Abstract
A psychobiological model of the etiopathology of major depression is proposed. It is hypothesized that 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 an excess of astrocytic receptors in glial-neuronal synaptic units, called tripartite synapses, and an overexpression of gap junctions in astroglial networks. The imbalance of synaptic information processing caused by the excess of astrocytic receptors leads to a protracted information processing which affects the behavior generating systems in the reticular formation in the brainstem. Since the activation of these systems is delayed, they cannot decide in real time which mode of behavior (e.g. eating, working, communicating, etc.) is appropriate to a specific sensory information from the environment. The modes of behavior comprise all psychobiological action patterns occurring in circadian time periods. A delay of synaptic activation of the systems in the brainstem reticular formation may lead to a displacement of the modes of behavior in the sense of a persistence of some modes (“must do”) and the inability to produce others (”cannot do”). Such a severe behavioral disorder also affects the self-understanding of the patient resulting in a depressive mood. The mechanism of the displacement of the modes of behavior is shown in a computer simulation. Preliminary clinical data may support the model proposed and is briefly discussed.
Highlights
The imbalance of synaptic information processing caused by the excess of astrocytic receptors leads to a protracted information processing which affects the behavior generating systems in the reticular formation in the brainstem
I hypothesize that receptors on the astrocytic membrane and gap junctions in the astroglial network are overexpressed so that the neurotransmitter substances cannot occupy the excess of astrocytic receptors in real time causing a protracted synaptic information processing (Hasler, 2010)
The main result is the following: considering that phosphorylation is a prerequisite for acute function of connexins (Solan & Lampe, 2009), the therapeutic effects of antidepressant drugs might implicate the functional inactivation of connexin 43. This finding may support my model of the pathophysiology of major depression, since it allows the interpretation that overexpressed connexins become reduced by antidepressant drugs balancing synaptic transmission
Summary
Clinical relevant neurobiological hypotheses of major depressive disorder comprise genetics, stress, chronobiology, neurochemistry (neurotransmitters, receptors etc.), and immunoendocrinology. Based on a genetic inclination to depression, stress may cause imbalances of information processing in tripartite synapses. I hypothesize that receptors on the astrocytic membrane and gap junctions in the astroglial network are overexpressed so that the neurotransmitter substances cannot occupy the excess of astrocytic receptors in real time causing a protracted synaptic information processing (Hasler, 2010). Generated in the brainstem reticular formation, is displaced caused by protracted synaptic activation (Verkhratsky et al, 2014). Dependent on the time period of protracted synaptic information processing, some modes of behavior are not activated and others persist (Mitterauer, 2009). The essential biological picture focuses on protracted information processing in tripartite synapses caused by an excess of astrocytic receptors. After the discussion of testing, the hypothetical model preliminary clinical data are reported and briefly discussed
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
