Cue Effects in Human Addiction: Pavlovian to Instrumental Transfer

NCT05992272 | Recruiting DMC

• 1 other identifier: 402170461
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Alcohol Use Disorder (AUD); Alcoholism; Substance Use Disorders; Smoking, Tobacco; Stress Reaction; Stress

Keywords

substance use disorder (SUD), cognitive control/interference; alcohol use disorder (AUD); Smokers; general and outcome-specific Pavlovian to instrumental transfer; chronic and acute stress; Amygdala; Stroop Test; Ventral Striatum; Neuroimaging; Humans; Surveys and Questionnaires; Reward; Fractals; Cues

Outcome Measures

Primary Outcomes (14)

• 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

  Day 1

• 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

  Day 2

• 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.

  Day 1

• 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.

  Day 1

• Behavioral PIT effect on velocity day 2

  a subsample of subjects has a second assessment with the PIT paradigm (parallel version) following Stress or Placebo intervention. At this second day the investigators calculate velocity PIT effect only.

  Day 2

• Chronic stress effects on hair cortisol in picogram/milligram

  chronic stress assessment via: \- hair cortisol measurement (3 cm hair segments)

  retrospective assessment before PIT testing at Day 1

• Chronic stress quenstionnaire 1

  chronic stress assessment via: \- Trier Inventory for the Assessment of Chronic Stress (TICS; assessing chronic stress over the last three months, likert scale 0-4, with zero meaning never and four meaning very often; high values stand for more stress))

  retrospective assessment before PIT testing at Day 1

• Chronic stress quenstionnaire 2

  chronic stress assessment via: \- Social Readjustment Rating Scale (SRRS; assessing chronic stress life events of the last year, scaling asking for yes or no. higher values represent more stressful live events over the last year)

  retrospective assessment before PIT testing at Day 1

• Chronic stress quenstionnaire 3

  chronic stress assessment via: \- Perceived Stress Scale (PSS; assessing chronic stress over the last month, likert scale 0-4, with zero meaning never and four meaning very often; high values stand for higher perceived stress)

  retrospective assessment before PIT testing at Day 1

• cognitive control Stroop effect

  Cognitive control assessment via: \- Counting Stroop task

  Day 1

• cognitive control Simon effect

  Cognitive control assessment via: No-go Simon task

  Day 1

• cognitive control interference effect

  Cognitive control assessment via: Stop Signal reaction time task

  Day 1

• Acute stress day 1

  Acute stress inducting using: Trier social stress test (TSST) OR placebo (randomized across days between subjects)

  Day 1

• Acute stress day 2

  Acute stress inducting using: Trier social stress test (TSST) OR placebo (randomized across days between subjects)

  Day 2

Secondary Outcomes (2)

• Saliva cortisol concentration in nmol/litre

  Assessment before, during and after TSST (-60 minutes, 0 minutes, +10 minutes, +20 minutes, +30 minutes,+ 50 minutes, +80 minutes)

• alcohol consumption after 12 months

  12 months after testing for behavioral and neural PIT effects

Study Arms (2)

alcohol use disorder (AUD)

Participants with alcohol use disorder (mild to moderate or severe if no withdrawal symptoms) including: * daily smokers (at least 1 cigarette per day in last 3 months) * non-daily (min 1x/last 3months) * non-smokers

Biological: fMRI imaging (BOLD); Biological: sMRI (structure); Behavioral: Trier Social Stress Test; Behavioral: PIT paradigm; Behavioral: Counting Stroop task; Behavioral: No-go Simon task; Diagnostic Test: Stop Signal Task; Diagnostic Test: blood samples; Diagnostic Test: questionnaires for chronic stress; Diagnostic Test: hair samples; Diagnostic Test: saliva samples; Diagnostic Test: EMA assessment; Diagnostic Test: clinical diagnostic

non-AUD

Participants with a maximum of 1 AUD criteria according to DSM-5, including: * daily smokers (at least 1 cigarette per day in last 3 months) * non-daily (min 1x/last 3months) * non-smokers

Biological: fMRI imaging (BOLD); Biological: sMRI (structure); Behavioral: Trier Social Stress Test; Behavioral: PIT paradigm; Behavioral: Counting Stroop task; Behavioral: No-go Simon task; Diagnostic Test: Stop Signal Task; Diagnostic Test: blood samples; Diagnostic Test: questionnaires for chronic stress; Diagnostic Test: hair samples; Diagnostic Test: saliva samples; Diagnostic Test: clinical diagnostic

Interventions

fMRI imaging (BOLD) BIOLOGICAL

Will 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.

alcohol use disorder (AUD); non-AUD

sMRI (structure) BIOLOGICAL

Will be used to investigate neural correlates of PIT effects by identifying abnormalities in cortical gray and white matter volume.

alcohol use disorder (AUD); non-AUD

Trier Social Stress Test BEHAVIORAL

Will 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.

alcohol use disorder (AUD); non-AUD

PIT paradigm BEHAVIORAL

The 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.

alcohol use disorder (AUD); non-AUD

Counting Stroop task BEHAVIORAL

Will 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

alcohol use disorder (AUD); non-AUD

No-go Simon task BEHAVIORAL

Will 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.

alcohol use disorder (AUD); non-AUD

Stop Signal Task DIAGNOSTIC_TEST

Will 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.

alcohol use disorder (AUD); non-AUD

blood samples DIAGNOSTIC_TEST

for genetic and epigenetic testing, especially for exploratory outcome prediction using polygenic risk scores.

alcohol use disorder (AUD); non-AUD

questionnaires for chronic stress DIAGNOSTIC_TEST

* Perceived Stress Scale * Social Readjustment Rating Scale * Trier Inventory for the Assessment of Chronic

alcohol use disorder (AUD); non-AUD

hair samples DIAGNOSTIC_TEST

Hair cortisol measurement (3 cm hair segments) will be used to assess chronic stress.

alcohol use disorder (AUD); non-AUD

saliva samples DIAGNOSTIC_TEST

Assessing acute stress effects in AUD.

alcohol use disorder (AUD); non-AUD

EMA assessment DIAGNOSTIC_TEST

We 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).

alcohol use disorder (AUD)

clinical diagnostic DIAGNOSTIC_TEST

SKID-I Interview neurocognitive and psychopathological testing

alcohol use disorder (AUD); non-AUD

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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
• Ability to consent to the study and complete the questionnaires
• Sufficient language skills: German
• Availability between 3pm-6pm on 2 consecutive days (Experiment 1, acute stress question)
• Females only: luteal phase (Experiment 1, acute stress question)

You may not qualify if:

• 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
• Ingestion of medications known to interact with the CNS in the 10-day period prior to study participation or less than 4 half-lives after last ingestion (rapid urine test)
• MR contraindications (e.g., pacemakers, metallic or electronic implants, metallic splinters, surgical staples)
• Color vision deficiency
• Sensorineural hearing loss of 30 dB or greater,
• Tinnitus
• Presence of claustrophobia
• Acute alcohol intoxication at MRI appointments verified by breath alcohol testing or drug intoxication verified by rapid urine testing
• For women only: not peri- or postmenopausal, not taking contraceptives (Experiment 1, acute stress question)

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• Technische Universität Dresden: collaborator

Study Sites (2)

Charite - Universitätsmedizin Berlin

Berlin, 10117, Germany

RECRUITING

Technische Universität Dresden

Dresden, 01307, Germany

RECRUITING

Related Publications (1)

• Belanger MJ, Chen H, Hentschel A, Garbusow M, Ebrahimi C, Knorr FG, Zech HG, Pilhatsch M, Heinz A, Smolka MN. Development of Novel Tasks to Assess Outcome-Specific and General Pavlovian-to-Instrumental Transfer in Humans. Neuropsychobiology. 2022;81(5):370-386. doi: 10.1159/000526774. Epub 2022 Nov 14.

  PMID: 36380640 RESULT

MeSH Terms

Conditions

Alcoholism; Substance-Related Disorders; Tobacco Smoking; Fractures, Stress; Bronchiolitis Obliterans Syndrome

Interventions

Psychological Tests; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Smoking; Behavior; Tobacco Use; Fractures, Bone; Wounds and Injuries; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Intervention Hierarchy (Ancestors)

Behavioral Disciplines and Activities; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Andreas Heinz, Prof., MD, PhD

CONTACT

0049 30 450 517 001; andreas.heinz@charite.de

Maximilian Pilhatsch, MD, PhD

CONTACT

0049 (351) 458 19312; max.pilhatsch@uniklinikum-dresden.de

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: head of Department of Psychiatry and Psychotherapy | CCM, principle investigator

Study Record Dates

• First Submitted: June 30, 2023
• First Posted: August 15, 2023
• Study Start: November 24, 2020
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: August 21, 2024

Record last verified: 2024-08

Locations

DE (2)