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

Mandy X. Hu, Yuri Milaneschi, Femke Lamers, Ilja M. Nolte, Harold Snieder, Conor V. Dolan, Brenda W.J.H. Penninx, Eco J.C. de Geus

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Depression and anxiety may unfavorably 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, generalized 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 unfavorable 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.

Original languageEnglish
Pages (from-to)1163-1172
Number of pages10
JournalDepression and Anxiety
Volume36
Issue number12
Early online date1 Jan 2019
DOIs
Publication statusPublished - 1 Dec 2019

Cite this

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title = "The association of depression and anxiety with cardiac autonomic activity: The role of confounding effects of antidepressants",
abstract = "Background: Depression and anxiety may unfavorably 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, generalized 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 unfavorable 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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author = "Hu, {Mandy X.} and Yuri Milaneschi and Femke Lamers and Nolte, {Ilja M.} and Harold Snieder and Dolan, {Conor V.} and Penninx, {Brenda W.J.H.} and {de Geus}, {Eco J.C.}",
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The association of depression and anxiety with cardiac autonomic activity : The role of confounding effects of antidepressants. / Hu, Mandy X.; Milaneschi, Yuri; Lamers, Femke; Nolte, Ilja M.; Snieder, Harold; Dolan, Conor V.; Penninx, Brenda W.J.H.; de Geus, Eco J.C.

In: Depression and Anxiety, Vol. 36, No. 12, 01.12.2019, p. 1163-1172.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - The association of depression and anxiety with cardiac autonomic activity

T2 - The role of confounding effects of antidepressants

AU - Hu, Mandy X.

AU - Milaneschi, Yuri

AU - Lamers, Femke

AU - Nolte, Ilja M.

AU - Snieder, Harold

AU - Dolan, Conor V.

AU - Penninx, Brenda W.J.H.

AU - de Geus, Eco J.C.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Background: Depression and anxiety may unfavorably 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, generalized 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 unfavorable 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.

AB - Background: Depression and anxiety may unfavorably 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, generalized 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 unfavorable 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.

KW - antidepressants

KW - anxiety/anxiety disorders

KW - depression

KW - electrophysiology

KW - gene-environment

KW - genetics

KW - stress

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U2 - 10.1002/da.22966

DO - 10.1002/da.22966

M3 - Article

VL - 36

SP - 1163

EP - 1172

JO - Depression and Anxiety

JF - Depression and Anxiety

SN - 1091-4269

IS - 12

ER -