Divergent Trends Between Zinc Deficiency and Depressive Disorders, 1990–2021: A Global GBD Analysis

Background Despite biological plausibility linking zinc deficiency to depression, population-level evidence remains inconsistent. This study examined global trends and associations between zinc deficiency(ZD) and depressive disorders(DD) over three decades.
Methods Using GBD 2021 age-standardized DALY rates for 204 countries/territories, we summarized global and SDI-quintile trends and evaluated 2021 cross-sectional correlations, year-to-year associations (1990–2021), cross-correlations in growth-rate and detrended-residual series, spatial autocorrelation/lag diagnostics, and multilevel modeling with socioeconomic adjustment.
Results Globally, ZD burden declined by 91.66% (17.59→1.47 per 100,000), whereas DD burden increased by 12.03% (675.27→756.50). The 2021 country-level correlation was small (r=0.154, 95%CI 0.015–0.288; P=0.030) and within-quintile tests were non-significant after multiplicity correction. Year-to-year and cross-correlation signals were directionally inconsistent across preprocessing choices. Residual spatial dependence persisted after SDI adjustment, but SAR/SEM/SDM models did not change the direction or significance of the ZD→DD association.
Conclusions The dramatic reduction in ZD has not translated into decreased DD burden at ecological level. Findings argue against a single-nutrient pathway as a lever for population mental health, underscoring the need for individual-level, mechanistic, and implementation-focused research.

Keywords：Global Burden of Disease; Zinc deficiency; Depressive Disorders; Disability-adjusted life years (DALY); Nutritional psychiatry; Socio-demographic index (SDI)