Cue Effects in Human Addiction: Pavlovian to Instrumental Transfer
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 300
- 试验地点
- 2
- 主要终点
- cognitive control Stroop effect
研究概览
简要总结
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.
详细描述
This project has four research aims:
- 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.
- 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.
- 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.
- 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:
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 16 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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,
- •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)
结局指标
主要结局
cognitive control Stroop effect
时间窗: Day 1
Cognitive control assessment via: - Counting Stroop task
cognitive control interference effect
时间窗: Day 1
Cognitive control assessment via: Stop Signal reaction time task
Behavioral PIT effect on velocity day 1
时间窗: 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.
Chronic stress quenstionnaire 2
时间窗: retrospective assessment before PIT testing at Day 1
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)
Chronic stress quenstionnaire 3
时间窗: retrospective assessment before PIT testing at Day 1
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)
cognitive control Simon effect
时间窗: Day 1
Cognitive control assessment via: No-go Simon task
Neural PIT effect day 1
时间窗: 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
Behavioral PIT effect on performance day 1
时间窗: 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.
Chronic stress effects on hair cortisol in picogram/milligram
时间窗: retrospective assessment before PIT testing at Day 1
chronic stress assessment via: - hair cortisol measurement (3 cm hair segments)
Neural PIT effect day 2
时间窗: 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 velocity day 2
时间窗: 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.
Chronic stress quenstionnaire 1
时间窗: retrospective assessment before PIT testing at Day 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))
Acute stress day 1
时间窗: Day 1
Acute stress inducting using: Trier social stress test (TSST) OR placebo (randomized across days between subjects)
Acute stress day 2
时间窗: Day 2
Acute stress inducting using: Trier social stress test (TSST) OR placebo (randomized across days between subjects)
次要结局
- 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)
研究者
Andreas Heinz
head of Department of Psychiatry and Psychotherapy | CCM, principle investigator
Charite University, Berlin, Germany