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).
Studieöversikt
Detaljerad beskrivning
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.
Studietyp
Inskrivning (Faktisk)
Kontakter och platser
Studieorter
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Berlin, Tyskland, 10117
- Charité - Universitätsmedizin Berlin
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Berlin, Tyskland, 10115
- Charité Berlin, Division of Neuroimaging
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Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Testmetod
Studera befolkning
Beskrivning
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
Studieplan
Hur är studien utformad?
Designdetaljer
Kohorter och interventioner
Grupp / Kohort |
Intervention / Behandling |
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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
Andra namn:
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Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
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Striatal D2-receptor availability (PET) and prefrontal glutamate concentration (MRS)
Tidsram: 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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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
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behavioral data in reward-habit-learning paradigms
Tidsram: 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
Tidsram: 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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Andra resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
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striatal-prefrontal connectivity (fMRI)
Tidsram: 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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Samarbetspartners och utredare
Sponsor
Samarbetspartners
Utredare
- Huvudutredare: Jürgen Gallinat, Prof MD, Charite University, Berlin, Germany
Publikationer och användbara länkar
Användbara länkar
Studieavstämningsdatum
Studera stora datum
Studiestart (Faktisk)
Primärt slutförande (Faktisk)
Avslutad studie (Faktisk)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Uppskatta)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- GA707/6-1
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
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