Background: Depression is a primary public health challenge that affects individuals of all ages. This study aims to reveal information on spatial and temporal changes in depression by describing temporal trend differences, regional differences, and gender differences. Materials and Methods: Utilizing data from the Global Burden of Disease Study 2021 (GBD2021) from 1990 to 2021, we outlined the prevalence and burden of depression among 204 countries in 21 regions, including age and sex disparities, and explored the correlation between depressive burden and the sociodemographic index (SDI). The age-standardized rates of prevalence (ASPR), disability-adjusted life years (DALYs, age-standardized DALY rate, ASDR), and estimated annual percentage change (EAPC) were employed to evaluate the global burden of depression. Results: Our study revealed a greater than 1.8-fold increase in prevalent cases and DALYs for global depressive disorder from 1990 to 2021. Globally, the age-standardized rates (ASRs) slightly declined, with a 1.32% decrease in the ASPR and a 1.84% decrease in the ASDR from 1990 to 2019. The main decline occurred from 2005 to 2010 (4.86% decrease in the ASPR and 6.09% decrease in the ASDR), with the majority of the contributions occurring in the low-middle-SDI and low-SDI regions. The global ASPR and ASDR experienced astonishing jumps from 2019 to 2021, resulting in increases of nearly 11% in the ASPR and 13% in the ASDR. Notably, the ASPR and ASDR of depression decreased in females but increased in males from 1990 to 2019 and reversed thereafter. From 1990 to 2021, among the 21 regions, the EAPCs in most regions were >0, with the only exceptional decline occurring in East Asia in the ASPR -0.06 [95% Cl:-0.10 to -0.03]) and ASDR -0.09 [95% Cl:-0.13 to -0.05]). Compared with those in other regions, the ASPR (0.42 [95% Cl: 0.34-0.49]) and ASDR (0.53 [95% Cl: 0.46-0.61]) were greater in high-income North America. Among the five SDI regions, the largest increases in ASPR (0.25 [95% Cl: 0.21-0.30]) and ASDR (0.31 [95% Cl: 0.26-0.37]) occurred in the high-SDI region, with the majority of the contributions occurring from 2019 to 2021. Worldwide, a decreasing trend and significant associations between the ASPR and the SDI (R = -0.22, p=0.0013) and between the ASDR and the SDI (R = -0.28, p < 0.001) were observed. Conclusion: Depression remains a serious challenge worldwide. The trends in depression burden varied across regions and groups. A vibrant socioeconomic environment could have a positive impact on the disease burden. Mental health should be incorporated into public health preparedness and emergency plans in practical ways on the basis of the national conditions of each country.

#	Concept	H-Index	Publications	Citations
1	Medicine	1	1	23
2	Immunology	1	1	23
3	Neurology	1	1	23
4	Neuroscience	1	1	23
5	Cell Signaling	1	1	23

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