habituation vs. sensitization of cortisol responses to repeated experimental stress exposure in individuals with AUD, as an established experimental model to studying adaptive vs. non-adaptive stress responses in the framework of an experimental set-up including an initial rest period (30 minutes), followed by the Trier Social Stress Test (15 minutes), exposure to the favorite drink in a bar environment (9 minutes) and functional magnetic resonance imaging (75 minutes) assessing A) neural alcohol cue-reactivity, B) inhibition performance during a Stop Signal Task, C) emotion processing during a face-matching task and D) resting state connectivity. The investigators also seek to characterize the neurobehavioral underpinnings of sensitized vs. habituated responses to repeated stress exposure, using an established alcohol cue-reactivity fMRI paradigm, and determine the impact of sensitized vs. habituated stress responses on physiological and subjective stress markers, alcohol craving, alcohol use, as well as their modulation by prior stress exposure, social support, drinking goals and individual health behavior with a focus on potentially modifiable factors that could serve as targets for future ecological momentary interventions. This setup will be repeated on a second examination day.

In addition, the investigators aim to assess whether the observed habituation vs. sensitization phenotypes to repeated stress exposure translate into everyday-life of the respective individual and predict adaptive vs. non-adaptive stress responses. To this end, the investigators will acquire ambulatory assessments with high temporal resolution over six weeks, including detailed mapping of exposure to micro- and macro-stressors, drinking motifs, alcohol craving, alcohol use and data on factors that potentially modify the association between stress and alcohol use, such as social interactions, stress coping strategies, drinking goals and individual health behavior (e.g., sleep, physical activity) to assess whether the observed habituation vs. sensitization phenotypes to repeated stress exposure translate into everyday-life of the respective individual and predict real-life stress responses and alcohol use.

Study flow:

Screening (telephone): Assessing study eligibility

Experimental study visit 1: Rest period (30 minutes) - Trier Social Stress Test (15 minutes) - Alcohol cue exposure (9 minutes) - fMRI (75 minutes)

Experimental study visit 2: Repetition of setup from 'experimental study visit 1'

Following six weeks: Ambulatory phase (smartphone tool) with daily requests regarding stressors, alcohol craving and consumption as well as health behavior

Inclusion criteria are:

• age between 16 and 65 years
• meeting at least 2 criteria of an alcohol use disorder according to the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5), yet without the need for a therapeutic intervention
• fluency in German
• able to understand the study procedures and give informed consent
• willingness to use a study smartphone

Exclusion criteria are:

• current use of drugs or medications that interact with the central nervous system or the glucocorticoid system
• contraindications for magnetic resonance imaging
• medical history of bipolar disorder, psychotic disorder, schizophrenia or schizophrenic spectrum disorder, or substance use disorder other than alcohol, nicotine, or cannabis
• medical history of severe head injury or other severe central nervous system disorders or other severe somatic disorders (e.g. liver cirrhosis)
• pregnancy