The R771H variant in the mineralocorticoid receptor may increase risk of psychiatric and medical disorders: An exploratory case series

Research has found that the genetic risk of developing psychiatric disorders is both polygenic and pleiotropic indicating that multiple different genetic variants may increase the risk of multiple disorders.Therefore, an urgent need exists to identify specific genetic variants that increase risk of psychiatric disorders to inform the development of targeted treatments for negative affective states including depression and anxiety.Here we report a case series of three patients with an arginine to histidine substitution at position 771 of the mineralocorticoid receptor (encoded by the NR3C2 gene).These patients exhibit a pattern of eating disorders, treatment resistant depression, anxiety, and insomnia, which is consistent with previous finds in genomewide association studies.Off-label use of the mineralocorticoid antagonist spironolactone was well tolerated and reported to be beneficial for mood symptoms in two of the three cases.Identification of the MR R771H variant may define a group of patients with treatment-resistant mood disorders that could benefit from an alternative treatment approach.