S1P also acts as an intracellular inhibitor of histone-deacetylase (HDAC) 1 and 2.50 Higher expression of HDAC1/HDAC2 (Hdac2) was reported in patients with schizophrenia and schizophrenia model rats.51–54 Furthermore, mice overexpressing Hdac1 in the prefrontal cortex displayed working-memory impairment.53,55 Therefore, lowered S1P levels may contribute to schizophrenia pathophysiology through the upregulation of HDAC1 and HDAC2 activities. This evidence concerns the gene HDAC2 and schizophrenia.