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BMC Psychiatry. 2002 Jul 3;2:8.

The glial growth factors deficiency and synaptic destabilization hypothesis of schizophrenia.

Author information

1
Molecular Genetics Laboratory, Department of Psychiatry, Kiel University Hospital, Niemannsweg 147, 24105 Kiel, Germany. moises@psychiatry.uni-kiel.de

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 genes-environment 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.

PMID:
12095426
PMCID:
PMC117774
[Indexed for MEDLINE]
Free PMC Article
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