The association of depression and anxiety with cardiac autonomic activity: The role of confounding effects of antidepressants

an article by Mandy X. Hu, Yuri Milaneschi, Femke Lamers and Brenda W. J. H. Penninx (Vrije Universiteit Amsterdam,The Netherlands), Ilja M. Nolte and Harold Snieder (University of Groningen, The Netherlands) and Conor V. Dolan and Eco J. C. de Geus (VU University, Amsterdam, The Netherlands) published in Depression and Anxiety Volume 36 Issue 12 (December 2019)

Abstract

Background
Depression and anxiety may unfavourably impact on cardiac autonomic dysregulation. However, it is unclear whether this relationship results from a causal effect or may be attributable to confounding factors. We tested the relationship between depression and anxiety with heart rate (HR) and heart rate variability (HRV) across a 9‐year follow‐up (FU) period and investigated possible confounding by antidepressant use and genetic pleiotropy.

Methods
Data (no. of observations = 6,994, 65% female) were obtained from the longitudinal Netherlands Study of Depression and Anxiety, with repeated waves of data collection of HR, HRV, depression, anxiety, and antidepressant use. Summary statistics from meta‐analyses of genome‐wide association studies were used to derive polygenic risk scores of depression, HR, and HRV.

Results
Across the 9‐year FU, generalised estimating equations analyses showed that the relationship between cardiac autonomic dysregulation and depression/anxiety rendered nonsignificant after adjusting for antidepressant use. A robust association was found between antidepressant use (especially tricyclic antidepressants, selective serotonin, and noradrenalin reuptake inhibitors) and unfavourable cardiac autonomic activity across all waves. However, no evidence was found for a genetic correlation of depression with HR and HRV, indicating that confounding by genetic pleiotropy is minimal.

Conclusions
Our results indicate that the association between depression/anxiety and cardiac autonomic dysregulation does not result from a causal pathway or genetic pleiotropy, and these traits might therefore not be inevitably linked. Previously reported associations were likely confounded by the use of certain classes of antidepressants.

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