Increased metabolic variability is associated with newly diagnosed depression: A nationwide cohort study

The effect of dynamic changes in metabolic parameters over time on the development of depression has yet to be examined. In this study, we aimed to determine the association between the variability of metabolic parameters and the development of depression using nationally representative data.

We used health examination data provided by the South Korean National Health Insurance System (NHIS) and included those who underwent the examination ≥ 3 times within five years of enrollment, without a previous history of depression (n = 9,058,424). The variability of each metabolic parameter including weight circumference, blood pressure, fasting blood glucose, high-density lipoprotein cholesterol, and triglyceride levels was estimated using variability independent of mean (VIM) indices. High variability was defined as the highest quartile (Q4) of variability.

Each metabolic parameter with high variability was associated with a higher risk of newly diagnosed depression compared to those with low variability, after adjusting for age, sex, smoking, alcohol drinking, regular exercise, income status, baseline diabetes, hypertension, and dyslipidemia. As the number of highly variable metabolic parameters increased, the risk for newly diagnosed depression increased even after adjusting for the aforementioned covariates (hazard ratio (HR) = 1.4, 95% confidence interval (CI): 1.3 - 1.4 in those with five highly variable parameters compared to those with no highly variable parameter).

relatively short observation period; no systematic measure of depression severity.

Our results suggest that the variability of metabolic parameters is an independent risk factor for depression.