Author(s)

Bernhard J. Mitterauer

Volitronics Institute for Basic Research, Psychopathology and Brainphilosophy, Wals, Salzburg, Austria.

This paper is a further elaboration of my model of the pathophysiology of major depressive disorder focusing on imbalances of glial-neuronal interactions in tripartite synapses and the glial network (syncytium). Basically, it is proposed that the connexin proteins building gap junctions in the glial syncytium are underexpressed or dysfunctional in major depression, called syncytiopathy. As a compensatory effect the astrocytic receptors in tripartite synapses are overexpressed. This leads to protracted synaptic information processing because of a relative lack of neurotransmitter substances for the occupancy of astrocytic receptors. Based on a new biophysical formal description of astrocytic receptors as expectation variables it can be shown that the protracted processing of sensory information frustrate the full comprehension of the expected event, since it cannot be grasped in time. Moreover, expectation frustration may stress the glial syncytium aggravating memory impairment. This cyclic process of dysbalanced synaptic information processing is characterized as self-frustration of expectations explanatory for the main cognitive dysfunctions in major depression as slowing down processing speed, deficits in attention and working memory. The main result of the study is that patients with major depression cannot fully acknowledge the existence of an intended event.

Major Depression, Glial Syncytiopathy, Protracted Information Processing, Self-Frustration of Expectations, Cognitive Impairment

Mitterauer, B. (2023) Self-Frustration of Expectations in Major Depressive Disorder: The Syncytiopathy Hypothesis of Depression Revisited. Advances in Bioscience and Biotechnology, 14, 534-544. doi: 10.4236/abb.2023.1412037.