Our preliminary efforts yielded consistent results highlighting the potential role of mitochondrial health as biological predictors of lithium response in bipolar affective disorder (BPAD). Data from patient derived lymphoblastoid cell lines (LCL) indicated higher mitochondrial potential in cells from lithium non-responder than in responders. The abnormality was reversed with in-vitro Lithium, only in lithium responders. Next generation sequencing from individuals quantified for Lithium treatment response has thrown up novel variants related to mitochondrial function, and cell migration. Human induced pluripotent stem cells (HiPSC) have been generated from the above LCLs from 8 patients with BPAD (4 lithium responders and 4 lithium non-responders) HiPSCs have also been generated from familial unaffected control and healthy population controls. Lithium was found to reduce mitochondrial potential in control HiPSC derived neural stem cells in a preliminary experiment.
Collectively the current proposal aims to understand the biological hallmarks of lithium response and cellular pathogenesis of BPAD through a collaborative research effort between clinicians and basic scientists using iPS derived neural stem cells and neurons. Our primary research focus will be on two areas of BPAD biology:
1. Role of mitochondrial signaling in dictating lithium response in BPAD patients.
2. Role of Inter-genomic cross talks between mitochondria and nuclear genes in BPAD pathogenesis.