The Role of Dopaminergic and Glutamatergic Neurotransmission for Dysfunctional Learning in Alcohol Use Disorders (LeAD P5)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Striatal D2-receptor availability (PET) and prefrontal glutamate concentration (MRS)
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Striatal D2-receptor availability (PET) and prefrontal glutamate concentration (MRS)
时间窗: first assessment time point (alc. dependent pat. up to 21 days after detoxification)
reduction in striatal D2-receptor availability and a increase in prefrontal glutamate concentration in alcohol-dependent patients compared to healthy controls
次要结局
- behavioral data in reward-habit-learning paradigms(first assessment time point (alc. dependent pat. up to 21 days after detoxification))
- Treatment response(12-month follow-up period beginning after first assessment timepoint)