Neurodevelopmental hypothesis of schizophrenia and involvement of essential fatty acid

Deficits in prepulse inhibition (PPI) are a biological marker for schizophrenia. To unravel the mechanisms that control PPI, we performed quantitative trait loci (QTL) analysis, on 1010 F2 mice derived by crossing C57BL/6 (B6) animals that show high PPI with C3H/He (C3) animals that show low PPI. We detected 6 major loci for PPI. A promising candidate on the chromosome 10-QTL was Fabp7 (fatty acid binding protein 7, brain), a gene with functional links to the NMDA receptor and expression in neural stem/progenitor cells in developmental stage. Fabp7-deficient mice indeed showed decreased PPI. A quantitative complementation test supported Fabp7 as a potential PPI-QTL gene. Disruption of Fabp7 attenuated neurogenesis in vivo. Human Fabp7 showed genetic association with schizophrenia. FABP7 is known to have high affinity for polyunsaturated fatty acids, in particular docosahexaenoic acid. These results suggest that FABP7 plays a novel and crucial role, linking the NMDA, neurodevelopmental and nutritional issues of schizophrenia pathology.