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.

The Netherlands Study of Depression and Anxiety (NESDA) is a multi-site naturalistic cohort study to: (1) describe the long-term course and consequences of depressive and anxiety disorders, and (2) to integrate biological and psychosocial research paradigms within an epidemiological approach in order to examine (interaction between) predictors of the long-term course and consequences. Its design is an eight-year longitudinal cohort study among 2981 participants aged 18 through 65 years. The sample consists of 1701 persons with a current (six-month recency) diagnosis of depression and/or anxiety disorder, 907 persons with life-time diagnoses or at risk because of a family history or subthreshold depressive or anxiety symptoms, and 373 healthy controls. Recruitment took place in the general population, in general practices (through a three-stage screening procedure), and in mental health organizations in order to recruit persons reflecting various settings and developmental stages of psychopathology. During a four-hour baseline assessment including written questionnaires, interviews, a medical examination, a cognitive computer task and collection of blood and saliva samples, extensive information was gathered about key (mental) health outcomes and demographic, psychosocial, clinical, biological and genetic determinants. Detailed assessments will be repeated after one, two, four and eight years of follow-up. The findings of NESDA are expected to provide more detailed insight into (predictors of) the long-term course of depressive and anxiety disorders in adults. Besides its scientific relevance, this may contribute to more effective prevention and treatment of depressive and anxiety disorders. Copyright © 2008 John Wiley & Sons, Ltd.

The present study compared blood pressure levels between subjects with clinical anxiety and depressive disorders with healthy controls. Cross-sectional data were obtained in a large cohort study, the Netherlands Study of Depression and Anxiety (N=2981). Participants were classified as controls (N=590) or currently or remittedly depressed or anxious subjects (N=2028), of which 1384 were not and 644 were using antidepressants. Regression analyses calculated the contributions of anxiety and depressive disorders and antidepressant use to diastolic and systolic blood pressures, after controlling for multiple covariates. Heart rate and heart rate variability measures were subsequently added to test whether effects of anxiety/depression or medication were mediated by vagal control over the heart. Higher mean diastolic blood pressure was found among the current anxious subjects (β=0.932; P=0.03), although anxiety was not significantly related to hypertension risk. Remitted and current depressed subjects had a lower mean systolic blood pressure (β=−1.74, P=0.04 and β=−2.35, P=0.004, respectively) and were significantly less likely to have isolated systolic hypertension than controls. Users of tricyclic antidepressants had higher mean systolic and diastolic blood pressures and were more likely to have hypertension stage 1 (odds ratio: 1.90; 95% CI: 0.94 to 3.84; P=0.07) and stage 2 (odds ratio: 3.19; 95% CI: 1.35 to 7.59; P=0.008). Users of noradrenergic and serotonergic working antidepressants were more likely to have hypertension stage 1. This study shows that depressive disorder is associated with low systolic blood pressure and less hypertension, whereas the use of certain antidepressants is associated with both high diastolic and systolic blood pressures and hypertension.

Context: Stress is suggested to lead to metabolic dysregulations as clustered in the metabolic syndrome, but the underlying biological mechanisms are not yet well understood.Objective: We examined the relationship between two main str systems, the autonomic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis, with the metabolic syndrome and its components.Design: The design was baseline data (yr 2004–2007) of a prospective cohort: the Netherlands Study of Depression and Anxiety (NESDA).Setting: The study comprised general community, primary care, and specialized mental health care.Participants: This study included 1883 participants aged 18–65 yr.Main Outcome Measures: Autonomic nervous system measures included heart rate, respiratory sinus arrhythmia (RSA; high RSA reflecting high parasympathetic activity), and preejection period (PEP; high PEP reflecting low sympathetic activity). HPA axis measures included the cortisol awakening response, evening cortisol, and a 0.5 mg dexamethasone suppression test as measured in saliva. Metabolic syndrome was based on the updated Adult Treatment Panel III criteria and included high waist circumference, serum triglycerides, blood pressure, serum glucose, and low high-density lipoprotein cholesterol.Results: RSA and PEP were both independently negatively associated with the presence of the metabolic syndrome, the number of metabolic dysregulations as well as all individual components except high-density lipoprotein cholesterol (all P < 0.02). Heart rate was positively related to the metabolic syndrome, the number of metabolic dysregulations, and all individual components (all P < 0.001). HPA axis measures were not related to metabolic syndrome or its components.Conclusion: Our findings suggest that increased sympathetic and decreased parasympathetic nervous system activity is associated with metabolic syndrome, whereas HPA axis activity is not.

Background
Dyslipidemia and obesity have been observed in persons with severe anxiety or depression, and in tricyclic antidepressant (TCA) users. This likely contributes to the higher risk of cardiovascular disease (CVD) in anxiety and depressive disorders. We aimed to elucidate whether biological stress systems or lifestyle factors underlie these associations. If so, they may be useful targets for CVD prevention and intervention.
Methods
Within 2850 Netherlands Study of Depression and Anxiety (NESDA) participants, we evaluated the explaining impact of biological stress systems (i.e., the hypothalamic–pituitary–adrenal [HPA] axis, autonomic nervous system [ANS] and inflammation) and lifestyle factors (i.e., tobacco and alcohol use, and physical activity) on adverse associations of anxiety and depression severity and TCA use with high and low-density lipoprotein cholesterol, triglycerides, body mass index and waist circumference. Through linear regression analyses, percentual change (%Δ) in β was determined and considered significant when %Δ>10.
Results
The inflammatory marker C-reactive protein had the most consistent impact (explaining 14–53% of the associations of anxiety and depression severity and TCA use with lipid and obesity levels), followed by tobacco use (explaining 34–43% of the associations with lipids). The ANS mediated all associations with TCA use (explaining 32–61%). The HPA axis measures did not explain any of the associations.
Conclusions
Increased dyslipidemia and (abdominal) obesity risk in patients with more severe anxiety disorders and depression may be partly explained by chronic low-grade inflammation and smoking. TCAs may increase metabolic risk through enhanced sympathetic and decreased parasympathetic ANS activity. That the HPA axis had no impact in our sample may reflect the possibility that the HPA axis only plays a role in acute stress situations rather than under basal conditions.