December 1, 2008Open Access
Association Between Major Depressive Disorder and Heart Rate Variability in the Netherlands Study of Depression and Anxiety (NESDA)
Key Result
Major depressive disorder was associated with lower heart rate variability (SDNN 3.1-5.7 ms shorter, P<=0.02; RSA 5.1-7.1 ms shorter, P<0.001), an effect mainly driven by antidepressant use.
Study Design
Type
Cross-Sectional (n=2,373)
Structured PICO
Is major depressive disorder associated with lower heart rate variability compared to healthy controls?
P
Population
2,373 adults (mean age 41.8 years, 66.8% female) including 524 healthy controls, 774 with remitted MDD, and 1,075 with current MDD.
E
Exposure
Major depressive disorder (current or remitted) and antidepressant use
C
Comparator
Healthy controls
O
Outcome
Standard deviation of normal-to-normal beats (SDNN) and cardiac vagal control, as indexed by respiratory sinus arrhythmia (RSA), measured during 1.5 hours of ambulatory electrocardiogram recordingsurrogate
The association between depression and lowered heart rate variability appears to be primarily driven by the use of antidepressants rather than the psychiatric condition itself.
Main Result
Effect estimate: effect size 0.125-0.269
p-value: P<=0.02 for SDNN; P<0.001 for RSA
Abstract
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(1/2) 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 < or = .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.