Editorial

Over the last decades, biological psychiatry has provided tremendous insight into brain mechanisms underlying psychiatric diseases. Imaging studies, partially also including psychopharmacological and functional intervention techniques, strongly suggest that only distinct structures of the brain are specifically disturbed in the individual diseases. For schizophrenia, the hypothesis of a hyperactivity of the striatal dopaminergic transmission was extremely fruitful. Experimental and clinical evidence related to amphetamine-induced behavioral changes in animals and psychotic states in man and the antipsychotic effects of D2 receptor blocking agents are all together giving strong evidence supporting the hypothesis of hyperactivity of the subcortical dopaminergic system. Moreover, the cortical dopaminergic transmission seems to be rather hypoactive, strongly supporting the concept of regional specific changes of brain function in psychiatric disorders. To explain hyperactivity in one region and hypoactivity in another one, regional changes of the complex mechanisms of dopaminergic neurotransmission need to be considered. Several subtypes of dopamine receptors, their topographical distribution in the brain, the difference of presynaptic and postsynaptic D2 receptors, of intra- and extrasynaptic D2 receptors, the role of dendritic or somatic receptor locations, phasic and tonic discharge patterns of different dopamine neurons all are finally leading to a regional different pattern of dopaminergic activity. To identify the specific role of these regional changes for the complex symptoms of schizophrenia represents the major challenge of to day's and future research is this disorder.

Additionally, drug-induced psychoses by LSD, mescaline or other 5-HT-agonists as well as the introduction of atypical antipsychotics as potent 5-HT-antagonists suggest hyperactivity of serotoninergic neurotransmission as a relevant factor for at least some symptoms of schizophrenia. Furthermore, experimental and clinical evidence established that hypoactivity of glutamatergic transmission is involved in psychotic states. Finally, there is growing evidence that deficiency of GABAergic transmission might also be involved in schizophrenia. For each of these transmission systems a very complex picture is emerging from a molecular biological data set. Therefore, we are facing the task to build together the individual data into a coherent complex model of the molecular mechanisms being involved in schizophrenia.

For this reason it seems to be a fruitful aim to integrate ”systems science” or ”computational science” into the efforts to build theoretical models in biological psychiatry. Systems science, originated as general systems theory by the biologist Ludwig von Bertalanffy is a field that has developed since the 60ies and 70ies of the 20^th century partially related to ”cybernetics” of Norbert Wiener and William Ross Ashby. The aim of those fields is to understand information processing in living systems and machines. Some authors still prefer the term cybernetics some others refer to ”informatics”, others talk about ”computational sciences” or ”computational neuroscience”, lately the term ”systems biology” was created. Much is written about differences, similarities and communities of these areas which we do not consider here in detail. As the brain is a structure with innumerable connected feedback loops we think that the approach of systems science might be appropriate. The basis of this approach is mathematics. Although in neurobiology research several applications of mathematical theories were made already in the 60ies and 70ies, applications in psychiatry are not frequent. Mainly the concept of artificial neural networks was used to simulate some cognitive disorders and symptoms of schizophrenia.

Up to now, there is still not much exchange between biological psychiatry and systems science (or computational science). In order to signify the importance of systemic thinking in neurobiology we use the term ”Systems Science” not saying that there is a crucial difference to the presently more often used term ”computational neuroscience”.

For this reason, in October 2005 on occasion of the 100^th anniversary of the State Mental Health Hospital Haar (Munich) we organized a workshop entitled, ”Systems Theory and Neurobiology of Schizophrenia”, where neurobiological models constructed by Arvid Carlsson and related models were presented and discussed by several psychiatrists and systems scientists[1]. It is our hope that this effort will bridge the gap between biological psychiatry and systems science. We are happy to present contributions and discussions related to the workshop in the present special issue.

We hope that not only the usefulness but also the necessity of integration of theoretical sciences into biological psychiatry and pharmacopsychiatry will become evident. We are confident that there will be more joint ventures of that type in near future.

December 2005

Felix Tretter (Haar/Munich, Germany)

Walter E. Müller (Frankfurt, Germany)

Arvid Carlsson (Göteborg, Sweden)

1 Acknowledgements
This project was supported by an educational grant from Bristol Myers Squibb GmbH & Co KG aA Germany and Otsuka Pharmaceuticals