An integrated approach to identify neurobiological mechanisms of addictive behaviour

Addiction disorders are frequent oligogenic disorder with complex inheritance patterns and interplay of genetic and environmental factors contributing to their phenotype. They are heterogenous by nature with common and distinct genes contributing to different phenotypes of substance use disorders. To identify the genetic and neurobiological basis of addiction disorders we take into account these characteristics by identifying candidate genes shown to alter drug taking behaviour in animal models and analyse them for association with analogous phenotypes of substance use disorders in humans. A recent example of this approach, the characterization of the role of a circadian rhythm gene Period 2 in human alcohol drinking behaviour will be presented (Nature Medicine, 2005; 11: 35-42). Neuroimaging permits reduction in phenotypic heterogeneity by measuring specific brain functions implicated in the etiology of addiction disorders and link them to genetic variations and behavioural characteristics relevant to disease processes. We will provide examples demonstrating the validity of this approach by analyzing the association of 5-HTT and COMT genotypes with fMRI-response to negative emotional cues (Nature Neuroscience, 2005; 8: 20-21, J. Neuroscience, 2005; 25: 836-42, Mol. Psychiatry 2007, 12:307-17 ). The integration of our candidate gene approach using behavioural animal models and neuroimaging studies will be described by providing an outlook of a recently funded EU-integrated gene-neuroimaging project “IMAGEN”.