Association between Anxiety Disorders and Heart Rate Variability in The Netherlands Study of Depression and Anxiety (NESDA)

Objective: To determine whether patients with different types of anxiety disorder (panic disorder, social phobia, generalized anxiety disorder) have higher heart rate and lower heart rate variability compared with healthy controls in a sample that was sufficiently powered to examine the confounding effects of lifestyle and antidepressants. Methods: The standard deviation of the normal-to-normal intervals (SDNN), heart rate (HR), and respiratory sinus arrhythmia (RSA) were measured in 2059 subjects (mean age = 41.7 years, 66.8% female) participating in The Netherlands Study of Depression and Anxiety (NESDA). Based on the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) and Composite International Diagnostic Interview (CIDI), NESDA participants were classified as healthy controls (n = 616), subjects with an anxiety diagnosis earlier in life (n = 420), and subjects with current anxiety diagnosis (n = 1059). Results: Current anxious subjects had a significantly lower SDNN and RSA compared with controls. RSA was also significantly lower in remitted anxious subjects compared with controls. These associations were similar across the three different types of anxiety disorders. Adjustment for lifestyle had little impact. However, additional adjustment for antidepressant use reduced all significant associations between anxiety and HRV to nonsignificant. Anxious subjects who used a tricyclic antidepressant, a selective serotonin reuptake inhibitor, or another antidepressant showed significantly lower mean SDNN and RSA compared with controls (effect sizes = 0.20–0.80 for SDNN and 0.42–0.79 for RSA). Nonmedicated anxious subjects did not differ from controls in mean SDNN and RSA. Conclusion: This study shows that anxiety disorders are associated with significantly lower HR variability, but the association seems to be driven by the effects of antidepressants. ANOVA = analysis of variance; ANS = autonomic nervous system; ATC = anatomical therapeutic chemical; BAI = Beck Anxiety Inventory; BMI = body mass index; CIDI = Composite International Diagnostic Interview; CVD = cardiovascular disease; dZ = changes in thorax impedance; ECG = electrocardiogram; GAD = generalized anxiety disorder; HR = heart rate; HRV = heart rate variability; IBI = inter-beat-interval; MDD = major depressive disorder; MET = multiple of one's resting metabolic rate times minutes of physical activity; NESDA = The Netherlands Study of Depression and Anxiety; PD = panic disorder; pv = peak-valley; PNS = parasympathetic nervous system; RR = respiratory rate; RSA = respiratory sinus arrhythmia; SDNN = standard deviation of the normal-to-normal interval; SNS = sympathetic nervous system; SP = social phobia; VU-AMS = Vrije Universiteit Ambulatory Monitoring System; SSRI = selective serotonin reuptake inhibitor; TCA = tricyclic antidepressant.