xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05992272</url>
    </required_header>
    <id_info>
      <org_study_id>402170461</org_study_id>
      <nct_id>NCT05992272</nct_id>
    </id_info>
    <brief_title>Cue Effects in Human Addiction: Pavlovian to Instrumental Transfer</brief_title>
    <acronym>ReCoDe</acronym>
    <official_title>Cue Effects in Human Addiction: Pavlovian to Instrumental Transfer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Charite University, Berlin, Germany</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Technische Universität Dresden</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Charite University, Berlin, Germany</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Individuals with substance use disorders (SUD) have to cope with drug-related cues and&#xD;
        contexts, which can affect instrumental drug seeking as shown with Pavlovian to instrumental&#xD;
        transfer (PIT) paradigms in animals and humans. The investigators aimed to investigate the&#xD;
        impact of acute and chronic stress on Pavlovian-to-instrumental transfer (PIT), how PIT it is&#xD;
        associated with cognitive control abilities and whether such effects predict losing vs.&#xD;
        regaining control in subjects with AUD. Moreover, the investigators aimed to develop a novel&#xD;
        full transfer task that assesses both, general and specific PIT to investigate whether&#xD;
        specific PIT differs between alcohol use disorder (AUD) and control subjects.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This project has four research aims:&#xD;
  &#xD;
          1. The investigators want to assess the effects of acute as well as repeated stress&#xD;
             exposure on PIT and its neuroimaging correlates, and the investigators will test whether&#xD;
             modulation of PIT by stress predicts losing vs. regaining control of drug intake in mild&#xD;
             to moderate AUD subjects.&#xD;
  &#xD;
          2. The investigators will investigate how cognitive control abilities (e.g. interference&#xD;
             control and response inhibition) are related to the costs of interference between&#xD;
             Pavlovian and instrumental control in PIT.&#xD;
  &#xD;
          3. The investigators will compare PIT, its relation to cognitive control, and the neural&#xD;
             mechanisms between different drugs of abuse by investigating participants with AUD and&#xD;
             also smokers.&#xD;
  &#xD;
          4. The investigators will develop an outcome-specific PIT paradigm with alternative (food)&#xD;
             and drug rewards to compare AUD and healthy controls, and the investigators will explore&#xD;
             communalities and differences in behavioral and neural processes between general PIT and&#xD;
             outcome-specific PIT.&#xD;
  &#xD;
        Therefore, the investigators conduct 3 Experiments with the following Hypotheses:&#xD;
  &#xD;
        Experiment 1:&#xD;
  &#xD;
        Here the investigators assess on a behavioral and neural level a general PIT task that&#xD;
        consists of four parts:&#xD;
  &#xD;
        In the instrumental part, participants have to learn which shells to collect or leave in&#xD;
        order to gain as much money as possible; the correct choice is probabilistically rewarded in&#xD;
        80% of all times. Absolutely unrelated to this instrumental part, during Pavlovian&#xD;
        conditioning colorful fractals are presented in the back of the screen, which have been&#xD;
        passively paired either with monetary gain, no change or monetary loss, i.e. they act as&#xD;
        positively valued, neutral or negatively valued cues. These fractals thus act as independent,&#xD;
        Pavlovian conditioned background stimuli and interact with instrumental behavior in the&#xD;
        unrelated third transfer part of the PIT task. Also, the investigators assess the effects of&#xD;
        drug-specific cues in the background on instrumental behavior during this transfer part. To&#xD;
        avoid further learning, the transfer part will be conducted under nominal extinction.&#xD;
        Finally, query trials, in which participants will have to choose one of two pictures will to&#xD;
        assess the relative cue value.&#xD;
  &#xD;
        Acute stress will be induced by the Trier Social Stress Test (TSST), chronic stress will be&#xD;
        assessed by questionnaires and hair cortisol.&#xD;
  &#xD;
        Hypothesis 1a:&#xD;
  &#xD;
        Acute and chronic stress exposure increase behavioral and neural PIT effects elicited by&#xD;
        monetary Pavlovian conditioned stimuli (CS) and decrease inhibitory effects of alcohol&#xD;
        Pavlovian CS. Functional correlates of PIT effects will be found in the amygdala and in the&#xD;
        ventral striatum.&#xD;
  &#xD;
        Hypothesis 1b:&#xD;
  &#xD;
        Following stress exposure, high PIT effects elicited by monetary Pavlovian CS and low&#xD;
        inhibitory effects elicited by alcohol Pavlovian CS predict higher subsequent alcohol intake&#xD;
        in the follow-up period of 6 months.&#xD;
  &#xD;
        Methods:&#xD;
  &#xD;
        Between group analysis: The investigators will analyze on a behavioral and imaging level how&#xD;
        acutely consuming AUD subjects and matched controls differ regarding money- and&#xD;
        alcohol-related PIT.&#xD;
  &#xD;
        Within-group analysis: The investigators will analyze how acute stress affects PIT effects.&#xD;
        This 2x2 design (1 within-group subject factor with two levels: STRESS vs. NO STRESS and 1&#xD;
        between-group subject factor with two levels: AUD vs. matched controls) will be tested on a&#xD;
        behavioral and neural level.&#xD;
  &#xD;
        Experiment 2:&#xD;
  &#xD;
        In this experiment, the investigators will utilize a 2x3 factorial group design. Participants&#xD;
        will be categorized into two main groups: those with AUD and those without (non-AUD). Each of&#xD;
        these groups will be further divided into three subgroups: daily smokers, non-daily smokers&#xD;
        and non-smokers. Each cell (individual subgroup) will consist of 35 subjects. In addition to&#xD;
        the PIT task described above, the N = 210 participants will additionally perform a Counting&#xD;
        Stroop task and a No-go Simon task. Participants will also perform a stop signal task during&#xD;
        functional MRI (fMRI).&#xD;
  &#xD;
        Methods:&#xD;
  &#xD;
        Interference Costs: Interference costs will be calculated based on error rate (ER) and&#xD;
        reaction time (RT) differences between task conditions, e.g., incongruent vs. congruent&#xD;
        conditions.&#xD;
  &#xD;
        Between-group analysis: the investigators will examine group differences in the interference&#xD;
        PIT effect at both the behavioral and neural levels using a two (AUD vs. non-AUD) by three&#xD;
        (daily smokers vs. non-daily smokers vs. non-smokers) design. In addition, the investigators&#xD;
        aim to investigate the associations between the interference PIT effect and other continuous&#xD;
        measures: Alcohol Use Disorders Identification Test (AUDIT), Fagerström Test for Nicotine&#xD;
        Dependence (FTND), along with quantity-frequency indices.&#xD;
  &#xD;
        Other analysis: In order to gain a better understanding of the mechanisms underlying PIT, the&#xD;
        investigators will also fit a drift diffusion model to the behavioral data and explore the&#xD;
        connectivity within the neural networks during PIT in relation to the connectivity during the&#xD;
        stop signal task (response inhibition).&#xD;
  &#xD;
        Hypothesis 2a:&#xD;
  &#xD;
        Interference costs (i.e. increased error rate [ER] in instrumental responses) during PIT are&#xD;
        associated with interference costs at the stimulus level (Stroop task) and at the response&#xD;
        level (No-go Simon task), and these costs will also be correlated with the ER during response&#xD;
        inhibition (No-go Simon task).&#xD;
  &#xD;
        Hypothesis 2b:&#xD;
  &#xD;
        The investigators hypothesize that the interference PIT effect will be more pronounced in the&#xD;
        AUD group compared to the non-AUD group. The investigators also anticipate that the effect&#xD;
        will be stronger in the smoker group. Furthermore, the investigators hypothesize a positive&#xD;
        correlation between the PIT effect and AUDIT, FTND scores, as well as the quantity and&#xD;
        frequency of use. As the behavioral PIT effect intensifies, the investigators expect&#xD;
        corresponding neural responses to similarly increase.&#xD;
  &#xD;
        Experiment 3:&#xD;
  &#xD;
        The investigators here use a newly-developed full PIT paradigm that introduces primary&#xD;
        reinforcers, i.e. alcoholic and soft drinks (that the investigators administer on a&#xD;
        trial-by-trial basis). Furthermore, the investigators implemented additional Pavlovian&#xD;
        stimuli to examine both general and outcome-specific PIT effects. General PIT effects occur&#xD;
        when positively valued environmental Pavlovian stimuli enhance instrumental responding&#xD;
        regardless of the reinforcer being used. Here, stimuli that are associated with e.g. monetary&#xD;
        rewards can enhance instrumental responding for alcohol drinks, demonstrating a general&#xD;
        motivational effect. In contrast, during outcome-specific PIT, this effect is limited for the&#xD;
        same stimulus-reward association. For instance, Pavlovian stimuli associated with a soft&#xD;
        drink promote choices for the same soft drink outcome only.&#xD;
  &#xD;
        Methods:&#xD;
  &#xD;
        Between-group Analysis: The investigators will assess the outcome-specific PIT effects by&#xD;
        measuring the change in the proportion of alcohol choices when the alcohol cue is presented&#xD;
        versus when the soft drink (juice) cue is shown. On the other hand, the investigators will&#xD;
        define general PIT effects as the increase in button presses (i.e., slope) corresponding to&#xD;
        the increased valence of the conditioned monetary cues. The investigators plan to examine the&#xD;
        differences in both specific and general PIT effects at both the behavioral and neural levels&#xD;
        between the AUD group and the non-AUD group, controlling for smoking status. Additionally,&#xD;
        the investigators will investigate the relationship between specific and general PIT effects&#xD;
        and AUDIT, along with quantity-frequency measures Comparison between the two PIT tasks: the&#xD;
        investigators will explore similarities and differences in PIT effects between the full PIT&#xD;
        paradigm and the previously-mentioned single-lever PIT paradigm.&#xD;
  &#xD;
        Stress: the investigators will test whether levels of chronic stress (assessed with&#xD;
        questionnaires and hair cortisol as for Experiment 1) moderate outcome-specific and full PIT&#xD;
        effects.&#xD;
  &#xD;
        Hypothesis 3a:&#xD;
  &#xD;
        The investigators expect that both outcome-specific and general PIT effects will be stronger&#xD;
        in participants with AUD compared to those without AUD, evident at both behavioral and neural&#xD;
        levels. Additionally, the investigators predict positive associations between PIT effects and&#xD;
        both AUDIT scores and quantity-frequency measures.&#xD;
  &#xD;
        Hypothesis 3b:&#xD;
  &#xD;
        the investigators hypothesize that the PIT effect found in the single-lever PIT task is more&#xD;
        strongly associated with the general PIT and less strongly associated with the&#xD;
        outcome-specific PIT effect in the full PIT task.&#xD;
  &#xD;
        Hypothesis 3c:&#xD;
  &#xD;
        Increased chronic stress will enhance effects of both general and outcome-specific PIT.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">November 24, 2020</start_date>
    <completion_date type="Anticipated">December 31, 2023</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Case-Control</observational_model>
      <time_perspective>Retrospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Neural PIT effect day 1</measure>
      <time_frame>Day 1</time_frame>
      <description>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</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Neural PIT effect day 2</measure>
      <time_frame>Day 2</time_frame>
      <description>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</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Behavioral PIT effect on performance day 1</measure>
      <time_frame>Day 1</time_frame>
      <description>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.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Behavioral PIT effect on velocity day 1</measure>
      <time_frame>Day 1</time_frame>
      <description>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.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Behavioral PIT effect on velocity day 2</measure>
      <time_frame>Day 2</time_frame>
      <description>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.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Chronic stress effects on hair cortisol in picogram/milligram</measure>
      <time_frame>retrospective assessment before PIT testing at Day 1</time_frame>
      <description>chronic stress assessment via:&#xD;
  - hair cortisol measurement (3 cm hair segments)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Chronic stress quenstionnaire 1</measure>
      <time_frame>retrospective assessment before PIT testing at Day 1</time_frame>
      <description>chronic stress assessment via:&#xD;
  - 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))</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Chronic stress quenstionnaire 2</measure>
      <time_frame>retrospective assessment before PIT testing at Day 1</time_frame>
      <description>chronic stress assessment via:&#xD;
  - 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)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Chronic stress quenstionnaire 3</measure>
      <time_frame>retrospective assessment before PIT testing at Day 1</time_frame>
      <description>chronic stress assessment via:&#xD;
  - 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)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>cognitive control Stroop effect</measure>
      <time_frame>Day 1</time_frame>
      <description>Cognitive control assessment via:&#xD;
  - Counting Stroop task</description>
    </primary_outcome>
    <primary_outcome>
      <measure>cognitive control Simon effect</measure>
      <time_frame>Day 1</time_frame>
      <description>Cognitive control assessment via:&#xD;
  No-go Simon task</description>
    </primary_outcome>
    <primary_outcome>
      <measure>cognitive control interference effect</measure>
      <time_frame>Day 1</time_frame>
      <description>Cognitive control assessment via:&#xD;
  Stop Signal reaction time task</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Acute stress day 1</measure>
      <time_frame>Day 1</time_frame>
      <description>Acute stress inducting using:&#xD;
  Trier social stress test (TSST) OR placebo (randomized across days between subjects)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Acute stress day 2</measure>
      <time_frame>Day 2</time_frame>
      <description>Acute stress inducting using:&#xD;
  Trier social stress test (TSST) OR placebo (randomized across days between subjects)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Saliva cortisol concentration in nmol/litre</measure>
      <time_frame>Assessment before, during and after TSST (-60 minutes, 0 minutes, +10 minutes, +20 minutes, +30 minutes,+ 50 minutes, +80 minutes)</time_frame>
      <description>Acute stress effects in AUD and HC</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>alcohol consumption after 12 months</measure>
      <time_frame>12 months after testing for behavioral and neural PIT effects</time_frame>
      <description>alcohol drinking amount (quantity, frequency) during a follow-up period of 12 months</description>
    </secondary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">300</enrollment>
    <condition>Alcohol Use Disorder (AUD)</condition>
    <condition>Alcoholism</condition>
    <condition>Substance Use Disorders</condition>
    <condition>Smoking, Tobacco</condition>
    <condition>Stress Reaction</condition>
    <condition>Stress</condition>
    <arm_group>
      <arm_group_label>alcohol use disorder (AUD)</arm_group_label>
      <description>Participants with alcohol use disorder (mild to moderate or severe if no withdrawal symptoms) including:&#xD;
  daily smokers (at least 1 cigarette per day in last 3 months)&#xD;
  non-daily (min 1x/last 3months)&#xD;
  non-smokers</description>
    </arm_group>
    <arm_group>
      <arm_group_label>non-AUD</arm_group_label>
      <description>Participants with a maximum of 1 AUD criteria according to DSM-5, including:&#xD;
  daily smokers (at least 1 cigarette per day in last 3 months)&#xD;
  non-daily (min 1x/last 3months)&#xD;
  non-smokers</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>fMRI imaging (BOLD)</intervention_name>
      <description>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.</description>
      <arm_group_label>alcohol use disorder (AUD)</arm_group_label>
      <arm_group_label>non-AUD</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>sMRI (structure)</intervention_name>
      <description>Will be used to investigate neural correlates of PIT effects by identifying abnormalities in cortical gray and white matter volume.</description>
      <arm_group_label>alcohol use disorder (AUD)</arm_group_label>
      <arm_group_label>non-AUD</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Trier Social Stress Test</intervention_name>
      <description>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.</description>
      <arm_group_label>alcohol use disorder (AUD)</arm_group_label>
      <arm_group_label>non-AUD</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>PIT paradigm</intervention_name>
      <description>The paradigm consists of four parts:&#xD;
  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.</description>
      <arm_group_label>alcohol use disorder (AUD)</arm_group_label>
      <arm_group_label>non-AUD</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Counting Stroop task</intervention_name>
      <description>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</description>
      <arm_group_label>alcohol use disorder (AUD)</arm_group_label>
      <arm_group_label>non-AUD</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>No-go Simon task</intervention_name>
      <description>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.</description>
      <arm_group_label>alcohol use disorder (AUD)</arm_group_label>
      <arm_group_label>non-AUD</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Stop Signal Task</intervention_name>
      <description>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 &quot;stop trials&quot; one of the fruits turns brown (rotten), indicating the corresponding side of the screen should not be tapped.</description>
      <arm_group_label>alcohol use disorder (AUD)</arm_group_label>
      <arm_group_label>non-AUD</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>blood samples</intervention_name>
      <description>for genetic and epigenetic testing, especially for exploratory outcome prediction using polygenic risk scores.</description>
      <arm_group_label>alcohol use disorder (AUD)</arm_group_label>
      <arm_group_label>non-AUD</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>questionnaires for chronic stress</intervention_name>
      <description>Perceived Stress Scale&#xD;
  Social Readjustment Rating Scale&#xD;
  Trier Inventory for the Assessment of Chronic</description>
      <arm_group_label>alcohol use disorder (AUD)</arm_group_label>
      <arm_group_label>non-AUD</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>hair samples</intervention_name>
      <description>Hair cortisol measurement (3 cm hair segments) will be used to assess chronic stress.</description>
      <arm_group_label>alcohol use disorder (AUD)</arm_group_label>
      <arm_group_label>non-AUD</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>saliva samples</intervention_name>
      <description>Assessing acute stress effects in AUD.</description>
      <arm_group_label>alcohol use disorder (AUD)</arm_group_label>
      <arm_group_label>non-AUD</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>EMA assessment</intervention_name>
      <description>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).</description>
      <arm_group_label>alcohol use disorder (AUD)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>clinical diagnostic</intervention_name>
      <description>SKID-I Interview neurocognitive and psychopathological testing</description>
      <arm_group_label>alcohol use disorder (AUD)</arm_group_label>
      <arm_group_label>non-AUD</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          All groups will be recruited from general population via advertisement (e.g. ebay&#xD;
          Kleinanzeigen, Facebook) and notes (e.g. blackbords, intranet) in Berlin and Dresden&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  males and females between 16-65 years of age&#xD;
  &#xD;
            -  AUD subjects only: meet a minimum of 2 criteria for DSM-5 alcohol-related disorder&#xD;
               (AUD) (not requiring withdrawal as assessed by an independent psychiatrist) and AUDIT&#xD;
               &gt; 4&#xD;
  &#xD;
            -  Smokers: Daily smokers only: smoke 7 days/week during the last three months&#xD;
  &#xD;
            -  Non-daily smokers only: smoke at least once but less than 7 days/week during the last&#xD;
               three months&#xD;
  &#xD;
            -  Ability to consent to the study and complete the questionnaires&#xD;
  &#xD;
            -  Sufficient language skills: German&#xD;
  &#xD;
            -  Availability between 3pm-6pm on 2 consecutive days (Experiment 1, acute stress&#xD;
               question)&#xD;
  &#xD;
            -  Females only: luteal phase (Experiment 1, acute stress question)&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Lifetime diagnosis according to DMS-5 for: Bipolar disorder, schizophrenia,&#xD;
               schizophrenia spectrum disorder, substance dependence except for alcohol, nicotine, or&#xD;
               cannabis&#xD;
  &#xD;
            -  Currently meeting DSM-5 diagnostic criteria for a depressive episode, suicidal&#xD;
               ideation&#xD;
  &#xD;
            -  Past traumatic brain injury or severe neurological disease (such as dementia,&#xD;
               Parkinson's disease, multiple sclerosis)&#xD;
  &#xD;
            -  Pregnancy or breastfeeding&#xD;
  &#xD;
            -  Ingestion of medications known to interact with the CNS in the 10-day period prior to&#xD;
               study participation or less than 4 half-lives after last ingestion (rapid urine test)&#xD;
  &#xD;
            -  MR contraindications (e.g., pacemakers, metallic or electronic implants, metallic&#xD;
               splinters, surgical staples)&#xD;
  &#xD;
            -  Color vision deficiency&#xD;
  &#xD;
            -  Sensorineural hearing loss of 30 dB or greater,&#xD;
  &#xD;
            -  Tinnitus&#xD;
  &#xD;
            -  Presence of claustrophobia&#xD;
  &#xD;
            -  Acute alcohol intoxication at MRI appointments verified by breath alcohol testing or&#xD;
               drug intoxication verified by rapid urine testing&#xD;
  &#xD;
            -  For women only: not peri- or postmenopausal, not taking contraceptives (Experiment 1,&#xD;
               acute stress question)&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>16 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
    </eligibility>
    <overall_contact>
      <last_name>Andreas Heinz, Prof., MD, PhD</last_name>
      <phone>0049 30 450 517 001</phone>
      <email>andreas.heinz@charite.de</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Maximilian Pilhatsch, MD, PhD</last_name>
      <phone>0049 (351) 458 19312</phone>
      <email>max.pilhatsch@uniklinikum-dresden.de</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Charite - Universitätsmedizin Berlin</name>
        <address>
          <city>Berlin</city>
          <zip>10117</zip>
          <country>Germany</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Andreas Heinz, Prof., MD, PhD</last_name>
        <phone>004930450517002</phone>
        <email>andreas.heinz@charite.de</email>
      </contact>
      <investigator>
        <last_name>Andreas Heinz, Prof., MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Maximilian Pilhatsch, PD.; MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Michael N Smolka, Prof., MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Technische Universität Dresden</name>
        <address>
          <city>Dresden</city>
          <zip>01307</zip>
          <country>Germany</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Maximilian Pilhatsch, Prof., MD, PhD</last_name>
        <phone>0049 (351) 458 19312</phone>
        <email>max.pilhatsch@uniklinikum-dresden.de</email>
      </contact>
    </location>
    <location_countries>
      <country>Germany</country>
    </location_countries>
    <results_reference>
      <citation>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.</citation>
      <PMID>36380640</PMID>
    </results_reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>June 30, 2023</study_first_submitted>
    <study_first_submitted_qc>August 7, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 15, 2023</study_first_posted>
    <last_update_submitted>August 7, 2023</last_update_submitted>
    <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Charite University, Berlin, Germany</investigator_affiliation>
      <investigator_full_name>Andreas Heinz</investigator_full_name>
      <investigator_title>head of Department of Psychiatry and Psychotherapy | CCM, principle investigator</investigator_title>
    </responsible_party>
    <keyword>substance use disorder (SUD), cognitive control/interference</keyword>
    <keyword>alcohol use disorder (AUD)</keyword>
    <keyword>Smokers</keyword>
    <keyword>general and outcome-specific Pavlovian to instrumental transfer</keyword>
    <keyword>chronic and acute stress</keyword>
    <keyword>Amygdala</keyword>
    <keyword>Stroop Test</keyword>
    <keyword>Ventral Striatum</keyword>
    <keyword>Neuroimaging</keyword>
    <keyword>Humans</keyword>
    <keyword>Surveys and Questionnaires</keyword>
    <keyword>Reward</keyword>
    <keyword>Fractals</keyword>
    <keyword>Cues</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Substance-Related Disorders</mesh_term>
      <mesh_term>Alcoholism</mesh_term>
      <mesh_term>Fractures, Stress</mesh_term>
      <mesh_term>Alcohol Drinking</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05992272
  org study id: 402170461
  nct id: NCT05992272
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  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.
  This project has four research aims:
  
          1. The investigators want to assess the effects of acute as well as repeated stress
             exposure on PIT and its neuroimaging correlates, and the investigators will test whether
             modulation of PIT by stress predicts losing vs. regaining control of drug intake in mild
             to moderate AUD subjects.
  
          2. The investigators will investigate how cognitive control abilities (e.g. interference
             control and response inhibition) are related to the costs of interference between
             Pavlovian and instrumental control in PIT.
  
          3. The investigators will compare PIT, its relation to cognitive control, and the neural
             mechanisms between different drugs of abuse by investigating participants with AUD and
             also smokers.
  
          4. The investigators will develop an outcome-specific PIT paradigm with alternative (food)
             and drug rewards to compare AUD and healthy controls, and the investigators will explore
             communalities and differences in behavioral and neural processes between general PIT and
             outcome-specific PIT.
  
        Therefore, the investigators conduct 3 Experiments with the following Hypotheses:
  
        Experiment 1:
  
        Here the investigators assess on a behavioral and neural level a general PIT task that
        consists of four parts:
  
        In the instrumental part, participants have to learn which shells to collect or leave in
        order to gain as much money as possible; the correct choice is probabilistically rewarded in
        80% of all times. Absolutely unrelated to this instrumental part, during Pavlovian
        conditioning colorful fractals are presented in the back of the screen, which have been
        passively paired either with monetary gain, no change or monetary loss, i.e. they act as
        positively valued, neutral or negatively valued cues. These fractals thus act as independent,
        Pavlovian conditioned background stimuli and interact with instrumental behavior in the
        unrelated third transfer part of the PIT task. Also, the investigators assess the effects of
        drug-specific cues in the background on instrumental behavior during this transfer part. To
        avoid further learning, the transfer part will be conducted under nominal extinction.
        Finally, query trials, in which participants will have to choose one of two pictures will to
        assess the relative cue value.
  
        Acute stress will be induced by the Trier Social Stress Test (TSST), chronic stress will be
        assessed by questionnaires and hair cortisol.
  
        Hypothesis 1a:
  
        Acute and chronic stress exposure increase behavioral and neural PIT effects elicited by
        monetary Pavlovian conditioned stimuli (CS) and decrease inhibitory effects of alcohol
        Pavlovian CS. Functional correlates of PIT effects will be found in the amygdala and in the
        ventral striatum.
  
        Hypothesis 1b:
  
        Following stress exposure, high PIT effects elicited by monetary Pavlovian CS and low
        inhibitory effects elicited by alcohol Pavlovian CS predict higher subsequent alcohol intake
        in the follow-up period of 6 months.
  
        Methods:
  
        Between group analysis: The investigators will analyze on a behavioral and imaging level how
        acutely consuming AUD subjects and matched controls differ regarding money- and
        alcohol-related PIT.
  
        Within-group analysis: The investigators will analyze how acute stress affects PIT effects.
        This 2x2 design (1 within-group subject factor with two levels: STRESS vs. NO STRESS and 1
        between-group subject factor with two levels: AUD vs. matched controls) will be tested on a
        behavioral and neural level.
  
        Experiment 2:
  
        In this experiment, the investigators will utilize a 2x3 factorial group design. Participants
        will be categorized into two main groups: those with AUD and those without (non-AUD). Each of
        these groups will be further divided into three subgroups: daily smokers, non-daily smokers
        and non-smokers. Each cell (individual subgroup) will consist of 35 subjects. In addition to
        the PIT task described above, the N = 210 participants will additionally perform a Counting
        Stroop task and a No-go Simon task. Participants will also perform a stop signal task during
        functional MRI (fMRI).
  
        Methods:
  
        Interference Costs: Interference costs will be calculated based on error rate (ER) and
        reaction time (RT) differences between task conditions, e.g., incongruent vs. congruent
        conditions.
  
        Between-group analysis: the investigators will examine group differences in the interference
        PIT effect at both the behavioral and neural levels using a two (AUD vs. non-AUD) by three
        (daily smokers vs. non-daily smokers vs. non-smokers) design. In addition, the investigators
        aim to investigate the associations between the interference PIT effect and other continuous
        measures: Alcohol Use Disorders Identification Test (AUDIT), Fagerström Test for Nicotine
        Dependence (FTND), along with quantity-frequency indices.
  
        Other analysis: In order to gain a better understanding of the mechanisms underlying PIT, the
        investigators will also fit a drift diffusion model to the behavioral data and explore the
        connectivity within the neural networks during PIT in relation to the connectivity during the
        stop signal task (response inhibition).
  
        Hypothesis 2a:
  
        Interference costs (i.e. increased error rate [ER] in instrumental responses) during PIT are
        associated with interference costs at the stimulus level (Stroop task) and at the response
        level (No-go Simon task), and these costs will also be correlated with the ER during response
        inhibition (No-go Simon task).
  
        Hypothesis 2b:
  
        The investigators hypothesize that the interference PIT effect will be more pronounced in the
        AUD group compared to the non-AUD group. The investigators also anticipate that the effect
        will be stronger in the smoker group. Furthermore, the investigators hypothesize a positive
        correlation between the PIT effect and AUDIT, FTND scores, as well as the quantity and
        frequency of use. As the behavioral PIT effect intensifies, the investigators expect
        corresponding neural responses to similarly increase.
  
        Experiment 3:
  
        The investigators here use a newly-developed full PIT paradigm that introduces primary
        reinforcers, i.e. alcoholic and soft drinks (that the investigators administer on a
        trial-by-trial basis). Furthermore, the investigators implemented additional Pavlovian
        stimuli to examine both general and outcome-specific PIT effects. General PIT effects occur
        when positively valued environmental Pavlovian stimuli enhance instrumental responding
        regardless of the reinforcer being used. Here, stimuli that are associated with e.g. monetary
        rewards can enhance instrumental responding for alcohol drinks, demonstrating a general
        motivational effect. In contrast, during outcome-specific PIT, this effect is limited for the
        same stimulus-reward association. For instance, Pavlovian stimuli associated with a soft
        drink promote choices for the same soft drink outcome only.
  
        Methods:
  
        Between-group Analysis: The investigators will assess the outcome-specific PIT effects by
        measuring the change in the proportion of alcohol choices when the alcohol cue is presented
        versus when the soft drink (juice) cue is shown. On the other hand, the investigators will
        define general PIT effects as the increase in button presses (i.e., slope) corresponding to
        the increased valence of the conditioned monetary cues. The investigators plan to examine the
        differences in both specific and general PIT effects at both the behavioral and neural levels
        between the AUD group and the non-AUD group, controlling for smoking status. Additionally,
        the investigators will investigate the relationship between specific and general PIT effects
        and AUDIT, along with quantity-frequency measures Comparison between the two PIT tasks: the
        investigators will explore similarities and differences in PIT effects between the full PIT
        paradigm and the previously-mentioned single-lever PIT paradigm.
  
        Stress: the investigators will test whether levels of chronic stress (assessed with
        questionnaires and hair cortisol as for Experiment 1) moderate outcome-specific and full PIT
        effects.
  
        Hypothesis 3a:
  
        The investigators expect that both outcome-specific and general PIT effects will be stronger
        in participants with AUD compared to those without AUD, evident at both behavioral and neural
        levels. Additionally, the investigators predict positive associations between PIT effects and
        both AUDIT scores and quantity-frequency measures.
  
        Hypothesis 3b:
  
        the investigators hypothesize that the PIT effect found in the single-lever PIT task is more
        strongly associated with the general PIT and less strongly associated with the
        outcome-specific PIT effect in the full PIT task.
  
        Hypothesis 3c:
  
        Increased chronic stress will enhance effects of both general and outcome-specific PIT.
  observational model: Case-Control
  time perspective: Retrospective
  measure: Neural PIT effect day 1
  time frame: Day 1
  description: 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
  measure: Neural PIT effect day 2
  time frame: Day 2
  description: 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
  measure: Behavioral PIT effect on performance day 1
  time frame: Day 1
  description: 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.
  measure: Behavioral PIT effect on velocity day 1
  time frame: Day 1
  description: 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.
  measure: Behavioral PIT effect on velocity day 2
  time frame: Day 2
  description: 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.
  measure: Chronic stress effects on hair cortisol in picogram/milligram
  time frame: retrospective assessment before PIT testing at Day 1
  description: chronic stress assessment via:
  - hair cortisol measurement (3 cm hair segments)
  measure: Chronic stress quenstionnaire 1
  time frame: retrospective assessment before PIT testing at Day 1
  description: 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))
  measure: Chronic stress quenstionnaire 2
  time frame: retrospective assessment before PIT testing at Day 1
  description: 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)
  measure: Chronic stress quenstionnaire 3
  time frame: retrospective assessment before PIT testing at Day 1
  description: 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)
  measure: cognitive control Stroop effect
  time frame: Day 1
  description: Cognitive control assessment via:
  - Counting Stroop task
  measure: cognitive control Simon effect
  time frame: Day 1
  description: Cognitive control assessment via:
  No-go Simon task
  measure: cognitive control interference effect
  time frame: Day 1
  description: Cognitive control assessment via:
  Stop Signal reaction time task
  measure: Acute stress day 1
  time frame: Day 1
  description: Acute stress inducting using:
  Trier social stress test (TSST) OR placebo (randomized across days between subjects)
  measure: Acute stress day 2
  time frame: Day 2
  description: Acute stress inducting using:
  Trier social stress test (TSST) OR placebo (randomized across days between subjects)
  measure: Saliva cortisol concentration in nmol/litre
  time frame: Assessment before, during and after TSST (-60 minutes, 0 minutes, +10 minutes, +20 minutes, +30 minutes,+ 50 minutes, +80 minutes)
  description: Acute stress effects in AUD and HC
  measure: alcohol consumption after 12 months
  time frame: 12 months after testing for behavioral and neural PIT effects
  description: alcohol drinking amount (quantity, frequency) during a follow-up period of 12 months
  arm group label: alcohol use disorder (AUD)
  description: 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
  arm group label: non-AUD
  description: 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
  intervention type: Biological
  intervention name: fMRI imaging (BOLD)
  description: 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.
  arm group label: alcohol use disorder (AUD)
  arm group label: non-AUD
  intervention type: Biological
  intervention name: sMRI (structure)
  description: Will be used to investigate neural correlates of PIT effects by identifying abnormalities in cortical gray and white matter volume.
  arm group label: alcohol use disorder (AUD)
  arm group label: non-AUD
  intervention type: Behavioral
  intervention name: Trier Social Stress Test
  description: 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.
  arm group label: alcohol use disorder (AUD)
  arm group label: non-AUD
  intervention type: Behavioral
  intervention name: PIT paradigm
  description: 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.
  arm group label: alcohol use disorder (AUD)
  arm group label: non-AUD
  intervention type: Behavioral
  intervention name: Counting Stroop task
  description: 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
  arm group label: alcohol use disorder (AUD)
  arm group label: non-AUD
  intervention type: Behavioral
  intervention name: No-go Simon task
  description: 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.
  arm group label: alcohol use disorder (AUD)
  arm group label: non-AUD
  intervention type: Diagnostic Test
  intervention name: Stop Signal Task
  description: 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.
  arm group label: alcohol use disorder (AUD)
  arm group label: non-AUD
  intervention type: Diagnostic Test
  intervention name: blood samples
  description: for genetic and epigenetic testing, especially for exploratory outcome prediction using polygenic risk scores.
  arm group label: alcohol use disorder (AUD)
  arm group label: non-AUD
  intervention type: Diagnostic Test
  intervention name: questionnaires for chronic stress
  description: Perceived Stress Scale
  Social Readjustment Rating Scale
  Trier Inventory for the Assessment of Chronic
  arm group label: alcohol use disorder (AUD)
  arm group label: non-AUD
  intervention type: Diagnostic Test
  intervention name: hair samples
  description: Hair cortisol measurement (3 cm hair segments) will be used to assess chronic stress.
  arm group label: alcohol use disorder (AUD)
  arm group label: non-AUD
  intervention type: Diagnostic Test
  intervention name: saliva samples
  description: Assessing acute stress effects in AUD.
  arm group label: alcohol use disorder (AUD)
  arm group label: non-AUD
  intervention type: Diagnostic Test
  intervention name: EMA assessment
  description: 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).
  arm group label: alcohol use disorder (AUD)
  intervention type: Diagnostic Test
  intervention name: clinical diagnostic
  description: SKID-I Interview neurocognitive and psychopathological testing
  arm group label: alcohol use disorder (AUD)
  arm group label: non-AUD
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 16 Years
  maximum age: 65 Years
  last name: Andreas Heinz, Prof., MD, PhD
  phone: 0049 30 450 517 001
  email: andreas.heinz@charite.de
  last name: Maximilian Pilhatsch, MD, PhD
  phone: 0049 (351) 458 19312
  email: max.pilhatsch@uniklinikum-dresden.de
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  investigator: 
  investigator: 
  facility: 
  status: Recruiting
  contact: 
  country: Germany
  citation: 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
  responsible party type: Principal Investigator
  investigator affiliation: Charite University, Berlin, Germany
  investigator full name: Andreas Heinz
  investigator title: head of Department of Psychiatry and Psychotherapy | CCM, principle investigator
  mesh term: Substance-Related Disorders
  mesh term: Alcoholism
  mesh term: Fractures, Stress
  mesh term: Alcohol Drinking