title: Association between major depressive disorder and heart rate variability in the Netherlands Study of Depression and Anxiety (NESDA).
abstract: BACKGROUND
  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.
  
  
  METHODS
  Cross-sectional analyses from a large depression cohort study.
  
  
  METHODS
  The Netherlands Study of Depression and Anxiety.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Carmilla M M
authors.initials: CM
authors.lastname: Licht
authors.forename: Eco J C
authors.initials: EJ
authors.lastname: de Geus
authors.forename: Frans G
authors.initials: FG
authors.lastname: Zitman
authors.forename: Witte J G
authors.initials: WJ
authors.lastname: Hoogendijk
authors.forename: Richard
authors.initials: R
authors.lastname: van Dyck
authors.forename: Brenda W J H
authors.initials: BW
authors.lastname: Penninx
mesh_terms: D000328:Adult; D001145:Arrhythmias, Cardiac / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology*; D015897:Comorbidity; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000453:epidemiology* / Q000523:psychology*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004562:Electrocardiography; D005260:Female; D006304:Health Status; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008297:Male; D009068:Movement; D012119:Respiration; D012146:Rest; D011795:Surveys and Questionnaires