Systems Biology of Oscillatory Processes in Sleep and Mental Disorders

From a biological point of view, mental disorders can be characterized as disturbances of complex oscillatory processes manifesting themselves on different organizational levels of the brain. One clinical example is the cyclic nature of bipolar disorders, sometimes with ultrarapid fluctuations. Regarding neurophysiology and brain electric activity, another example are certain EEG patterns indicating different modes of synchronization of neural activity. In this respect, reduced gamma activity has been found in prefrontal areas in schizophrenia. Since sleep disorders appear to be inherent in virtually all mental disorders, they are of particular interest and in the focus of studies of oscillatory processes. Onset, depth, duration, frequency, and duration of different sleep phases etc. are significantly altered in depression, bipolar disorder, schizophrenia, dementia, delirium tremens, and a wide spectrum of other disorders. Cortisol profiles and other biological parameters contribute to irregular temporal patterns in case of mental illnesses. Several replicated findings indicate that circadian and infradian rhythms of neurotransmitters as well as the endocrine system play a crucial role in this respect. A dynamic imbalance between norepinephrinergic, cholinergic and serotonergic transmission perturbs neuronal signaling, but it is unclear which of the components predominates. Reduced reactivity of feedback loops, slow on- or offset of activity of different neurotransmitter components are candidate to evoke dysfunctions in more global, higher circuits and connections, which may cause the complex symptomatology of depressive and manic states.

These findings are in line with the concept that the brain is a complex multi-level system of electrochemical oscillators from genes to global brain circuits. Very little is known about the functional consequences of the lowest level of individual genetic variation, in particular rare variants and loss-of-function de novo mutations. In order to increase our knowledge on the details of these multilevel interactions, mathematical models need to be developed for the interpretation of complex data, and computer-based simulations to invent strategies for clinical applications. In this volume of Pharmacopsychiatry, the convergence of experimental data, clinical findings and computational models will be presented. A special concern is devoted to methodological problems that are related to the complexity of biological data sets and the need to be both a “reductionist and a systems biologist too” (Bechtel).

This special volume of Pharmacopsychiatry represents the essence of a workshop on Systems Biology of Biorhythms in Sleep, Affective Disorders and Schizophrenia that was the eighth in a series of workshops on “Computational Neuropsychiatry”. These workshops aim to integrate the views of clinical psychiatry into experimental neurobiology and computational sciences.

Since these interdisciplinary initiatives are highly innovative, institutional sponsorship was hard to obtain. For this reason, we are very grateful for financial support by AGNP, Helmholtz Zentrum Munich, Bristol-Myers Squibb, AstraZeneca, Lundbeck, and Servier.

Felix Tretter, Oliver Pogarell, Dan Rujescu, Eva Meisenzahl, Hans Werner Mewes