Decreased spine density in hippocampal pyramidal neurons was also observed in Bace1-/- mice via NRG1/ErbB4 signal pathway regulation (Savonenko et al., 2008), suggesting that disturbed NRG1/ErbB4 signaling pathways in the Bace1-/- mouse model may contribute to the pathophysiology of schizophrenia. This evidence concerns the gene ERBB4 and schizophrenia.