TITLE:
Self-Frustration of Expectations in Major Depressive Disorder: The Syncytiopathy Hypothesis of Depression Revisited
AUTHORS:
Bernhard J. Mitterauer
KEYWORDS:
Major Depression, Glial Syncytiopathy, Protracted Information Processing, Self-Frustration of Expectations, Cognitive Impairment
JOURNAL NAME:
Advances in Bioscience and Biotechnology,
Vol.14 No.12,
December
28,
2023
ABSTRACT: 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.