Editorial

Analysis of biological mechanisms in addiction has gained a lot of support in the last years by the huge amount of data obtained by imaging studies, by experimental molecular biology and pharmacology. Development of addiction, addiction memory, craving and relapse result from neurobiological mechanisms. Only recently some researchers tried to put together the many pieces of neurobiological knowledge to obtain more integrated views.

The functional relevance of macrocircuits in the brain – e.g. projections from the prefrontal cortex to subcortical areas or projections from the midbrain to limbic structures – can be seen now in an operationally closed network that controls the behavior by the dynamic balance of mutual inhibition and activation between the brain stem, basal ganglia and cortex. The loss of behavioral control can be explained by a dysfunctional network activity between these interacting centers. In this regard, it has to be acknowledged that the most important theoretical steps were made by understanding the brain as a system of closed loops that are able to optimize themselves.

The opponent-process theory of Solomon can now be turned into a neurobiological theory as proposed by George Koob and Michel LeMoal in their concept of “allostatic” and homeostatic neuronal mechanisms. This model allows for understanding the dynamics of the development of addiction on a macro- (and micro-)level of the brain. This includes the local neuronal networks of the various nuclei in the brain (e.g. Nucleus accumbens, Amygdala). On that level, it is important to understand the interactions between the various neurochemical systems like glutamate, dopamine, serotonin and GABA converging onto these nuclei (“neurochemical mobile”). These molecular mechanisms have been analyzed in detail by the work of Eric Nestler and his group.

Finally, on the molecular level of the synapses and also with regard to intracellular signaling networks, a comprehensive understanding of the single cell as a living system is required.

The main challenge of understanding addiction from a systemŽs perspective is the structural and functional complexity of the brain. For this reason, theoretical neuropsychiatry of addiction needs the tools of systems science like systemic modeling and computer simulations.

To this end, we started a series of workshops in 2005 on “Computational Neuropsychiatry” to bring together psychiatry with computational modeling in theoretical neuroscience. These workshops are designed as informal meetings between theoreticians such as systems scientists, computational scientists and empirical researchers such as neuropsychiatrists and neurobiologists.The first workshop was attended – amongst others – by Arvid Carlsson, whose models of networks in schizophrenia were vividly discussed. The second workshop in 2006 was intended to discuss clinical and experimental data and theoretical concepts of disturbances of the working memory as they are observed in patients with schizophrenia.

In the 2007 workshop, we discussed the perspective of Molecular Systems Biology on schizophrenia, and in 2008, Systems Biology of Addiction has been on the agenda. This workshop kindly was supported by Essex GmbH, Pfizer GmbH, Sanofi-Aventis GmbH, Ruma GmbH and von Minden GmbH.

In 2009 we are going to discuss the Systems Biology of synapses in mental disorders.

These activities reflect how fruitful and interactive this research area has developed within the last years.

F. Tretter, P. J. Gebicke-Haerter, A. Heinz

Munich, Mannheim and Berlin

May 2009

Correspondence