Deficient LEF1 expression is associated with lithium resistance and hyperexcitability in neurons derived from bipolar disorder patients

Santos R, Linker SB, Stern S, Mendes APD, Shokhirev MN, Erikson G, Randolph-Moore L, Racha V, Kim Y, Kelsoe JR, Bang AG, Alda M, Marchetto MC, Gage FH.

Molecular Psychiatry, 2021


The first-line long-term treatment for bipolar disorder (BD) is lithium.   iPSC-neuron modeling of BD from lithium responsive and non-responsive individuals showed neuron hyperexcitability being reversed in lithium responsive neurons.  In this study, the authors found that the activity of the Wnt/β-catenin signaling pathway in non-responsive neurons was severely affected.  Results showed that valproic acid reduced the excitability of non-responsive neurons and was connected to changes in the Wnt/β-catenin signaling pathway.