Editorial

Today, the scientific basis of biological psychiatry goes back to an already enormous but still constantly increasing set of neurobiological data, coming from histological, electrophysiological, pharmacological, biochemical, genetical and, of course, brain imaging studies. However, attempts to combine or integrate this vast amount of data from different fields to form a comprehensive concept about the pathophysiology of specific psychiatric disorders have not yet been too many. Thus, the scientific field of “theoretical psychiatry” is not yet really developed. For this reason it seems to be necessary and fruitful to integrate our today's know-how of theoretical neurobiology usually called “Computational Neuroscience” into the field of neuropsychiatry. Consequently, we initiated a series of workshops an “Computational Neuropsychiatry” beginning in 2005 at the mental hospital Haar (Munich/FRG). We started with the work of Arvid Carlsson about the possible rote of several specific neuronal loops for pathophysiology and therapy of schizophrenia. At this workshop we had the chance to discuss with him the theoretical concepts that he proposed already many years before. Physicists, mathematicians and computational scientists were integrated in this workshop with psychiatrists and pharmacologists, whose lectures were published in 2006 as a Supplement volume of Pharmacopsychiatry.

Because of the considerable success of this first meeting we proceeded in our attempts to integrate computational neuroscience with biological psychiatry. Our second workshop was focussing on the role of dopamine in working memory deficits in schizophrenia, presumably related to dysfunctions of prefrontal cortical networks. The presentations of this meeting, together with some additional papers related to the topic are summarized in the present supplement of Pharmacopsychiatry as Vol. 2 devoted to “Computational Neuropsychiatry”.

Increasing evidence suggests that the previously rather neglected cognitive symptoms in schizophrenia may be key features to understand the neurobiological basis of this disease. Cognitive symptoms in schizophrenia have been associated with impairment of working memory which is regulated in part by dopaminergic mechanisms in the prefrontal cortex. Quite interestingly, the most robust findings of imaging studies in schizophrenia relate to hypofunction of the dorsolateral prefrontal cortex (PFC) as shown by many fMRI studies. This observation seems to be correlated with a dysfunction of PFC dopamine regulation leading to an impairment in certain tasks of working memory performance. The central role of dopamine in working memory dysfunctions is related to a reduced D1 receptor-based signalling compared to D2 receptor activation. This causal relationship between working memory deficits and dopamine in PFC is further put forward by the differential effects of conventional and atypical antipsychotics in PFC. In agreement with the better therapeutic effects of the atypicals on cognitive symptoms, many atypicals elevate dopamine in PFC, while the conventional antipsychotics have little effects in this respect. Thus, conventional and atypical neuroleptics may additionally represent tools to further understand the role of dopamine for cognitive symptoms of schizophrenic and of the neuronal network involved. Thus, the interplay of neurobiological and neuropsychological functions related to PFC represents an interesting framework for computational neuropsychiatry. Much of the work done in this field and many future perspectives are summarized in the many excellent contributions to this supplement volume. We are very grateful to all who made this possible.

As the field is rapidly moving, our 2007 workshop on Computational Systems Biology and psychiatry was addressing the dopaminergic intracellular signalling network as an important molecular microcircuitry relevant to symptomatic and therapeutic aspects of schizophrenia. The proceeding will be published as Vol. 3 of our Pharmacopsychiatry series “Computational neuropsychiatry” in 2008. The next workshop planned for May 2008, will address neuronal networks relevant for addiction.

We gratefully acknowledge that workshop and publication have only been possible by generous educational grants by Lilly, Lundbeck, Janssen-Cilag and Bristol-Meyers Squibb.

F. Tretter, W. E. Müller

Munich and Frankfurt

November 2007

Correspondence