Bipolar Patient–Specific In Vitro Diagnostic Test Reveals Underlying Cardiac Arrhythmia Phenotype Caused by Calcium Channel Genetic Risk Factor

• DOI: 10.1016/j.bpsgos.2024.100296
• Publication Date: 2024-02-20T21:08:04Z
• Authors: Rachel Dow; Cindy DeLong; Guihua Jiang; Durga Attili; Jeffery Creech; Rachel Kraan; Katherine Campbell; Prakaimuk Saraithong; Sue O’Shea; Andre Monteiro da...; Melvin G. McInnis; Todd J. Herron
• Keywords: Psychiatry; Induced pluripotent stem cells; 0303 health sciences; 03 medical and health sciences; Bipolar genetic risk factor; Cardiac electrophysiology; RC435-571; Techniques and Methods; Personalized medicine, Cardiac Regeneration

A common genetic risk factor for bipolar disorder is the CACNA1C gene, a gene also critical cardiac rhythm. The impact of mutations on patient rhythm unknown. Here we report electrophysiological implications associated in using induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs). Results indicate related mutation causes electrical impulse conduction slowing mediated by impaired intercellular coupling via connexin43 gap junctions. In vitro therapy to restore expression increased velocity and protected against thioridazine QT-prolongation. Patients positive factors may have elevated proarrhythmic adverse events psychiatric medications that slow or prolong QT interval. This diagnostic tool enables specific testing determine patients' sensitivity off target effects medications.