The Role of Dopaminergic and Glutamatergic Neurotransmission for Dysfunctional Learning in Alcohol Use Disorders (LeADP5)
The Role of Dopaminergic and Glutamatergic Neurotransmission for Dysfunctional Learning in Alcohol Use Disorders (LeAD P5)
The aim of this project is to assess reward- based learning behavior and its association with alterations in dopaminergic and glutamatergic transmission in detoxified alcohol-dependent patients and matched controls.
The investigators will explore how these alterations interact with clinical and psychosocial factors which can modify the relapse risk and learning deficits.
Patients will be detoxified in an inpatient setting. Clinical assessments, behavioral paradigms of learning and brain imaging will be carried out within at least 4 half- lives after any psychotropic medication.
The investigators will implement and apply functional imaging paradigms assessing Pavlovian-to-instrumental transfer and reversal learning tasks and associate model parameters of learning with alcohol craving, intake and prospective relapse risk.
In this project, the impact of the dopamine x glutamate interaction on learning deficits and consecutive relapse probability is targeted with [18F]fallypride PET and the measurement of absolute concentrations of glutamate with magnetic resonance spectroscopy (MRS).
研究概览
详细说明
Alcohol consumption despite negative consequences may rely on impaired flexibility in adapting the behavior to environmental changes, i.e. learning in response to reward contingencies. This learning deficit is of clinical relevance particularly during therapy and for the psychosocial outcome.
The reduced availability of central dopamine D2-receptors in detoxified alcohol dependent patients observed in PET investigations and their hypothetical effects on reward-related learning are in line with evidence for learning deficits in hypodopaminergic states, particularly for avoidance learning in non-dependent samples. Growing evidence indicates that the learning-related striatal dopamine signals are modulated by higher executive functions involving, e.g., the prefrontal cortex.
Here, broad glutamatergic outputs of the prefrontal cortex are crucial for subcortical learning mechanisms and match with recent models of interactive dopamine-glutamate dysfunctions and models of neurotrophic signaling in alcohol dependence.
研究类型
注册 (实际的)
联系人和位置
学习地点
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Berlin、德国、10117
- Charité - Universitätsmedizin Berlin
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Berlin、德国、10115
- Charité Berlin, Division of Neuroimaging
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
取样方法
研究人群
描述
Inclusion Criteria:
- Alcohol dependence according to DSM-IV
- Minimum of 72 hours of abstinence, maximum of 21 days of abstinence
- Minimum of three years of alcohol dependence
- Low severity of withdrawal symptoms
- Ability to provide fully informed consent and to use self- rating scales
Exclusion Criteria:
- Lifetime history of DSM- IV bipolar or psychotic disorder
- Current threshold DSM-IV diagnosis of any following disorders: current major - depressive disorder, generalized anxiety disorder, PTSD, borderline personality disorder or obsessive- compulsive disorder
- History of substance dependence other than alcohol or nicotine dependence
学习计划
研究是如何设计的？
设计细节
队列和干预
团体/队列 |
干预/治疗 |
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Controls, highrisk for AD
Community-based ad-hoc participants, high risk for alcohol dependence, matched to inpatients by sociodemographics
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Controls, low risk for AD
Community-based ad-hoc participants, low risk for alcohol dependence, matched to inpatients by sociodemographics
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Alcohol detoxification
Inpatients with alcohol dependence from local psychiatric hospital wards (18-65 years old)
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Detoxified alcohol- dependent patients in an inpatient setting
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Striatal D2-receptor availability (PET) and prefrontal glutamate concentration (MRS)
大体时间：first assessment time point (alc. dependent pat. up to 21 days after detoxification)
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reduction in striatal D2-receptor availability and a increase in prefrontal glutamate concentration in alcohol-dependent patients compared to healthy controls
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first assessment time point (alc. dependent pat. up to 21 days after detoxification)
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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behavioral data in reward-habit-learning paradigms
大体时间：first assessment time point (alc. dependent pat. up to 21 days after detoxification)
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Reduced learning speed and PIT withdrawal score in the probabilistic reversal learning task
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first assessment time point (alc. dependent pat. up to 21 days after detoxification)
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Treatment response
大体时间：12-month follow-up period beginning after first assessment timepoint
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test the predictive effects of striatal D2-receptor availability and prefrontal glutamate availability for treatment outcome (relapse vs abstinence) in alcohol-dependent patients
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12-month follow-up period beginning after first assessment timepoint
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其他结果措施
结果测量 |
措施说明 |
大体时间 |
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striatal-prefrontal connectivity (fMRI)
大体时间：first assessment time point (alc. dependent pat. up to 21 days after detoxification)
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striatal-prefrontal connectivity (see other LeAD-projects) in the probabilistic reversal learning task
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first assessment time point (alc. dependent pat. up to 21 days after detoxification)
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合作者和调查者
调查人员
- 首席研究员：Jürgen Gallinat, Prof MD、Charite University, Berlin, Germany
出版物和有用的链接
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
关键字
其他研究编号
- GA707/6-1
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
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