Understanding the mechanisms of sudden cardiac death in bipolar disorder: Functional asymmetry in brain-heart interactions as a potential culprit

Kate Levenberg, Hugo D. Critchley, Richard D. Lane

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The risk of sudden cardiac death is remarkably high in patients with bipolar disorder. The risk is especially elevated, 32 times greater than in the general population, in patients younger than 30 years old. Early atherosclerosis and general lifestyle risk factors might play a role but are insufficient to account for this greatly inflated risk of sudden cardiac death. A recent mechanistic model of the pathophysiology of bipolar disorder highlights dysfunctional changes in functional hemispheric lateralization that are proposed to arise as a consequence of aberrant midbrain signaling at the level of the paraventricular nucleus of the hypothalamus. The paraventricular nucleus is also a key region involved in regulating bodily physiology, including the balanced autonomic control of cardiac function. Further, the sympathetic innervation of the heart is configured anatomically such that exaggerated imbalanced right-left stimulation of the heart can predispose to fatal arrhythmia. Correspondingly, lateralization of cortical activity related to emotional arousal and acute stress, if not otherwise corrected, may drive asymmetric sympathetic effects on the heart. In cardiac patients, asymmetric midbrain lateralization is associated with increased proarrhythmic changes during mental and physical stress challenges, predisposing vulnerable patients to lethal arrhythmias. Here, we propose that similar mechanisms involving lateralized brain–heart interactions account for the increased risk of sudden cardiac death in patients with bipolar disorder. We explore the evidence for, and implications of, this model.

Original languageEnglish (US)
Article number110986
JournalMedical Hypotheses
Volume170
DOIs
StatePublished - Jan 2023

Keywords

  • Asymmetry
  • Bipolar Disorder
  • Manic-Depressive Disorder
  • Mortality
  • Paraventricular Nucleus
  • Sudden Cardiac Death

ASJC Scopus subject areas

  • General Medicine

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