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Carmilla M. M. Licht, MSc; Eco J. C. de Geus, PhD; Frans G. Zitman, MD, PhD; Witte J. G. Hoogendijk, MD, PhD; Richard van Dyck, MD, PhD; Brenda W. J. H. Penninx, PhD

Arch Gen Psychiatry. 2008;65(12):1358-1367.

Context  It has been hypothesized that depression is associated with lower heart rate variability and decreased cardiac vagal control. This may play an important role in the risk of cardiovascular disease among depressed individuals.

Objective  To determine whether heart rate variability was lower in depressed individuals than in healthy controls in a large adult sample.

Design  Cross-sectional analyses from a large depression cohort study.

Setting  The Netherlands Study of Depression and Anxiety.

Participants  Two thousand three hundred seventy-three individuals (mean age, 41.8 years; 66.8% female) who participated in the Netherlands Study of Depression and Anxiety. Included were 524 controls, 774 individuals with a diagnosis of major depressive disorder (MDD) earlier in life (remitted MDD), and 1075 individuals with current MDD based on the Composite International Diagnostic Interview. This sample was sufficiently powered to examine the confounding effects of lifestyle, comorbid anxiety, and antidepressants.

Main Outcome Measures  The standard deviation of normal-to-normal beats (SDNN) and cardiac vagal control, as indexed by respiratory sinus arrhythmia (RSA), were measured during 1 hours of ambulatory recording of electrocardiograms and thorax impedance. Multivariate analyses were conducted to compare SDNN and RSA across depression groups after adjustment for demographics, health, lifestyle, comorbid anxiety, and psychoactive medication.

Results  Individuals with remitted and current MDD had a lower mean SDNN and RSA compared with controls (SDNN, 3.1-5.7 milliseconds shorter, P  .02; RSA, 5.1-7.1 milliseconds shorter, P < .001; effect size, 0.125-0.269). Comorbid anxiety and lifestyle did not reduce these associations. However, accounting for psychoactive medication removed the association with SDNN and strongly attenuated the association with RSA. Depressed individuals who were using selective serotonin reuptake inhibitors, tricyclic antidepressants, or other antidepressants had significantly shorter SDNNs and RSAs (effect size, 0.207-0.862) compared with controls and depressed individuals not taking medication.

Conclusions  This study shows that depression is associated with significantly lowered heart rate variability. However, this association appears to be mainly driven by the effect of antidepressants.

Author Affiliations: Department of Psychiatry, Institute for Research in Extramural Medicine, VU University Medical Center, Amsterdam, the Netherlands (Ms Licht and Drs Hoogendijk, van Dyck, and Penninx); Department of Biological Psychology (Dr de Geus), and Center for Neurogenomics and Cognitive Research (Drs de Geus and Hoogendijk), Vrije Universiteit, Amsterdam; Department of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands (Drs Zitman and Penninx); and Department of Psychiatry, University Medical Center Groningen, Groningen, the Netherlands (Dr Penninx).

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