A pathophysiological model of the loss of reality comprehension in schizophrenia is proposed. Based on a formalism it is hypothesized that astroglial domains exert an information-categorizing function which becomes progressively lost in the schizophrenic process, caused by functional and structural disintegration of astroglial domains. Unconstrained synaptic neurotransmission functionally disintegrates the astroglial domains. Microdomains located between perisynaptic astroglial processes and the synaptic membrane are interpreted as elementary functional units categorizing synaptic information processing. Unconstrained diffusion of neurotransmitters into the extrasynaptic space leads to the dysfunction of microdomain formation. In parallel, atrophic processes of astroglia progressively break up the connectivity between synaptic and extrasynaptic compartments disrupting astroglial domains. Basically, the organization of astroglia into definite functional and structural units (modules) of astroglial-synaptic information processing may enable the brain to comprehend ontological realms such as subjects and objects in the environment and their distinct qualities. This fundamental capability of cognition is lost in schizophrenia. It is suggested that this ontological confusion of astroglial domain boundaries progressively disorganizes reality comprehension and may represent the basic pathology in schizophrenia underlying the main symptoms of the disorder. Finally, the testing of the model is shortly discussed.
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