Depression, anxiety and 6-year risk of cardiovascular disease.

OBJECTIVE: Depression and anxiety are considered etiological factors in cardiovascular disease (CVD), though their relative contribution and differentiation by clinical characteristics have not been studied intensively. We examined 6-year associations between depressive and anxiety disorders, clinical characteristics and newly-developed CVD. METHODS: DSM-IV diagnoses were established in 2510 CVD-free participants of the Netherlands Study of Depression and Anxiety. Data on subtype, severity, and psychoactive medication were collected. The 6-year incidence of CVD was assessed using Cox regression analyses adjusted for sociodemographic, health and lifestyle factors. RESULTS: One-hundred-six subjects (4.2%) developed CVD. Having both current depressive and anxiety disorders (HR=2.86, 95%CI 1.49-5.49) or current depression only (HR=2.30; 95%CI 1.10-4.80) was significantly associated with increased CVD incidence, whereas current anxiety only (HR=1.48; 95%CI 0.74-2.96) and remitted disorders (HR=1.48; 95%CI 0.80-2.75) were not associated. Symptom severity was associated with increased CVD onset (e.g., Inventory of Depressive Symptomatology per SD increase: HR=1.51; 95%CI 1.25-1.83). Benzodiazepine use was associated with additional CVD risk (HR=1.95; 95%CI 1.16-3.31). CONCLUSIONS: Current depressive (but not anxiety) disorder independently contributed to CVD in our sample of initially CVD-free participants. CVD incidence over 6years of follow-up was particularly increased in subjects with more symptoms, and in those using benzodiazepines.

Common mental disorders associated with 2-year diabetes incidence: the Netherlands Study of Depression and Anxiety (NESDA).

BACKGROUND: Few prospective cohort studies describe the risk of type 2 diabetes mellitus associated with depression or anxiety. The aim of this study was to determine the 2-year diabetes incidence and pattern of explanatory factors associated with depressive and/or anxiety disorders. METHODS: A prospective cohort of 2981 participants (aged 18-65 years, 66% women) recruited in the Netherlands Study of Depression and Anxiety (NESDA) from community, primary care and outpatient psychiatric clinics were followed-up for two years. Complete data were analyzed from 2460 participants without baseline diabetes. Lifetime or current (past 6-month) depressive and/or anxiety disorders at baseline were assessed using the Composite Interview Diagnostic Instrument (CIDI) and classified by the DSM-IV. Diabetes was classified by either self-report, medications, or fasting plasma glucose ≥ 7.0 mmol/L. Baseline covariates included age, gender, lifestyle factors, and medical conditions. Odds ratios (OR [95% confidence intervals]) for diabetes were determined using exact logistic regression. RESULTS: The unadjusted 2-year diabetes incidence was 0.2% (1/571), 1.1% (6/548), and 1.8% (24/1340) for no, remitted, and current depressive and/or anxiety disorders, respectively. In comparison to those without psychopathology, current depressive and/or anxiety disorders was associated with diabetes incidence in unadjusted (OR 10.4 [1.7, 429.0]) and age-adjusted (OR 11.9 (1.9, 423.0]) analyses. The strength of this association (beta coefficient) was slightly changed after further adjustments for impaired fasting glucose (11.4%), high triglycerides (-7.8%), and lifestyle cumulative risk score (-5.0%), in contrast to other covariates when assessed in separate models. LIMITATIONS: The low incidence of diabetes resulted in considerable uncertainty for the odds ratios and low statistical power that limited covariate adjustments. CONCLUSIONS: The relative odds of developing diabetes within two years was increased for persons with current depressive and/or anxiety disorders, which was partially explained by, but remained independent of, lifestyle cumulative risk factors.

Chronic medical conditions mediate the association between depression and cardiovascular disease mortality.

PURPOSE: To determine whether chronic medical conditions mediate the association between depression and cardiovascular disease (CVD) mortality. METHODS: Data analyzed were from 6,394 subjects aged 25-74 years who participated in extensive health examinations in the NHEFS conducted between 1971 and 1975 and follow-up studies to 1992. CVD mortality was the endpoint. Depression predictors were clinically significant depressive symptoms at baseline by the GWB-D, and/or at 1982-1984 by the CES-D ('baseline', 'new', or 'twice' depression). Chronic conditions were prevalent/incident high blood pressure, diabetes, and non-fatal CVD by examination and/or self-report. Mediation effects were assessed by stepwise adjustments of covariates and additive interactions in competing risks regression models (accounting for other mortality causes) and logit models. RESULTS: Baseline, new, and twice depression were significant predictors of CVD mortality in competing-risks models adjusted for demographics (HRs 1.3, 1.4, and 2.0), but effects were progressively weakened and became non-significant after adjustment for lifestyle factors, prevalent and incident medical conditions, respectively. CVD mortality risk was 80% higher for depression plus incident non-fatal CVD than without (HR 4.0 vs. 3.2, additive interaction), and mediation effects of depression via chronic medical conditions (particularly via incident non-fatal CVD) increased the risk by 2-11% in logit models, independent of all covariates. CONCLUSIONS: Several levels of evidence suggest that the association between depression and CVD mortality is partially mediated by prevalent/incident chronic medical conditions, as well as unhealthy lifestyle behaviors. Patients presenting with clinically significant depressive symptoms, particularly if persistent, should be assessed for both chronic conditions and lifestyle risk factors.

The impact of childhood abuse and recent stress on serum brain-derived neurotrophic factor and the moderating role of BDNF Val66Met.

RATIONALE: Recent findings show lowered brain-derived neurotrophic factor (BDNF) levels in major depressive disorder (MDD). Exposure to stressful life events may (partly) underlie these BDNF reductions, but little is known about the effects of early or recent life stress on BDNF levels. Moreover, the effects of stressful events on BDNF levels may in part be conditional upon a common variant on the BDNF gene (Val(66)Met; RS6265), with the Met allele being associated with a decrease in activity-dependent secretion of BDNF compared to the Val allele. METHODS: We investigated cross-sectionally in 1,435 individuals with lifetime MDD the impact of childhood abuse (CA) and recent life events on serum BDNF levels and assessed whether the impact of these events was moderated by the BDNF Val(66)Met polymorphism. RESULTS: Overall, BDNF Met carriers had reduced serum BDNF levels when exposed to CA in a dose-dependent way. Moreover, exposure to recent life events was also associated with decreases in BDNF levels, but this was independent of BDNF Val(66)Met. Moreover, when not exposed to CA, Met carriers had higher BDNF levels than the Val/Val individuals, who did not show decreases in BDNF associated with CA. Finally, these findings were only apparent in the MDD group without comorbid anxiety. CONCLUSIONS: These gene-environment interactions on serum BDNF levels suggest that Met carriers are particularly sensitive to (early) stressful life events, which extends previous findings on the moderating role of the BDNF Val(66)Met polymorphism in the face of stressful life events.