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).
調査の概要
詳細な説明
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.
研究の種類
入学 (実際)
連絡先と場所
研究場所
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Berlin、ドイツ、10117
- Charité - Universitätsmedizin Berlin
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Berlin、ドイツ、10115
- Charité Berlin, Division of Neuroimaging
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
コホートと介入
グループ/コホート |
介入・治療 |
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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
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Striatal D2-receptor availability (PET) and prefrontal glutamate concentration (MRS)
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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behavioral data in reward-habit-learning paradigms
時間枠：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
時間枠：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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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
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striatal-prefrontal connectivity (fMRI)
時間枠：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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協力者と研究者
捜査官
- 主任研究者：Jürgen Gallinat, Prof MD、Charite University, Berlin, Germany
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
その他の研究ID番号
- GA707/6-1
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
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