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)研究背景：尽管锌缺乏与抑郁之间的关联具备生物学合理性，但人群层面的相关证据仍存在分歧。本研究针对三十年间全球范围内锌缺乏（zinc deficiency, ZD）与抑郁障碍（depressive disorders, DD）的流行趋势及二者关联展开分析。 研究方法：本研究采用2021年全球疾病负担（Global Burden of Disease, GBD）报告中204个国家/地区的年龄标化伤残调整生命年（Disability-adjusted life years, DALY）率，对全球及社会人口指数（Socio-demographic index, SDI）五分位组的流行趋势进行总结，并针对以下内容展开评估：2021年横断面相关性、1990-2021年的年度关联、增长率与去趋势残差序列的互相关、空间自相关/滞后诊断，以及经社会经济学因素校正的多水平模型。 研究结果：全球范围内，锌缺乏的疾病负担下降了91.66%（从每10万人17.59降至1.47），而抑郁障碍的疾病负担则上升了12.03%（从675.27升至756.50）。2021年国家层面的相关性较弱（r=0.154，95%置信区间[95%CI] 0.015~0.288；P=0.030），且经多重比较校正后，五分位组内的检验结果无统计学意义。不同预处理方式下，年度关联与互相关的信号方向不一致。经社会人口指数校正后，仍存在残余空间自相关性，但空间自回归模型（Spatial Autoregressive Model, SAR）、空间误差模型（Spatial Error Model, SEM）与空间杜宾模型（Spatial Durbin Model, SDM）均未改变锌缺乏与抑郁障碍关联的方向与统计学显著性。 研究结论：人群层面锌缺乏的显著降低并未转化为生态层面抑郁障碍疾病负担的下降。本研究结果不支持单一营养通路可作为改善人群精神健康的干预靶点，强调了开展个体层面、机制导向及聚焦实施策略的相关研究的必要性。 关键词：全球疾病负担（Global Burden of Disease）；锌缺乏（Zinc deficiency）；抑郁障碍（Depressive Disorders）；伤残调整生命年（Disability-adjusted life years, DALY）；营养精神病学（Nutritional psychiatry）；社会人口指数（Socio-demographic index, SDI）