Individuals with substance use disorders (SUD) have to cope with drug-related cues and contexts, which can affect instrumental drug seeking as shown with Pavlovian to instrumental transfer (PIT) paradigms in animals and humans. The investigators aimed to investigate the impact of acute and chronic stress on Pavlovian-to-instrumental transfer (PIT), how PIT it is associated with cognitive control abilities and whether such effects predict losing vs. regaining control in subjects with AUD. Moreover, the investigators aimed to develop a novel full transfer task that assesses both, general and specific PIT to investigate whether specific PIT differs between alcohol use disorder (AUD) and control subjects.
males and females between 16-65 years of age
AUD subjects only: meet a minimum of 2 criteria for DSM-5 alcohol-related disorder (AUD) (not requiring withdrawal as assessed by an independent psychiatrist) and AUDIT > 4
Smokers: Daily smokers only: smoke 7 days/week during the last three months
Non-daily smokers only: smoke at least once but less than 7 days/week during the last three months
Lifetime diagnosis according to DMS-5 for: Bipolar disorder, schizophrenia, schizophrenia spectrum disorder, substance dependence except for alcohol, nicotine, or cannabis
Currently meeting DSM-5 diagnostic criteria for a depressive episode, suicidal ideation
Past traumatic brain injury or severe neurological disease (such as dementia, Parkinson's disease, multiple sclerosis)
Pregnancy or breastfeeding
All groups will be recruited from general population via advertisement (e.g. ebay Kleinanzeigen, Facebook) and notes (e.g. blackbords, intranet) in Berlin and Dresden
Case-control
Retrospective
fMRI imaging (BOLD)
Biological/VaccineWill be used to investigate neural correlates of PIT effects by measuring the blood oxygenation level dependent (BOLD) response of neural activation in the mesolimbic system.
sMRI (structure)
Biological/VaccineWill be used to investigate neural correlates of PIT effects by identifying abnormalities in cortical gray and white matter volume.
Trier Social Stress Test
BehavioralWill be used to assess the effect of acute stress induction on behavioral and neural PIT effects. The induced stress is generated in a social context, where the participants are asked to prepare a job interview for their dream job and to present it in front of a three-member jury.
PIT paradigm
BehavioralThe paradigm consists of four parts: In the first part, an instrumental learning task is completed in which subjects must learn which stimuli require a response and which do not. In the second part, a classical (Pavlovian) conditioning task is then completed in which subjects learn by passive viewing which stimuli are associated with certain amounts of money. The third part measures to which instrumental responses (learned in Part 1) are modulated by the presentation of the classically conditioned stimuli (learned in Part 2). At the same time drug-associated stimuli are presented in the background measuring to which extent they conflict with the learned instrumental behavior. In the last part, query trials are implemented in which the participants have to choose between two pictures to assess the relative cue value.
Counting Stroop task
BehavioralWill be used to assess interference at stimulus level. Here either one, two, three or four identical digits from 1 to 4 are shown. Number and denotation of digits are either congruent (1, 22, 333, 4444; 88 trials) or incongruent (111, 2222, 3, 4444; 88 trials). Subjects have to indicate how many digits were shown
No-go Simon task
BehavioralWill be used to measure interference at the response level and response inhibition. We will show arrows either pointing to the left or right. The arrow can either be shown on the left or the right side of the display. In congruent trials, direction and position are the same, whereas they differ in incongruent trials. Participants have to indicate the direction of the arrow and ignore the position.
Stop Signal Task
Diagnostic testWill be used to examine inhibitory control. The participants tap the left and right side of the screen to smash two falling fruits. When the fruits pass two circles, subjects are required to tap both sides of the screen. In "stop trials" one of the fruits turns brown (rotten), indicating the corresponding side of the screen should not be tapped.
blood samples
Diagnostic testfor genetic and epigenetic testing, especially for exploratory outcome prediction using polygenic risk scores.
questionnaires for chronic stress
Diagnostic test* Perceived Stress Scale * Social Readjustment Rating Scale * Trier Inventory for the Assessment of Chronic
hair samples
Diagnostic testHair cortisol measurement (3 cm hair segments) will be used to assess chronic stress.
saliva samples
Diagnostic testAssessing acute stress effects in AUD.
EMA assessment
Diagnostic testWe will use smartphones with additional mobile sensors (wearables), which will be used to measure physical activity, data on location (GPS), geolocation-based triggering of e-Diaries, self-reported stress reactivity, cue exposure (encounters with drug-related stimuli in real life), drug craving, impulsivity and drug consumption (priming doses, binges and continuous use of all drugs of abuse).
clinical diagnostic
Diagnostic testSKID-I Interview neurocognitive and psychopathological testing
Neural PIT effect day 1
blood oxygenation level dependent (BOLD) response, investigation of neuronal activation of the mesolimbic system in AUD patients and controls using 3 Tesla magnetic resonance imaging following Stress or Placebo intervention OR no intervention
Neural PIT effect day 2
a subsample of subjects has a second assessment with blood oxygenation level dependent (BOLD) response, investigation of neuronal activation of the mesolimbic system in AUD patients and controls using 3 Tesla magnetic resonance imaging following Stress or Placebo intervention
Behavioral PIT effect on performance day 1
strength of PIT effect assessed with the PIT paradigm. Performance (correct choices) will be recorded. Stronger PIT effects are associated with higher performance (percent correct choices) in congruent versus lower performance in incongruent trials.
Behavioral PIT effect on velocity day 1
strength of PIT effect assessed with the PIT paradigm. Velocity will be recorded. Stronger PIT effects are associated with higher velocity in conditions with positively valued background stimuli and lower velocity with negatively valued background stimuli.
Saliva cortisol concentration in nmol/litre
Acute stress effects in AUD and HC
alcohol consumption after 12 months
alcohol drinking amount (quantity, frequency) during a follow-up period of 12 months
Click on the lead sponsor to view all of their trials.
Charite University, Berlin, Germany
Lead sponsor
Technische Universität Dresden
Collaborator
