Abstract

Major depressive disorder is basically a disorder of the integration of distinct time periods generated in tripartite synapses and the astroglial networks. If the sequence of time periods is dysregulated, the patient does not only suffer from emotional impairment but also from cognitive deficits dependent on the brain region affected. Since the synaptic interactions operate on feedforward and feedback mechanisms, I speak of synaptic locations of self-observation in real time periods, information processing time periods and information integration time periods. If connexins in the astroglial network are overexpressed, the number of astrocytic receptors in tripartite synapses is also overexpressed. In the case of underexpression of connexins the expression of astrocytic receptors is decreased. In both states glial-neuronal interactions are dysregulated, incapable of processing and integrating environmental information in real time. The hippocampus and the prefrontal cortex represent preferred brain regions of emotion generation and cognitive operations. In the hippocampal astroglial network both gap junctions and astrocytic receptors may be overexpressed and, as a consequence, transmitter substances cannot exert their balancing effects. Such a pathophysiological state operates hyperintentionally, since intentional programs generated in the astroglial network are not feasible in real time. Synaptic information processing is protracted and self-observation cannot take place in real time. Inversely, in the prefrontal cortex gap junctions and astrocytic receptors are underexpressed causing shortened synaptic information processing and synaptic information flooding that cannot be completely integrated in intentional programming of the astroglial network. This causes retardation of thought processes. Emotional and cognitive impairment is experienced as depressed mood. Effects of antidepressant drugs on balancing glial-neuronal interactions may be basically caused by the expression of astroglial connexin proteins representing a promising target of treatment.

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