Low cardiac vagal tone index by heart rate variability differentiates bipolar from major depression

Brandon Hage, Briana Britton, David Daniels, Keri Heilman, Stephen W. Porges, Angelos Halaris

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Objectives: Major depressive disorder (MDD) and depression in bipolar disorder (BD) are often difficult to distinguish from each other. Autonomic nervous system (ANS) dysregulation is associated with various depressive symptoms and inflammatory response disinhibition. The beat-to-beat pattern of heart rate (heart rate variability, HRV) offers a non-invasive portal to ANS function and provides a reliable index of resting cardiac vagal tone. We quantified HRV and measured inflammatory biomarkers in MDD and BD patients in an effort to derive potential diagnostic criteria for MDD and BD. Methods: Sixty-four MDD and 37 BD patients were enrolled. HRV was assessed and blood was drawn at baseline after antidepressant washout and prior to study initiation. HRV was quantified and corrected for artefacts. Results: MDD subjects had significantly higher baseline respiratory sinus arrhythmia (P = 0.05) and LF-HRV (P < 0.01) in comparison to BD subjects. Compared to MDD subjects, BD subjects had significantly higher baseline levels of IL-10 (P < 0.01) and MCP-1 (P < 0.01). In the MDD group only, baseline LF-HRV was significantly positively correlated to baseline levels of IL-10 (r = 0.47, P < 0.01). Conclusions: Reduced vagal tone and higher levels of inflammatory biomarkers may distinguish BD from MDD and reveal an underlying pathophysiology of depression involving ANS dysfunction and chronic immune system dysregulation.

Original languageEnglish
Pages (from-to)359-367
Number of pages9
JournalWorld Journal of Biological Psychiatry
Issue number5
StatePublished - May 28 2019


  • biochemical markers
  • Bipolar affective disorder
  • heart rate variability
  • major depressive disorder
  • respiratory sinus arrhythmia


Dive into the research topics of 'Low cardiac vagal tone index by heart rate variability differentiates bipolar from major depression'. Together they form a unique fingerprint.

Cite this