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

Abstract

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.

Keywords:

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

Authorship

Dr. Halaris designed the study, wrote the protocol, and oversaw the preparation of the manuscript. Brandon Hage actively participated in data collection, data analyses, literature search and preparation of all drafts of the manuscript. Briana Britton contributed to data management and data analyses. Dr. Daniels participated in the clinical portions of the study and data collection. Dr. Heilman performed data analyses. Dr. Porges oversaw data analyses contributed to manuscript preparation, and acted as a consultant to the co-investigators.

Acknowledgements

The authors gratefully acknowledge the support of the Stanley Medical Research Institute that awarded a grant to Dr. A. Halaris for his studies in bipolar disorder.

Statement of interest

None to declare.