The loss of self-boundaries: towards a neuromolecular theory of schizophrenia.
I start out with the hypothesis that the basic symptoms of schizophrenia are caused by a loss of self-boundaries. Phenomenologically, schizophrenic symptoms are based on the inability of the brain to delimit conceptual boundaries. At the cellular level in the brain, I have in previous work attributed a spatio-temporal boundary setting function to the glial cells such that glial cells determine the grouping of neurons into functional units. Mutations in genes that result in non-splicing of introns can produce aberrant versions of neurotransmitter receptors that lack protein domains encoded by entire exons and can also have protein sequence encoded by introns that have not been properly spliced out. I propose that such "chimeric" receptors are generated in glial cells and that they cannot interact properly with their cognate neurotransmitters. The glia will then lose their inhibitory function with respect to the information processing within neuronal networks. The loss of glial boundary-setting may result in a 'borderless' generalization of information processing such that the structuring of the brain in functional domains is almost completely lost. This loss of glial boundary setting could be an explanation of the loss of self-boundaries in schizophrenia.
Mitterauer
B J
BJ
Institute of Forensic Neuropsychiatry and Gotthard Günther Archives, University of Salzburg, Ignaz-Harrer-Strasse 79, A-5020 Salzburg, Austria. bernhard.mitterauer@sbg.ac.at
D017398:Alternative Splicing; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000473:pathology; D006801:Humans; D007438:Introns; D008954:Models, Biological; D009154:Mutation; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000378:metabolism*; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology*