Stress-related Predictor Profiles in Human Addiction

Study Overview
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Brief Summary
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Long-term aim is the definition of a setup of mobile sensors and their integration in a mobile infrastructure that allows the prediction of stress related alcohol intake in an ambulatory setting. Here, we aim to identify stress- and alcohol cue-related physiological markers in a lab experiment to assess interactions between acute psychological vs. physical stress exposure and alcohol cue-exposure regarding their effects on measures relevant for the development and maintenance of Alcohol Use Disorder (AUD). Further, we aim to identify neural correlates in brain circuits of motivational, cognitive, and affective processing. In addition to applying established stress-related markers, we will integrate innovative sensor-based measures.

Detailed Description
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In patients with Alcohol Use Disorder (AUD) stress exposure is known to affect craving, cue-reactivity and relapse risk. Here, we aim to identify stress- and alcohol cue-related physiological markers in a lab experiment to assess interactions between acute psychological vs. physical stress exposure and alcohol cue-exposure regarding their effects on (1) alcohol craving and related markers (attentional bias to alcohol-cues, implicit association task, neural cue-reactivity), (2) their predictive capacity for future alcohol intake, (3) the identification their neural correlates in brain circuits of motivational, cognitive, and affective processing. In addition to applying established stress-related markers (cortisol in saliva, heart-rate variability, systolic blood pressure and electrodermal activity), (4) we will integrate portable sensors (wearables) to allow a future integration in ambulatory assessments and to test innovative measures currently under investigation (e.g. voice stress analysis) to identify whether these additional parameters increase the predictive significance. Our long-term aim is the definition of a setup of mobile sensors and their integration in a mobile infrastructure that allows the prediction of stress related alcohol intake in an ambulatory setting.

Official Title
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Stress-related Predictor Profiles for Craving and Relapse in Human Addiction

Conditions
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Craving, Alcohol Use Disorder, Stress Reaction, Social Stress, Relapse, Addiction, Risk Behavior

Intervention / Treatment
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* Behavioral: Trier Social Stress Test
* Behavioral: Ergometer
* Behavioral: Barlab-Exposure
* Behavioral: Reading Newspaper


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Alcohol-use disorder according to 2 DSM-V criteria not requiring detoxification: AUD subjects with mild AUD will fulfill at least 2 and not more than 5 diagnostic criteria; a second group of AUD subjects will fulfill 4-5 criteria for moderate AUD sufficient ability to communicate with the investigators, to answer questions in oral and written form fully informed consent written informed consent Exclusion Criteria: withdrawal of the declaration of consent Pregnancy Using hormonal contraceptives Perimenopausal/ postmenopausal positive urin drug screening (cannabis, amphetamine, opiates, benzodiazepines, cocaine) Lifetime history of DSM-5 bipolar disorder, schizophrenia or schizophrenia spectrum disorder, or substance dependence other than alcohol or nicotine or cannabis dependence. Current threshold DSM-5 diagnosis of major depressive disorder, or presence of suicidal intention History of severe head trauma or other severe central nervous system disorder (e.g., dementia, Parkinson's disease, multiple sclerosis) Current use of medications or drugs known to interact with the CNS within at least four half-lives post last intake

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control<br>Participants reads newspaper before Barlab-Exposure | Behavioral: Barlab-Exposure<br>* Participants are exposed to a bar situation with different sorts of alcohol available. They sniff at water and at one alcoholic drink.<br>Behavioral: Reading Newspaper<br>* Participants read newspaper<br>|
| Experimental: Experimental 1 (Distress)<br>Participants undergo the Trier Social Stress Test before Barlab-Exposure | Behavioral: Trier Social Stress Test<br>* Test to induce high levels of acute social stress, including actors and a faked exam situation<br>Behavioral: Barlab-Exposure<br>* Participants are exposed to a bar situation with different sorts of alcohol available. They sniff at water and at one alcoholic drink.<br>|
| Experimental: Experimental 2 (Eustress)<br>Participants ride an ergometer before Barlab-Exposure | Behavioral: Ergometer<br>* Riding ergometer<br>Behavioral: Barlab-Exposure<br>* Participants are exposed to a bar situation with different sorts of alcohol available. They sniff at water and at one alcoholic drink.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in heart rate | heart rate acquired with ear clip (continuous time series) | at examination day: continuous measurement throughout the whole experiment (except during MRI scanning); duration around 2 hours; starting 1 hour 50 minutes after arrival of the proband | 
| change in heart rate variability | heart rate variability acquired with ear clip (continuous time series) | at examination day: continuous measurement throughout the whole experiment (except during MRI scanning); duration around 2 hour; starting 1 hour 50 minutes after arrival of the proband | 
| change in blood pressure (systolic and diastolic) | acquired with pressure sleeve | at examination day: 6 time points measured throughout the whole experiment (except during MRI scanning); at hours:minutes 2:20, 2:50, 3:20, 3:50, 4:50, 5:05 after arrival of the proband | 
| change in electrodermal activity | time series acquired with body sensor | at examination day: continuous measurement throughout the whole experiment (except during MRI scanning); duration around 2 hour; starting 1h 50min after arrival of the proband | 
| neural alcohol-related cue-reactivity | % signal change, measured with fMRI; paradigm Vollstädt-Klein et al. 2010; [% signal change is not a change over time; it is measured during one experimental session] | at examination day: measured directly after the behavioral tasks at the end of the lab experiment | 
| neural inhibition processing | % signal change, measured with fMRI; stop-signal reaction time task (Fauth-Buhler et al. 2012) [% signal change is not a change over time; it is measured during one experimental session] | at examination day: measured directly after the behavioral tasks at the end of the lab experiment | 
| neural emotion processing | % signal change, measured with fMRI; faces task (Hariri et al. 2002) [% signal change is not a change over time; it is measured during one experimental session] | at examination day: measured directly after the behavioral tasks at the end of the lab experiment | 
| resting state activity | resting state connectivity measured with fMRI | at examination day: measured directly after the behavioral tasks at the end of the lab experiment | 
| fMRI | neural alcohol-related cue-reactivity, stop-signal reaction time task, emotion processing and resting state fMRI | at examination day: measured directly after the behavioral tasks at the end of the lab experiment | 
| attentional bias to alcohol cues | measured with reaction time differences (in milliseconds) using the dotprobe-task (Vollstädt-Klein et al. 2009) [reaction time differences is not a change over time; it is measured during one experimental session] | at examination day: measured directly after the stress task / newspaper reading; before implicit alcohol association and MRI session | 
| implicit alcohol association | measured with reaction time differences (in milliseconds) using the implicit association task (Wiers et al. 2016) [reaction time differences is not a change over time; it is measured during one experimental session] | at examination day: measured after the stress task / newspaper reading, directly after the attentional bias to alcohol cues ; before MRI session | 
| change in level of cortisol | cortisol measured in saliva as a stress marker | at examination day: 6 time points measured throughout the whole experiment (except during MRI scanning); at hours:minutes 2:20, 2:50, 3:20, 3:50, 4:50, 5:05 after arrival of the proband | 
| change in voice stress pattern | audio file of participants' voice for voice stress pattern analysis will be recorded. From this a multivariate measure (i.e. multivariate vector) will be acquired (including frequency, loudness etc.) | at examination day: 6 time points measured throughout the whole experiment (except during MRI scanning); at hours:minutes 2:20, 2:50, 3:20, 3:50, 4:50, 5:05 after arrival of the proband | 
| change in alcohol urges | self-report questionnaire: Alcohol Urge Questionnaire (AUQ); Bohn et al. 1995 | at examination day: 6 time points measured throughout the whole experiment (except during MRI scanning); at hours:minutes 2:20, 2:50, 3:20, 3:50, 4:50, 5:05 after arrival of the proband | 
| change in alcohol craving | self-report How strong is your craving for alcohol?: reported on a visual analogue scale ranging from 0 to 100 | at examination day: 6 time points measured throughout the whole experiment (except during MRI scanning); at hours:minutes 2:20, 2:50, 3:20, 3:50, 4:50, 5:05 after arrival of the proband | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| alcohol consumption | self-report using the instrument Form90 (Scheurich et al. 2005) | 12 months follow-up |