Endophenotyping With fMRI: Genetic Modulation and Treatment Response

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.