Endophenotyping With Functional Magnetic Resonance Imaging (fMRI)
Condition: Alcohol Dependence
MeSH terms: Alcoholism
Study type: Observational

Summary: 
      The mesolimbic dopaminergic reward system is a key structure underlying addictive behaviour
      in alcohol addiction and is under control of prefrontal glutamatergic neurotransmission. The
      aim of the present multicenter-study in Berlin, Bonn and Mannheim is to use functional
      magnetic resonance imaging (fMRI) in alcohol addiction for endophenotyping in order to study
      the relevance of genetic variation, in particular in dopaminergic and glutamatergic genes,
      for addiction. The investigators will use a temporal discounting and a cue reactivity
      paradigm in alcoholics and healthy controls in order to 1) test the impact of genetic
      variation on activation of the mesolimbic system in these populations and to 2) to test their
      predictive effects for treatment outcome in alcoholics. The subproject will thus bridge
      animal research on genetically determined cue reactivity and human studies in alcoholics.
      Furthermore, the investigators will link these results to the measurement of glutamate and
      glutamine with magnetic resonance spectroscopy (MRS) in subproject SP14.
    

Detailed description: 
      Alcohol addiction is one of the most common neuropsychiatric diseases in today's society.
      Chronic misuse of alcohol not only causes significant physical and psychological damage in
      afflicted individuals, it also represents a serious social and economic problem. Despite the
      availability of a range of psychological and medical therapies, the risk of relapse for
      dependent individuals remains high even after years of abstinence. New, more effective
      therapies are urgently needed. Approximately 50% of the predisposition to develop an alcohol
      addiction is genetically inherited. In order to create improved treatment approaches and
      novel diagnostic tools, an enhanced knowledge of the genetic basis and biology of alcohol
      addiction is a prerequisite.

      The aim of this multi-centre study is to investigate how and which genetic variations
      increase the risk for developing an alcohol-addiction. To achieve this, scientists in Berlin,
      Bonn and Mannheim will examine specific brain mechanisms that play important roles in alcohol
      dependence. Functional Magnetic Resonance Imaging (fMRI), a technique that makes it possible
      to observe the brain 'at work', will be used to reveal brain mechanisms affected by alcohol
      addiction such as the processing of reward and punishment, behaviour control and memory. It
      will then be investigated which genes or gene-gene interactions underlie these neuronal
      mechanisms. This powerful approach has the potential to uncover 'addiction-pathways' through
      which genes affect personality, drinking behaviours and success in staying abstinent via
      their influences on neuronal mechanisms.

      A special emphasis of this project lies upon the so-called 'reward system', which processes
      naturally rewarding stimuli (e.g. food, sex) and which, in alcohol-dependent individuals,
      changes perceptions and behaviours in such a way that they become progressively more focused
      on alcohol. Two major neurotransmitters are involved in the workings of the reward system:
      'dopamine' and more indirectly 'glutamate'. The project will investigate how dopaminergic and
      glutamatergic genes influence the neural mechanisms of reward processing, other neural
      mechanisms, personality, drinking behaviours and therapy success. In the long run, this
      knowledge might lead to more effective therapies such as the development of new medications.

      This large-scale study will be conducted with several hundreds of alcohol-dependent patients
      and non-dependent individuals over a period of five years.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        primary care clinic
      
Biospecimen description: 
      whole blood (EDTA)
    
Keywords: alcohol dependence, functional magnetic resonance imaging, genetics, endophenotypes, dopamine,; glutamate