Fibroblast growth factors in schizophrenia

Abstract

A large association study by O'Donovan et al recently suggested that genetic variation in fibroblast growth factor receptor (FGFR) 2 increases the risk for developing schizophrenia. Fibroblast growth factors (FGFs) are part of the family of glial growth factors; they control the growth and patterning of specific brain structures and regulate the maintenance and repair of neuronal tissues. In addition, a direct interaction was recently found between FGFRs and adenosine A(2A) receptors, leading to corticostriatal plasticity and antagonizing the signaling pathway of dopamine D(2) receptors. These findings make FGFs plausible candidate genes for schizophrenia. Here, we review the role of FGFs in schizophrenia and combine evidence from studies on variations in FGF genes, RNA expression, protein levels, and FGF administration, as well as the effects of medication and environmental risk factors for schizophrenia. These data suggest that changes in the FGF system contribute to schizophrenia and possibly to a wider range of psychiatric disorders. The role of FGFs in schizophrenia and related disorders needs to be studied in more detail.

Fig. 1.

The Structure of FGF Ligands. All FGFs consist of 2 highly conserved core domains, separated by a central spacer region of variable length; the C- and N- terminal regions also differ in length.

Fig. 2.

Fibroblast Growth Factor (FGF) Receptor Complex and Its Schematic Signaling Pathway. After ligand binding, a complex of 2 FGF molecules, bound to a receptor and linked by heparan sulphate proteoglycan, is formed. This can activate the Stat 1 or the ERK1/2 pathway.