The Role of Dopaminergic and Glutamatergic Neurotransmission for Dysfunctional Learning in Alcohol Use Disorders

NCT ID: NCT02094196

Last Updated: 2020-07-30

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2018-12-31

Brief Summary

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).

Detailed Description

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.

Conditions

Alcohol Use Disorder

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Controls, highrisk for AD

Community-based ad-hoc participants, high risk for alcohol dependence, matched to inpatients by sociodemographics

No interventions assigned to this group

Controls, low risk for AD

Community-based ad-hoc participants, low risk for alcohol dependence, matched to inpatients by sociodemographics

No interventions assigned to this group

Alcohol detoxification

Inpatients with alcohol dependence from local psychiatric hospital wards (18-65 years old)

Alcohol detoxification

Intervention Type: OTHER

Detoxified alcohol- dependent patients in an inpatient setting

Interventions

Alcohol detoxification

Detoxified alcohol- dependent patients in an inpatient setting

Intervention Type: OTHER

Other Intervention Names

Alcohol- dependent patients

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Charite University, Berlin, Germany

OTHER

Sponsor Role: collaborator

Technische Universität Dresden

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jürgen Gallinat, Prof MD

Role: PRINCIPAL_INVESTIGATOR

Charite University, Berlin, Germany

Andreas Heinz, Prof MD

Role: STUDY_CHAIR

Charite University, Berlin, Germany

Hans-Ulrich Wittchen, Prof PhD

Role: STUDY_DIRECTOR

Technische Universität Dresden, Dresden, Germany

Locations

Charité Berlin, Division of Neuroimaging

Berlin, , Germany

Charité - Universitätsmedizin Berlin

Berlin, , Germany

Countries

Germany

References

Spitta G, Gleich T, Maricic LM, Rosenthal A, Schubert F, Aydin S, Heinz A, Gallinat J. Reduced GABA Levels in the ACC of Actively Drinking High Risk Individuals Compared to Recently Detoxified Alcohol-Dependent Patients. J Integr Neurosci. 2024 Oct 14;23(10):190. doi: 10.31083/j.jin2310190.

Reference Type: DERIVED

PMID: 39473159 (View on PubMed)

Related Links

http://gepris.dfg.de/gepris/projekt/209293518

English study description

Other Identifiers

GA707/6-1

Identifier Type: -

Identifier Source: org_study_id