Learning and Relapse Risk in Alcohol Dependence

Study Overview
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Brief Summary
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The aim of this project is to assess which behavioral and neuroimaging alterations associated with reward- based learning predict relapse in alcohol- dependent patients within a follow- up period of 12 months. The investigators will explore how these alterations interact with clinical and psychosocial factors which can modify the relapse risk. Functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) will be used to identify neurofunctional abnormalities in neurotransmitter systems. The investigators will also provide data for genetic analysis and modeling. Patients will be detoxified in an inpatient setting and followed for 12 months using the Time-Line Follow- Back Procedure. 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.

Detailed Description
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This project will examine 150 detoxified alcohol-dependent patients and 100 age- and gender matched controls. The main aim of this project is to assess 1) which behavioural and neuroimaging alterations (fMRI) associated with reward-based learning (see Projects 1 & 3) predict relapse within the follow-up period of 6 months, 2) how these interact with clinical and psychosocial factors which can modify the relapse risk, and 3) to provide data for genetic and imaging analyses and modelling. Furthermore, we will explore gender effects on functional imaging parameters of learning. Patients will be detoxified in an inpatient setting and followed for 6 months using the Form 90 and Time-Line Follow-Back Procedure. Clinical assessments, behavioral paradigms of learning, and brain imaging will be carried out within at least 4 half-lives after any psychotropic medication. Subjects will undergo medical management with bimonthly follow-ups and predefined in- and exclusion criteria as described previously. We will implement and apply functional imaging paradigms assessing Pavlovian-to-instrumental transfer and reversal learning as described in Projects 1 and 3. We will associate model parameters of learning with alcohol craving, intake and prospective relapse risk. Independent of these central questions, we will also assess comorbidity, psychosocial and neurobiological disease severity markers to control for specificity of findings.

Official Title
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Learning Mechanisms as Predictors of Treatment Outcome in Alcohol- Dependent Patients

Conditions
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Alcohol Use Disorders

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Alcohol- dependent patients<br>Detoxified alcohol- dependent patients in an inpatient setting | |
| Control group<br>Age- and gender matched healthy controls | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| blood oxygenation level dependent (BOLD) response | investigation of neuronal activation of the mesolimbic system in alcohol-dependent patients and healthy controls using 3 Tesla magnetic resonance imaging | first assessment time point (alc. dependent pat. up to 21 days after detoxification) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment response | test the predictive effects of learning parameters and related neuronal correlates for treatment outcome (relapse vs abstinence) in alcohol-dependent patients | 12-month follow-up period beginning after first assessment timepoint | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Reward- based learning, Pavlovian-to-instrumental transfer, Functional imaging, Relapse risk