Editorial

Synapses are essential functional units of neurons in complex neuronal networks. Disturbances of their functions can have profound consequences and lead to psychiatric disorders. For instance, in schizophrenia and addiction the influence of dopamine synapses is being discussed, whereas norepinephrine and serotonin synapses appear to be major players in depression. Various treatments of these diseases try to influence synaptic transmission by molecular switches such as receptor blockades, reuptake blockers or by inhibiting enzymatic degradation of transmitters, etc. This means that not only synaptic molecular mechanisms, but also electrophysiological properties can be modulated. Often, significant treatment takes as long as 10 days to show any effect. Although important progress has been made in the treatment of mental disorders, psychopharmacological treatment is not entirely satisfying, especially regarding its side effects. It follows, that we do not sufficiently understand the dynamics of pathology and the reorganization of synapses. For this reason, the dynamics of various components of synaptic transmission should be studied further: e. g. the kinetics of control of synthesis, storage, release, reuptake, degradation, receptor occupation, up-, and down-regulatory events.

First models representing these mechanisms are presented in the accordant scientific literature: Modelling the synthesis of dopamine, modelling the transmission from electrical signalling to intrasynaptic transmitter concentration and to postsynaptic electrical singalling.

It seems useful to compare these models regarding their concepts of the neuropathology of mental disorders and their effects in terms of psychopharmaceuticals.

This approach is fundamental to the molecular biological research, integrating more and more the perspective of systems biology. Systems biology aims to reconstruct the cell on the basis of molecular biological data. This “bottom-up” reconstruction is based on quantitative kinetic data that are integrated in mathematical models transformed into computerized models. By creating these models “in-silico”, computational experiments can be performed that help to understand processes in complex networks of chemical pathways.

In 2005, we started a series of workshops on “Computational Neuropsychiatry”, with the aim to combine the views of clinical psychiatry with experimental neurobiology and computational sciences. We began with a workshop led by Arvid Carlsson and discussed his models of networks in schizophrenia. In 2006, we organized a second workshop in order to discuss clinical and experimental data and theoretical concepts of disturbances of working memory, the way it is observed in patients with schizophrenia. A year later, we discussed the perspective of molecular systems biology on schizophrenia. In 2008, we applied these experiences to addiction diseases.

There we report on our discussion of the systems biology of the synapse that was organized in 2009.

That workshop kindly was supported by Essex, Bristol-Myers Squibb, BioSim, EU-Network of Excellence and Helmholtz Zentrum.

It is our aim to initiate and increase cooperation between researchers in this field and to pursue questions like, whether or not theoretical neuropsychiatry can gain from using the tools of systemic modeling and computer simulations.

F. Tretter, D. Rujescu, O. Pogarell, E. Mendoza

Haar/Munich and Munich

May 2010

Correspondence