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- Title
The glial growth factors deficiency and synaptic destabilization hypothesis of schizophrenia.
- Authors
Moises, Hans W.; Zoega, Tomas; Gottesman, Irving I.
- Abstract
Background: A systems approach to understanding the etiology of schizophrenia requires a theory which is able to integrate genetic as well as neurodevelopmental factors. Presentation of the hypothesis: Based on a co-localization of loci approach and a large amount of circumstantial evidence, we here propose that a functional deficiency of glial growth factors and of growth factors produced by glial cells are among the distal causes in the genotype-to-phenotype chain leading to the development of schizophrenia. These factors include neuregulin, insulin-like growth factor I, insulin, epidermal growth factor, neurotrophic growth factors, erbB receptors, phosphatidylinositol-3 kinase, growth arrest specific genes, neuritin, tumor necrosis factor alpha, glutamate, NMDA and cholinergic receptors. A genetically and epigenetically determined low baseline of glial growth factor signaling and synaptic strength is expected to increase the vulnerability for additional reductions (e.g., by viruses such as HHV-6 and JC virus infecting glial cells). This should lead to a weakening of the positive feedback loop between the presynaptic neuron and its targets, and below a certain threshold to synaptic destabilization and schizophrenia. Testing the hypothesis: Supported by informed conjectures and empirical facts, the hypothesis makes an attractive case for a large number of further investigations. Implications of the hypothesis: The hypothesis suggests glial cells as the locus of the genesenvironment interactions in schizophrenia, with glial asthenia as an important factor for the genetic liability to the disorder, and an increase of prolactin and/or insulin as possible working mechanisms of traditional and atypical neuroleptic treatments.
- Subjects
NEUROGLIA; GROWTH factors; GENETICS of schizophrenia; INSULIN; CELL receptors; TUMOR necrosis factors; GLUTAMIC acid
- Publication
BMC Psychiatry, 2002, Vol 2, p8
- ISSN
1471-244X
- Publication type
Article
- DOI
10.1186/1471-244X-2-8