Onset of bipolar disorder by COVID-19: The roles of endogenous ouabain and the Na,K-ATPase

Abstract

Bipolar Disorder (BD) is a psychiatric disorder marked by mood swings between manic and depressive episodes. The reduction in the Na,K-ATPase (NKA) enzyme activity and the inability of individuals with BD to produce endogenous ouabain (EO) at sufficient levels to stimulate this enzyme during stressful events are factors proposed for BD etiology. According to these hypotheses, reduction in NKA activity would result in altered neuronal resting potential, leading to BD symptoms. Recently, damage to the adrenals (EO synthesis site) in coronavirus disease (COVID-19) patients has been reported, however studies pointing to the pathophysiological mechanisms shared by these two diseases are scarce. Through a literature review, this study aims to correlate COVID-19 and BD, focusing on the role of NKA and EO to identify possible mechanisms for the worsening of BD due to COVID-19. The search in the PubMed database for the descriptors (“bipolar disorder” AND “Na,K-ATPase”), (“bipolar disorder” AND “endogenous ouabain”), (“covid-19” AND “bipolar disorder”) and (“covid-19” AND “adrenal gland”) resulted in 390 articles. The studies identified the adrenals as a vulnerable organ to SARS-CoV-2 infection. Cases of adrenal damage in patients with COVID-19 showing lower levels of adrenal hormones were reported. Cases of COVID-19 patients with symptoms of mania were reported worldwide. Given these results, we propose that adrenal cortical cell damage could lead to EO deficiency following neuronal NKA activity impairment, with small reductions in activity leading to mania and greater reductions leading to depression.