Key result
Major depressive disorder linked to ~65% higher risk of incident cardiometabolic disease over 15 years.
Why the study?
Major depressive disorder and specific depressive symptom profiles associated with inflammation may carry distinct cardiometabolic risk, but their differential associations with cardiometabolic disease incidence are unclear.
Does major depressive disorder and its specific symptom profiles increase the incidence of cardiometabolic disease in individuals without baseline cardiometabolic disease?
Cohort (n=1,858)
Does major depressive disorder and its specific symptom profiles increase the incidence of cardiometabolic disease in individuals without baseline cardiometabolic disease?
Hazard Ratio: 1.65 (95% CI 1.3–2.11)
Major depressive disorder is associated with a significantly increased risk of incident cardiometabolic disease over 15 years, driven by a general depression burden rather than specific symptom profiles.
Highlights CMD risk monitoring in MDD; extends prior associations but remains hypothesis-generating without RCTs.
INTRODUCTION: Major depressive disorder (MDD) has been linked to increased incidence of cardiometabolic disease (CMD). Depressive symptom profiles associated with inflammation (atypical energy-related symptoms (AES), anhedonia) may carry specific cardiometabolic risk. We investigated whether MDD, AES and anhedonia are associated with higher CMD incidence compared to typical depressive symptoms and control participants. METHODS: Data were from the Netherlands Study of Depression and Anxiety (NESDA), including participants with lifetime MDD and non-depressed controls, without baseline CMD (N = 1858). CMD incidence was established over 15-year follow-up using self-report, medication use, and glucose. AES, anhedonia, typical symptoms, and depression severity were derived from the Inventory of Depressive Symptomatology Self-Report. Cox proportional hazard models were adjusted for sociodemographic and lifestyle factors. RESULTS: CMD incidence rate was 21.3/1000 person years. MDD was associated with increased CMD incidence compared to controls (HR = 1.65, 95%CI: 1.30-2.11). In continuous analyses, only AES and depression severity were significantly associated with CMD incidence, though effect sizes were comparable across symptom profiles. When divided into severity tertiles and compared to controls, associations were largely similar across profiles, with no clear dose-response pattern. All profiles were associated with cardiovascular disease incidence, but only AES was associated with diabetes incidence. DISCUSSION: MDD is associated with CMD incidence over 15 years. Depressive symptom profiles did not show differential associations with CMD incidence. Effect sizes across profiles were comparable, suggesting a general rather than symptom-specific depression burden on cardiometabolic health risk. Continued monitoring of cardiometabolic risk factors is warranted for people with a history of depression.
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Zwiep et al. (2026) conducted a cohort in Major depressive disorder (n=1,858). Major depressive disorder vs. Non-depressed controls was evaluated on Cardiometabolic disease incidence (HR 1.65, 95% CI 1.30-2.11). Major depressive disorder was associated with an increased incidence of cardiometabolic disease over 15 years compared to non-depressed controls (HR 1.65; 95% CI 1.30-2.11).
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