Fabp7 maps to a quantitative trait locus for a schizophrenia endophenotype

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Prepulse inhibition (PPI) deficits are a key biological marker for schizophrenia.
• Understanding the genetic and molecular mechanisms controlling PPI is crucial for schizophrenia research.

Purpose of the Study:

• To identify quantitative trait loci (QTL) associated with PPI and related behaviors.
• To investigate the role of a candidate gene, Fabp7, in PPI and schizophrenia pathology.

Main Methods:

• Quantitative trait loci (QTL) analysis in 1,010 F2 mice from a cross of high-PPI (C57BL/6) and low-PPI (C3H/He) strains.
• Phenotypic analysis of Fabp7-deficient mice, including PPI, acoustic startle response, and neurogenesis.
• Genetic association and expression analysis of human FABP7 in schizophrenia patient brains.

Main Results:

• Six major QTL for PPI, six for acoustic startle response, and four for latency to response peak were detected, some sex-dependent.
• Fabp7 was identified as a promising candidate gene on Chromosome 10, showing links to NMDA receptors and astrocytes.
• Fabp7-deficient mice exhibited decreased PPI and shortened startle latency; disruption of Fabp7 attenuated neurogenesis.
• Human FABP7 showed altered expression and genetic association with schizophrenia, particularly in males.

Conclusions:

• Fabp7 plays a significant role in PPI and is implicated in schizophrenia pathology, potentially through NMDA receptor, neurodevelopmental, and glial pathways.
• The effects of Fabp7 on PPI and schizophrenia may be more pronounced in males.
• Fabp7 represents a novel link between neurodevelopment, glial function, and schizophrenia, with implications for fetal programming.