The glial growth factors deficiency and synaptic destabilization hypothesis of schizophrenia. The hypothesis is depicted in form of the multifactorial-threshold model for schizophrenia developed by Gottesman and Shields  and postulates that several genes (e.g., NRG1, TNF, GAS6, INF1 etc.) and environmental factors influence the positive feedback loop between the presynaptic neuron and its target cells. The hypothesis assumes that the baseline strength of synaptic connections is normally distributed in the general population, such that those whose synaptic strength falls below a certain threshold develop synaptic destabilization and schizophrenic symptoms. The strength of the growth signaling correlates with the efficacy and stability of the synaptic connection. Environmental and genetic factors increase or decrease growth signaling and in consequence synaptic strength. Viruses may cause synaptic destabilization by triggering the release of neurotoxic cytokines from glial cells or by decreasing the synthesis of GGFs via a reduction of the protein-synthesis rate in viral infected glial cells.
Moises et al. BMC Psychiatry 2002 2:8 doi:10.1186/1471-244X-2-8