A psychobiological model of the etiopathology of bipolar disorder is proposed. Based on genetic-epigenetic and chronobiological factors a hyperintentional personality structure, if faced with non-feasible intentional programs in the environment, suffers from inner and outer stress. This stress situation leads to imbalances in information processing in glial-neuronal synaptic units, called tripartite synapses. In depression the overexpression of astrocytic receptors and of gap junctions in the astroglial network causes a prolonged information processing which affects the behavior generating systems in the brainstem reticular formation. Because the activation of the behavior generating systems is protracted, they are unable to select an appropriate mode of behavior (e.g. communicating, eating, working, sleeping, etc.) from sensory information in real time. Inversely, in mania astrocytic receptors and gap junctions are underexpressed causing a shortened synaptic information processing with rapid changes in behavior. Switching may represent a coping-attempt with depression by mania and vice versa. Towards a comprehensive model of the pathophysiology of bipolar disorder the role of microglia and their devastating effects on glial-neuronal interactions are outlined. Finally, the testing of the model is discussed.
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