The gene expression profile in the hypothalami of the Wfs1 mutant mice was significantly similar to the profiles of following biological functions: psychological disorders, bipolar disorder, mood disorder.
These results suggest that the therapeutic effects of valproate in bipolar disorder may be mediated by WFS1 expression and its dissociation from GRP94.
Because WfS1, the causative gene of Wolfram disease, is located at 4p16, a linkage locus for bipolar disorder, mutations of WfS1 were suggested to be involved in the pathophysiology of bipolar disorder.
Various other protein products of genes associated with bipolar disorder either bind to or are affected by phosphatidyl-inositol phosphate products of this pathway (ADBRK2, HIP1R, KCNQ2, RGS4, WFS1), are associated with its constituent elements (BCR, DUSP6, FAT, GNAZ) or are downstream targets of this signalling cascade (DPYSL2, DRD3, GAD1, G6PD, GCH1, KCNQ2, NOS3, SLC6A3, SLC6A4, SST, TH, TIMELESS).