Alcohol Dependence Clinical Trial
Official title:
Endophenotyping With fMRI: Genetic Modulation and Treatment Response
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.
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.
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