Global Burden of Mental Disorders in Women of Reproductive Age from 1990 to 2021: A Comprehensive Analysis and Trend Prediction of Depression, Anxiety, Bipolar Disorder, and Schizophrenia

Global Burden of Mental Disorders in Women of Reproductive Age from 1990 to 2021: A Comprehensive Analysis and Trend Prediction of Depression, Anxiety, Bipolar Disorder, and Schizophrenia | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Global Burden of Mental Disorders in Women of Reproductive Age from 1990 to 2021: A Comprehensive Analysis and Trend Prediction of Depression, Anxiety, Bipolar Disorder, and Schizophrenia Junyao Li, Bo Song, Min Cai, Wanqi Sun, Luping Wang, Shichang Yang, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6678574/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background： Mental disorders are a significant global health concern recognized by the World Health Organization (WHO). They contribute substantially to the disease burden and are strongly associated with high suicide rates.Depression, anxiety, bipolar disorder, and schizophrenia are among the most prevalent mental illnesses, severely affecting cognitive function, emotional regulation, and social interaction.Women of reproductive age (15–49 years) encounter distinct physiological and psychological challenges, rendering them more susceptible to stress. This heightened vulnerability elevates their risk of pregnancy-related complications, maternal and infant health issues, and neurodegenerative diseases.Furthermore, socioeconomic stress, gender role expectations, reproductive factors, and restricted access to healthcare collectively exacerbate their vulnerability to mental disorders.However, comprehensive evaluations of the long-term mental health burden in this population remain scarce. Aims： This study aims to quantify the global disease burden of depression, anxiety, bipolar disorder, and schizophrenia in women of reproductive age from 1990 to 2021, using GBD 2021 data. It will analyze their spatiotemporal distribution, assess the impact of the Sociodemographic Index (SDI) on disease burden, and provide evidence to support the development of targeted prevention and control strategies. Methods： Bayesian meta-regression was applied to calculate age-standardized rates (ASIR) and Disability-Adjusted Life Years (DALYs) using GBD 2021 standardized data.The data were stratified based on GBD standards into 7 age subgroups (15–49 years), 21 geographical regions, and 5 SDI levels.The Joinpoint regression model was used to estimate the annual percent change (EAPC, 95% UI).Statistical analysis was performed using R software. Results： From 1990 to 2021, depression and anxiety in women of reproductive age showed a continuous global increase.Anxiety-related DALYs rose from 9.3 million (95% UI: 5.9–13.6) to 16.4 million (95% UI: 10.4–24.0, EAPC = 0.16).In high-income regions, such as North America (EAPC = 0.64), the age-standardized death rate (ASDR) for depression rose from 948.86/100,000 to 1,073.5/100,000.The ASDR for bipolar disorder remained stable, while schizophrenia showed a slight negative trend (EAPC = -0.02).High SDI regions displayed a polarized burden of anxiety and depression, with North America having the highest depression ASDR at 1,929.21/100,000, while low SDI regions saw a significant increase in schizophrenia-related DALYs.Age-stratified analysis revealed that the burden of bipolar disorder was highest in the 15–19 age group, schizophrenia in the 20–24 age group, and depression and anxiety in the 25–34 age group. Conclusions： Depression and anxiety are the primary mental health threats for women of reproductive age, with a particularly pronounced disease polarization effect in high-income regions.Therefore, targeted interventions are urgently needed to reduce socioeconomic disparities, improve perinatal mental health services, and prioritize resource allocation to conflict-affected and low SDI regions.Policymakers should integrate mental health into maternal healthcare systems and use digital tools to reduce the risk of long-term disability. Women of reproductive age Mental disorders Disease burden Incidence rate DALYs Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Introduction According to the 2019 Global Burden of Disease (GBD 2019) study published in The Lancet Psychiatry, mental disorders rank among the top ten contributors to the global disease burden, with disability rates among the top three. They account for 4.9% of global DALYs, and their burden has shown a significant upward trend since 1990 [ 1 , 2 ] .Mental disorders exhibit a distinct early-onset and chronic progression pattern, affecting approximately 970 million people worldwide. Among them, more than 380 million suffer from depression, and 301 million experience anxiety disorders [ 3 , 4 ] . Additionally, 50% of patients experience their first onset before the age of 24 [ 5 ] .Cognitive impairment and emotional dysregulation caused by mental disorders not only reduce occupational functioning and weaken social relationships but also impose a substantial economic burden [ 6 ] . From an economic perspective, the cost structure of mental disorders is characterized by "low direct medical expenditures and high hidden social losses."For example, the annual direct medical costs for patients with depression range from $ 1,200 to $ 4,500, while for those with severe mental disorders requiring long-term hospitalization, the annual costs can reach $ 10,000 to $ 60,000 [ 1 ] .However, due to a global treatment gap of 50%, direct medical expenditures account for only 37% of the total burden [ 7 ] .More critically, anxiety disorder patients experience a 28% reduction in annual income due to decreased work efficiency, while schizophrenia patients face a lifetime income loss of up to $ 1.23 million [ 8 ] .Additionally, depression patients have an increased risk of cardiovascular comorbidities [ 9 ] , leading to higher medical costs, which together create a dual economic burden of productivity loss and comorbidity-related expenses. Notably, women of reproductive age are at high risk for mental disorders due to a combination of biological and social vulnerabilities.For example, 40% of Chinese women experience depressive states during pregnancy [ 10 ] , and globally, the years lived with disability (YLDs) due to depression are significantly higher in women of reproductive age than in men [ 11 ] .Moreover, endogenous hormone levels (such as estradiol) not only influence emotional stability and mental health in women of reproductive age but may also increase the risk of cognitive decline and neurodegenerative diseases after menopause [ 12 ] .Studies indicate that hormonal fluctuations increase the risk of perinatal depression [ 13 ] , and public health emergencies may further exacerbate this risk [ 14 ] .Since the outbreak of COVID-19 in late 2019, global prevalence rates of anxiety and depression have risen significantly. The World Health Organization (WHO) reported that the pandemic led to a 25% increase in global anxiety and depression prevalence [ 15 ] .Young people and women have been the most severely affected, and pregnant women, as a particularly vulnerable group, are especially prone to anxiety and depression during the pandemic.Depression and anxiety have a high comorbidity rate among women of reproductive age, with potential mutual influence and conversion between the two disorders [ 16 ] .Social role conflicts may further contribute to the higher prevalence of anxiety disorders in women compared to men.Meanwhile, the global 50% treatment gap and the stigma surrounding mental illness further exacerbate the challenges faced by women of reproductive age [ 17 ] .Studies show that 75% of women with mental disorders do not receive standardized treatment [ 18 ] , which not only increases the risk of cognitive decline in menopause but also reinforces the negative interaction chain of "biological susceptibility–social stress–economic deprivation."Therefore, a systematic analysis of the evolution of the mental disorder burden among women of reproductive age from 1990 to 2019 is crucial for breaking this interaction chain. Unlike traditional epidemiological studies, the GBD database employs a globally standardized Bayesian mixed-effects model, integrating multi-source heterogeneous data while systematically correcting for diagnostic inconsistencies and underreporting biases. This enables spatiotemporal comparability in disease incidence estimates [ 19 ] .Based on GBD 2021 data, this study systematically analyzes the burden of mental disorders among women of reproductive age worldwide and quantifies the disparities in disease burden across different regions and populations. The findings provide scientific evidence for precision prevention strategies and adaptive health policies. Methods Data source The 2021 GBD estimated the incidence and DALYs of mental disorders in 204 countries and regions from 1990 to 2021.This study focuses on the incidence and disability trends of depression, anxiety disorders, bipolar disorder, and schizophrenia in women of reproductive age worldwide from 1990 to 2021.Additionally, we analyzed age-group differences within this population, categorizing them into seven subgroups: 15–20, 21–25, 26–30, 31–35, 36–40, 41–45, and 46–49 years. Data on the incidence and DALYs of depression, anxiety disorders, bipolar disorder, and schizophrenia in specific populations were obtained from the publicly available Institute for Health Metrics and Evaluation (IHME) online tool ( https://vizhub.healthdata.org/gbd-results/ ) [ 20 ] .Data coding follows the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), or the International Classification of Diseases, Eleventh Revision (ICD-11), and is based on confirmed cases of depression, anxiety disorders, bipolar disorder, and schizophrenia.The ASIR and ASDR of these mental health conditions were analyzed by region, country, age, and year. Population data for women of reproductive age were obtained from the World Population Prospects 2019 ( https://www.un.org/zh/desa/world-population-prospects-2019 ), a report by the United Nations Department of Economic and Social Affairs, Population Division, providing official estimates and projections [ 21 ] . Statistical analysis A descriptive analysis of cases per 100,000 people worldwide, stratified by age group, was conducted to assess the burden of depression, anxiety disorders, bipolar disorder, and schizophrenia among women of reproductive age. The results were reported with a 95% UI, derived from 1,000 posterior distribution samples per variable, using the 2.5th and 97.5th percentiles of the uncertainty distribution. The EAPC was used to assess disease burden trends from 1990 to 2021 and estimate the disease burden in 2021 [ 22 ] . The ASDR for each study year was collected, with the calendar year used as a regression factor. A regression model was fitted to the natural logarithm of these rates, yielding the equation: ln(rate) = α + β * calendar year, where β represents the EAPC.The EAPC and its 95% confidence interval (CI) were calculated using the equation: EAPC = 100 * (e^β − 1).Additionally, ASIR and ASDR data for depression, anxiety disorders, bipolar disorder, and schizophrenia were analyzed using the same methods. All statistical analyses were conducted in R software ( https://www.r-project.org/ ) with a significance level of 0.05. Results Incidence of Depression, Anxiety, Bipolar Disorder, and Schizophrenia Among Women of Reproductive Age Table 1 (Online Supplementary Table 1) summarizes key findings from the 2021 GBD study on the incidence and ASIR of depression, anxiety, bipolar disorder, and schizophrenia from 1990 to 2021 across the world, 21 regions, and five SDI groups.Globally, the number of depression cases among women of reproductive age increased from 77.72 million (95% UI: 58,860,491 to 102,539,344) in 1990 to 133 million (95% UI: 99,032,450 to 177,876,463) in 2021. However, the ASIR increased slightly from 5,898.5 per 100,000 population (95% UI: 4,486.52 to 7,740.66) to 6,808.01 per 100,000 (95% UI: 5,049.99 to 9,106.66), with an estimated annual percentage change (EAPC) of -0.18 (95% CI: -0.39 to 0.04).Significant regional variations were observed. In 2021, Australasia (10,269.64 per 100,000, 95% UI: 7,057.12 to 14,369.31), Central Sub-Saharan Africa (11,270.02 per 100,000, 95% UI: 7,523.17 to 16,274.56), and high-income North America (12,689.95 per 100,000, 95% UI: 9,828.58 to 16,139.08) reported the highest ASIRs.In contrast, the lowest ASIRs were recorded in East Asia (2,956.12 per 100,000, 95% UI: 2,227.57 to 3,840.52) and Western Sub-Saharan Africa (6,114.54 per 100,000, 95% UI: 4,369.47 to 8,446.05).Central America exhibited the fastest-growing ASIR (EAPC = 1.02, 95% CI: 0.80 to 1.24). In contrast, East Asia (EAPC = -1.40, 95% CI: -1.65 to -1.16), South Asia (EAPC = -0.99, 95% CI: -1.31 to -0.66), and low-SDI regions (EAPC = -0.36, 95% CI: -0.53 to -0.19) experienced significant declines. Globally, anxiety cases among women of reproductive age rose from 107 million (95% UI: 70,583,850 to 149,386,510) in 1990 to 190 million (95% UI: 126,600,290 to 262,953,960) in 2021. The ASIR increased from 797.81 per 100,000 (95% UI: 527.95 to 1,108.31) to 976.14 per 100,000 (95% UI: 650.09 to 1,355.11), with an EAPC of 0.24 (95% CI: 0.08 to 0.39).Tropical Latin America saw the largest increase in ASIR (EAPC = 1.08, 95% CI: 0.76 to 1.40), reaching 1,851.05 per 100,000 (95% UI: 1,223.06 to 2,604.60) in 2021. High-income North America (EAPC = 0.82, 95% CI: 0.47 to 1.16) and Central America (EAPC = 0.74, 95% CI: 0.53 to 0.95) also showed a rapid upward trend. In contrast, significant declines in ASIR occurred in East Asia (EAPC = -0.53, 95% CI: -0.69 to -0.37) and high-income Asia Pacific (EAPC = -0.16, 95% CI: -0.33 to 0.00). In 2021, the highest ASIRs were recorded in Tropical Latin America (1,851.05 per 100,000, 95% UI: 1,223.06 to 2,604.60) and high-income North America (1,576.93 per 100,000, 95% UI: 1,055.10 to 2,175.10). Globally, the number of bipolar disorder cases among women of reproductive age rose from 575,600 (95% UI: 344,082 to 875,035) in 1990 to 826,400 (95% UI: 484,408 to 1,270,443) in 2021. However, the ASIR showed only a modest increase from 41.64 per 100,000 (95% UI: 24.69 to 63.45) to 43.16 per 100,000 (95% UI: 25.43 to 66.23), with an EAPC of 0.09 (95% CI: 0.07 to 0.11).A slight increase in ASIR was observed in middle-SDI regions (EAPC = 0.26, 95% CI: 0.22 to 0.30) and high-income North America (EAPC = 0.06, 95% CI: 0.04 to 0.08), whereas Eastern Europe (EAPC = -0.01, 95% CI: -0.01 to -0.01) and East Asia (EAPC = -0.02, 95% CI: -0.03 to -0.01) saw slight decline.In 2021, the highest ASIRs were recorded in Tropical Latin America (95.70 per 100,000, 95% UI: 59.41 to 141.64) and Andean Latin America (76.95 per 100,000, 95% UI: 42.16 to 125.71). Globally, the number of schizophrenia cases among women of reproductive age rose from 378,300 (95% UI: 227,553 to 559,592) in 1990 to 513,300 (95% UI: 302,798 to 767,916) in 2021. However, the ASIR showed a slight decrease from 26.98 per 100,000 (95% UI: 16.19 to 40.01) to 26.71 per 100,000 (95% UI: 15.76 to 39.94), with an EAPC of -0.02 (95% CI: -0.03 to -0.01).A significant increase in ASIR was observed in Eastern Europe (EAPC = 0.19, 95% CI: 0.15 to 0.22) and high-income Asia Pacific (EAPC = 0.22, 95% CI: 0.15 to 0.29), while middle-SDI regions (EAPC = -0.09, 95% CI: -0.10 to -0.08) and Western Europe (EAPC = -0.04, 95% CI: -0.06 to -0.02) showed a downward trend.In 2021, the highest ASIRs were recorded in Eastern Europe (6,990.81 per 100,000, 95% UI: 4,956.63 to 9,586.01) and high-income North America (12,689.95 per 100,000, 95% UI: 9,828.58 to 16,139.08). The DALYs of depression, anxiety disorders, bipolar disorder, and schizophrenia in women of reproductive age Table 2 (Online supplementary table 2) presents the key GBD study results on DALYs and ASDR for depression, anxiety disorders, bipolar disorder, and schizophrenia from 1990 to 2021 across the globe, 21 regions, and 5 SDI groups. Between 1990 and 2021, the DALYs of depression among women of reproductive age globally increased from 12.445 million (95% UI: 8,084,219 to 18,023,437) to 21.042 million (95% UI: 13,468,194 to 30,593,481), while the ASDR rose from 948.86 per 100,000 (95% UI: 617.06 to 1,369.93) to 1,073.5 per 100,000 (95% UI: 686.73 to 1,562.48), with an EAPC of -0.14 (95% CI: -0.32 to 0.04).Significant regional differences were observed: high-income North America saw the largest increase in ASDR (EAPC = 0.64, 95% CI: 0.36 to 0.92), reaching 1,929.21 per 100,000 in 2021 (95% UI: 1,284.02 to 2,772.95), while East Asia experienced a significant decrease (EAPC = -1.15, 95% CI: -1.34 to -0.95), with an ASDR of 560.51 per 100,000 in 2021 (95% UI: 365.80 to 799.17). Sub-Saharan Africa (Central) had the highest ASDR in 2021 (1,695.20 per 100,000, 95% UI: 994.94 to 2,610.73), but the trend remained stable (EAPC=0.02, 95% CI: -0.07 to 0.12). The DALYs of anxiety disorders in women of reproductive age globally increased from 9.329 million (95% UI: 5,917,676 to 13,620,685) in 1990 to 16.448 million (95% UI: 10,383,333 to 24,009,992) in 2021. The ASDR rose from 698.30 per 100,000 (95% UI: 442.60 to 1,018.65) to 844.05 per 100,000 (95% UI: 532.79 to 1,232.57), with an EAPC of 0.16 (95% CI: 0.01 to 0.32).Tropical Latin America saw the largest increase in ASDR (EAPC = 1.40, 95% CI: 0.88 to 1.93), reaching 1,874.23 per 100,000 in 2021 (95% UI: 1,199.81 to 2,688.52). In contrast, the ASDR in East Asia declined (EAPC=-0.53, 95% CI: -0.70 to -0.37), decreasing to 616.80 per 100,000 in 2021 (95% UI: 390.72 to 913.98). Additionally, regions with higher ASDRs in 2021 include high-income North America at 1,414.22 per 100,000 (95% UI: 916.57 to 2,054.75), and Western Europe at 1,333.41 per 100,000 (95% UI: 827.15 to 1,967.63). The DALYs of bipolar disorder in women of reproductive age globally increased from 1.89 million (95% UI: 1,181,247 to 2,850,106) in 1990 to 2.807 million (95% UI: 1,740,129 to 4,226,051) in 2021. The ASDR slightly increased from 142.30 per 100,000 (95% UI: 88.88 to 214.07) to 143.77 per 100,000 (95% UI: 89.11 to 216.63), with an EAPC of 0.03 (95% CI: 0.02 to 0.04).In regions with moderate SDI, the ASDR slightly increased (EAPC=0.26, 95% CI: 0.24 to 0.28), reaching 138.24 per 100,000 in 2021 (95% UI: 85.78 to 208.03). In high-income North America, the ASDR declined (EAPC = -0.04, 95% CI: -0.05 to -0.03), reaching 197.04 per 100,000 in 2021 (95% UI: 128.19 to 283.58).In 2021, Tropical Latin America had the highest ASDR (368.90 per 100,000, 95% UI: 233.33 to 551.85), followed closely by Andean Latin America (281.66 per 100,000, 95% UI: 161.72 to 449.59), but both regions had EAPCs close to zero. The DALYs of schizophrenia in women of reproductive age globally increased from 3.115 million (95% UI: 2,138,675 to 4,238,277) in 1990 to 4.837 million (95% UI: 3,318,473 to 6,567,286) in 2021. The ASDR slightly decreased from 244.12 per 100,000 (95% UI: 168.33 to 329.91) to 243.46 per 100,000 (95% UI: 166.79 to 331.29), with an EAPC of 0.00 (95% CI: 0.00 to 0.01).The ASDR in Eastern Europe showed a significant increase (EAPC = 0.21, 95% CI: 0.17 to 0.26), reaching 193.92 per 100,000 in 2021 (95% UI: 130.80 to 265.36).In regions with a moderate SDI, the ASDR declined (EAPC = -0.02, 95% CI: -0.03 to -0.01), reaching 244.76 per 100,000 in 2021 (95% UI: 168.02 to 333.99).In 2021, the ASDR in East Asia was 295.90 per 100,000 (95% UI: 207.28 to 393.75), while in the high-income Asia-Pacific region, it was 249.50 per 100,000 (95% UI: 168.01 to 347.54). Age-Stratified Analysis of Depression, Anxiety Disorders, Bipolar Disorder, and Schizophrenia in Women of Reproductive Age Globally The incidence and disease burden of mental disorders in women of reproductive age show significant variation across different age groups worldwide (Figures 1 and 2).In 2021, the incidence of depression was highest among women aged 25–29 years, followed by those aged 30–34 years.Over time, incidence rates increased across all age groups, with the most significant rise observed in the 40–44-year age group.The DALY rate for depression gradually increased with age, peaking among women aged 45–49 years, indicating that the disease burden was heavier in older reproductive-age women (e.g., 40–49 years). The incidence of anxiety disorders peaked in the 25–29-year age group, followed by the 20–24-year group.The DALY rate was highest in the 30–34-year group, and from 1990 to 2021, the DALY rates increased significantly across all age groups.However, the growth rates of incidence and DALY rates were slowest in the 45–49-year age group, indicating that the increase in disease burden in this age group was significantly lower than in others, though the absolute burden remained high. The incidence of bipolar disorder was highest in the 15–19-year age group, while the peak DALY rate was observed in the 25–29-year group (2021: 157.66 per 100,000, 95% UI: 98.33–236.92).Over time, the incidence rate increased most significantly in the 40–44-year group, while the DALY rate in the 45–49-year group declined.Overall, the distribution of bipolar disorder across age groups was relatively uniform, without a clear age-related clustering pattern. Both the incidence and DALY rates of schizophrenia decreased with age.In 2021, the incidence rate was highest in the 20–24-year group, while the peak DALY rate occurred in the 35–39-year group.Over time, the DALY rate increased most significantly in the 30–34-year group, while the incidence and DALY rates in the 45–49-year group remained nearly unchanged, showing close to zero growth. SDI Subgroup Analysis of Depression, Anxiety Disorders, Bipolar Disorder, and Schizophrenia in Women of Reproductive Age Globally The evolution of the disease burden of major mental disorders exhibits significant heterogeneity (Figure 3).The age-standardized disease burden of depression has shown a continuous increase, with the most pronounced growth observed in high-SDI regions, where the final burden level is also the highest.Regions with different SDI levels exhibit opposing trends: the disease burden in high-SDI regions is rising at an accelerating pace, whereas in low-SDI regions, it is gradually declining.This trend is further validated by incidence rates, which remain consistently higher in high-SDI regions than in other areas. The disease burden of anxiety disorders has increased globally over time, displaying a distinct gradient effect. High-SDI regions not only have the highest final burden levels among all SDI categories but also exhibit a much faster growth rate than low-SDI regions.Incidence rate analysis further confirms this socioeconomic gradient, indicating that the risk of developing anxiety disorders in high-SDI regions is at least 1.4 times higher than in low-SDI regions. The overall disease burden of bipolar disorder has remained relatively stable; however, SDI-stratified analysis reveals notable differences.While the final disease burden is highest in high-SDI regions, the most significant growth trend is observed in middle-SDI regions.Incidence rate data indicate that the risk of developing bipolar disorder is approximately 20% higher in resource-rich regions than in low-resource areas, suggesting potential differences in diagnostic capacity. Schizophrenia is the only mental disorder in which the overall burden has remained stable, yet its regional dynamics warrant attention.The disease burden curve in high-SDI regions remains the most stable, whereas a statistically significant upward trend is observed in upper-middle-SDI regions.Furthermore, there is substantial heterogeneity in the rate of change in incidence across SDI levels, with the growth trajectory being the flattest in low-SDI regions. Subgroup analysis of depression, anxiety disorders, bipolar disorder, and schizophrenia among women of reproductive age across 21 global region From 1990 to 2021, the disease burden of schizophrenia, bipolar disorder, anxiety disorders, and depression in women of reproductive age exhibited varying trends across the 21 GBD regions (Figure 4). In 2021, the age-standardized death rate (ASDR) for depression was highest in high-income North America (1,929.21 per 100,000) and Australasia (1,563.09 per 100,000), at 1.8 and 1.5 times the global average, respectively. The disease burden in Central (1,695.20 per 100,000) and Eastern (1,273.15 per 100,000) sub-Saharan Africa increased significantly, possibly due to population growth and limited healthcare resources.In contrast, the ASDR in East Asia declined significantly, possibly due to strengthened mental health interventions. The ASDR for anxiety disorders showed the greatest increase in Tropical Latin America (1,874.23 per 100,000) and Andean Latin America (1,449.82 per 100,000), rising by 69.6% and 40.9% from 1990, respectively.Meanwhile, the ASDR continued to rise in Western sub-Saharan Africa (529.25 per 100,000) and Southeast Asia (810.68 per 100,000), while the growth rate slowed in the high-income Asia-Pacific region (649.35 per 100,000). The ASDR for bipolar disorder remained high in Tropical Latin America (370.63 per 100,000) and Australasia (372.74 per 100,000), at 2.6 times the global average in 2021.Notably, Central (rising from 148.37 to 150.49 per 100,000) and Eastern (rising from 169.77 to 170.81 per 100,000) sub-Saharan Africa showed a slow upward trend. The ASDR for schizophrenia was highest in East Asia (295.90 per 100,000) and Australasia (293.96 per 100,000), both approximately 1.2 times the global average.The ASDR increased in Western (248.20 per 100,000) and Southern (210.80 per 100,000) sub-Saharan Africa, while Eastern Europe (193.92 per 100,000) and the Caribbean (175.90 per 100,000) showed a significant decline. Subgroup analysis of depression, anxiety disorders, bipolar disorder, and schizophrenia among women of reproductive age across 204 countries worldwide Figure 5 illustrates the disease burden (measured in DALYs) of depressive disorders, anxiety disorders, bipolar disorder, and schizophrenia among women of reproductive age across 204 countries in 2021.The DALYs associated with depressive disorders among women of reproductive age vary significantly across the globe. The DALYs values in the Caribbean and Central America were relatively low, ranging from 784.16 to 923.24, whereas those in West Africa were notably higher, reaching between 1,274.65 and 1,877.98.This variation suggests that multiple factors, such as socioeconomic conditions, healthcare accessibility, and cultural influences, contribute to the burden of depressive disorders.In 2021, the global DALYs rate for depressive disorders showed an increasing trend, with the sharpest rise in low-SDI countries.For instance, Lebanon saw a 55.4% increase in the DALYs rate for depressive disorders, while in some South American countries, DALYs rates were over five times higher than in certain African nations. The DALYs values for anxiety disorders ranged from 608.78 to 766.48 in the Caribbean and Central America, while they were notably higher in West Africa, reaching between 1,058.64 and 1,274.65.This variation reflects the diverse impact of anxiety disorders across regions, potentially influenced by social stress and lifestyle factors. In low-SDI countries, the DALYs rate for anxiety disorders rose significantly; for instance, Bolivia saw a 47.2% increase.Anxiety disorders were particularly prevalent in conflict-affected regions. In 2021, the DALYs rates for anxiety disorders in Yemen, South Sudan, and Palestine far exceeded the global average, highlighting the lasting impact of war and displacement on mental health. In the Caribbean region, DALYs values for bipolar disorder and schizophrenia remained relatively low.Compared to depressive and anxiety disorders, bipolar disorder showed less global variation, yet distinct regional differences persisted. For example, in high-income countries like North America and Australia, the disease burden slightly declined, whereas in parts of Eastern Europe and Central Asia, DALYs rates remained high. The DALYs rate for schizophrenia changed minimally but remained consistently high in Eastern European and Central Asian countries. Figure 6 illustrates the incidence distribution of the four mental disorders. The incidence of depressive disorders was relatively low in the Caribbean and Central America (4,556.94 to 5,874.04) but significantly higher in West Africa (10,655.35 to 20,221.09), suggesting that socioeconomic stress, healthcare accessibility, and living conditions may play a substantial role in its prevalence.The incidence of anxiety disorders ranged from 714.2 to 887.56 in the Caribbean and Central America, increasing to 1,066.15 to 1,857.66 in West Africa, highlighting the potential influence of sociocultural background and lifestyle pace on the development of anxiety disorders.The incidence of bipolar disorder was lower in the Caribbean and Central America (30.71 to 45.56) but relatively higher in the Persian Gulf region (29.00 to 36.51), possibly due to genetic factors and differences in diagnostic capabilities.The incidence of schizophrenia was lower in the Caribbean and Central America (21.72 to 22.98) but higher in West Africa (27.63 to 36.51), suggesting that healthcare infrastructure, social support systems, and preventive measures key factors influencing regional differences in schizophrenia incidence. SDI Correlation Analysis of Depression, Anxiety Disorders, Bipolar Disorder, and Schizophrenia Among Women of Reproductive Age Worldwide Analysis of the GBD database reveals distinct associations between SDI and the disease burden and incidence rates of four common mental disorders in women of reproductive age (Figure 7). Both the DALYs of anxiety disorders (Figure 7A) and their incidence rate (Figure 7E) show a gradual increase with rising SDI, with correlation coefficients of 0.50 and 0.42, respectively (both P < 0.001). This suggests that in high-SDI regions, despite greater economic and social development, high-pressure lifestyles and environmental factors may contribute to a higher burden of anxiety disorders. The pattern of bipolar disorder is more complex, as both its DALYs (Figure 7B) and incidence rate (Figure 7F) follow a "W"-shaped relationship, as shown in the figure.When the SDI ranges from 0.4 to 0.6, the disease burden rises significantly, followed by another increase when SDI exceeds 0.7. This suggests that bipolar disorder risk fluctuates in middle-to-low and high SDI ranges, potentially reflecting differences in diagnostic and treatment strategies across economic levels. The DALYs of depression (Figure 7C) show a weak negative correlation with SDI (ρ = -0.08, P = 0.010), while its incidence rate (Figure 7G) has a positive correlation (ρ = 0.44, P < 0.001). This discrepancy suggests that in high-SDI regions, despite a higher incidence of depression, the overall disease burden may be reduced due to more advanced diagnosis, intervention, and treatment strategies. In contrast, in low-SDI regions, limited resources and inadequate early interventions may explain the smaller gap in overall disease burden. However, the reversed trend in incidence rate emphasizes the need for increased attention to low-income female populations. The DALYs (Figure 7D) and incidence rate (Figure 7H) of schizophrenia follow a "U"-shaped trend: the disease burden is lowest when SDI is around 0.6 but increases significantly at both lower and higher SDI levels. This pattern may result from structural factors such as social resource allocation, healthcare accessibility, and treatment adherence in schizophrenia. Overall, the data highlight the "dual acceleration" of global mental health inequality—high disease burden in low-income populations and imbalanced health resources in high-SDI regions, limiting their ability to reduce the burden of certain mental disorders. This trend is most evident in anxiety disorders and schizophrenia, emphasizing the need to strengthen mental health systems in low-SDI regions, improve early interventions, and optimize resource allocation. Analysis of Health Inequities in Depression, Anxiety Disorders, Bipolar Disorder, and Schizophrenia Among Women of Reproductive Age Worldwide Health inequalities in global mental health are becoming more pronounced due to uneven socioeconomic development. This study analyzes DALYs and incidence data to examine four major mental disorders: schizophrenia, bipolar disorder, depression, and anxiety. The Concentration Index (CI) and Slope Index of Inequality (SII) are used to quantify relative and absolute health inequalities (Online Supplementary Figures 1 and 2). Overall, SII indices for all four disorders have risen, while CI indices have declined, reflecting growing disparities in disease burden across socioeconomic strata. Health inequality in anxiety disorders has worsened significantly, with the SII for incidence and DALYs increasing from 278.61 and 196.96 to 432.21 and 330.90, respectively, indicating a rising disease burden among low-income populations. The burden of schizophrenia has shifted toward lower socioeconomic groups, with the DALYs SII rebounding from -842.74 to 465.39. The incidence SII of depression rose from -138.47 to 39.84, while the DALYs gap slightly narrowed. Inequality in bipolar disorder remained stable; however, the disease burden persisted among low-income groups, with the DALYs SII steadily increasing. The CI indices for all four disorders have uniformly declined, indicating a growing distortion in the distribution of disease burden across the socioeconomic spectrum over time. This trend signals a widening global mental health inequality gap, particularly in low-SDI regions, where the burden is escalating at an alarming rate. Urgent action is needed from the international community, national governments, and health institutions to strengthen mental health service frameworks and optimize resource allocation in low-SDI regions. TThese efforts are essential to supporting vulnerable populations with mental disorders and ensuring equitable, accessible mental healthcare. Projection Analysis of Depression, Anxiety Disorders, Bipolar Disorder, and Schizophrenia Among Women of Reproductive Age Worldwide Until 2035 Projections based on the GBD database (Online Supplementary Figures 3) suggest that the disease burden and incidence rates of anxiety disorders and depression among women of reproductive age will significantly increase over the next decade, with this trend accelerating after 2030. This indicates that anxiety disorders and depression may present a greater public health challenge in the future. In contrast, while bipolar disorder and schizophrenia show an upward trend, their growth rates remain moderate. Specifically, both the total DALYs and age-standardized rates for anxiety disorders and depression show a continuous upward trend. The DALYs for anxiety disorders have steadily increased from 1990 to 2020 and are projected to surge dramatically by 2035, with a similar upward trend in age-standardized rates. Similarly, the total DALYs and age-standardized rates for depression have steadily increased, with a more pronounced rise expected in the coming years. In comparison, while the total DALYs and age-standardized rates for bipolar disorder and schizophrenia have increased, their growth has been gradual. DALYs for bipolar disorder have followed a moderate upward trend from 1990 to 2020 and are expected to continue this trajectory through 2035. Similarly, the DALYs and age-standardized rates for schizophrenia exhibit a similar pattern of slow growth. Discussion Main findings This study, based on GBD 2021 data, systematically analyzed the evolution of the disease burden of depression, anxiety disorders, bipolar disorder, and schizophrenia among women of reproductive age worldwide from 1990 to 2021. Key findings include:(1) Globally, the burden of depression and anxiety disorders among women of reproductive age has continued to increase, whereas the prevalence of bipolar disorder and schizophrenia has remained relatively stable. The total number of cases of depression and anxiety disorders has risen significantly, while the incidence rates of schizophrenia and bipolar disorder have shown minimal changes. (2) Age-specific analyses indicate that the burden of depression and anxiety disorders is highest among women aged 25–34, whereas bipolar disorder peaks in the 15–19 age group, and schizophrenia is most prevalent among women aged 20–24. The disability-adjusted life years (DALYs) associated with depression and anxiety disorders have increased most rapidly among women over 40, suggesting that the health burden of mental disorders is particularly severe during midlife in women of reproductive age. (3) Regionally, high-income countries exhibit the highest burden of depression and anxiety disorders, while low-income countries have seen a more rapid increase in the burden of schizophrenia and bipolar disorder. The burden of depression and anxiety has decreased in East Asia and South Asia, while anxiety disorders have increased most significantly in tropical Latin America and Central America. (4) The relationship between SDI (socio-demographic index) levels and the burden of mental disorders is complex. In high-SDI countries, the burden of depression and anxiety disorders has significantly increased, while the burden of schizophrenia follows a "U-shaped" pattern, with the lowest burden in regions with moderate SDI and higher burdens in both low-SDI and high-SDI regions.(5) Countries affected by social unrest and conflict, such as Yemen, South Sudan, and Palestine, have a much higher burden of anxiety disorders compared to the global average. In some countries, such as Bolivia and Lebanon, the burden of depression and anxiety disorders has increased significantly over the past 30 years, highlighting the critical role of socio-economic factors in the prevalence of mental disorders. Reasons for Age-related Differences The age-related differences in mental disorders are primarily influenced by physiological changes, social role transitions, and psychological stress [ 25 ] .The burden of bipolar disorder is highest among females aged 15–19, related to an immature emotional regulation system, unstable neurotransmitter functions, and social conflicts and academic pressures typical of adolescence and the rebellious phase [ 26 ] .Schizophrenia is most common among women aged 20–24, the typical onset age for the disorder. Genetic susceptibility, chronic stress during adolescence, and changes in the university or workplace environment may be key contributing factors [ 27 ] . The burden of depression and anxiety disorders is highest among women aged 25–34, a stage during which women typically face career pressures, increased family responsibilities, and the physiological and psychological changes associated with childbirth and child-rearing [ 28 ] . Additionally, workplace gender discrimination and societal expectations in certain regions may further exacerbate the psychological burden on women [ 29 ] .The burden of depression and anxiety disorders significantly increases among women over 40, which may be associated with the decline in estrogen levels, emotional instability due to menopausal hormonal fluctuations [ 30 ] , reduced social support during the empty nest phase, and the accumulation of long-term psychological stress. Reasons for Differences Across Countries and Regions The differences in the burden of mental disorders across countries are primarily influenced by the level of economic development, healthcare resource allocation, social culture, and public health policies [ 31 ] .High-income countries (e.g., North America, Western Europe) have the highest burden of depression and anxiety disorders, which may be due to the higher rates of mental health disorder recognition and healthcare access in these regions [ 32 ] . Additionally, intense social competition, increased living costs, and high work-related stress have contributed to the rising incidence of depression and anxiety.Furthermore, the acceleration of urbanization, along with the increasing sense of alienation and loneliness in social relationships, may further exacerbate the incidence of anxiety and depression.The burden of schizophrenia and bipolar disorder has grown more rapidly in low-income countries, which may be attributed to a lack of healthcare resources that results in delayed diagnosis and treatment [ 33 ] , thereby worsening the condition.Additionally, the stigma surrounding mental disorders is more pronounced, leading to long-term disability in patients who often lack treatment, thereby increasing the disease burden [ 34 ] .The increasing burden of schizophrenia in sub-Saharan Africa and certain South Asian countries may also be associated with factors such as malnutrition, perinatal infections, and early childhood trauma.In socially unstable regions, such as Yemen, South Sudan, and Palestine, the burden of anxiety disorders is much higher than the global average. These countries have been in a prolonged state of war and social unrest, with large-scale population displacement, economic depression, and the collapse of social support systems. A large portion of the population has experienced traumatic events and post-traumatic stress disorder (PTSD), contributing to the high prevalence of anxiety and depression disorders [ 35 ] . Differences in the Burden Across Different Types of Mental Disorders The burden differences across various types of mental disorders are influenced by a combination of biological, environmental, and social factors [ 36 ] .The burden of depression and anxiety disorders has increased rapidly, which may be related to global economic instability, intensified social competition, information overload (e.g., the widespread use of social media), and changes in lifestyle (e.g., sedentary behavior and lack of physical activity).Additionally, the physiological and psychological challenges women face during periods of social role transitions (e.g., marriage, childbirth, menopause) may further exacerbate symptoms of anxiety and depression.In contrast, the burden of schizophrenia and bipolar disorder remains relatively stable, primarily influenced by genetic factors, with less impact from socio-economic changes on their incidence.However, in low- and middle-income countries, the limited availability of healthcare resources and insufficient social support systems may result in longer disease courses for patients, leading to higher DALYs. Innovations and Highlights of the Study The main innovations of this study are: (1) For the first time, a comprehensive analysis of the global disease burden of four major mental disorders among women of reproductive age (15–49 years) is conducted based on the GBD 2021 data, with long-term trend analysis incorporating age, region, and SDI stratification.(2) The use of the Slope Index of Inequality (SII) reveals that the burden of anxiety disorders is accelerating in lower-income groups (with a 55% increase in the slope from 1990 to 2021), providing a target for mental health policies aimed at "precise poverty alleviation."(3) The study identifies key changing trends in the burden of mental disorders among women across different age groups, emphasizing the mental health risks faced by women of reproductive age during career development, childbirth, and social role transitions.(4) A disease burden model for 2035 is developed, warning that the burden of anxiety and depression will continue to rise. The study calls for proactive planning of digital interventions (such as AI-assisted diagnosis) and integrated perinatal mental health services. Limitations of the Study Despite the extensive data coverage and long time span of this study, certain limitations remain: (1) The study does not analyze specific subtypes of depression, anxiety disorders, bipolar disorder, and schizophrenia, such as major depressive disorder and persistent depressive disorder. This omission may impact the accuracy of the burden assessment for different disease subtypes. (2) The GBD estimates may underestimate the actual burden in conflict zones (e.g., Yemen) or culturally restrictive regions (e.g., conservative religious communities) due to model dependencies and data gaps. This is particularly true for diseases with high diagnostic heterogeneity, such as bipolar disorder. (3) The study does not consider gender roles (e.g., caregiving burdens) or the impact of religious beliefs on treatment adherence. This omission may result in an underestimation of the influence of socio-cultural factors on disease trajectories. Future Directions of the Study The mental health crisis among women of reproductive age is a major challenge in global public health in the 21st century. Based on the study's findings, future actions should focus on three areas: Policy Level, Research Directions, and Social Aspects. In high-SDI regions, it is crucial to promote workplace mental health legislation (e.g., mandatory mental health leave) and integrate mental health services into maternal healthcare systems. In low-SDI regions, the focus should be on expanding service coverage through "mobile clinics" and training community health workers, with a priority on post-trauma interventions in conflict areas. Global collaboration is essential to establish a cross-national mental health monitoring network and implement cross-lifecycle interventions during key windows, such as 25–34 years and 45–49 years. Research Directions: Employ multi-omics technologies to analyze the "social adversity-epigenetics-mental illness" pathway and explore the molecular mechanisms behind the "slope reversal" of depression in low-income groups. Evaluate cases such as China's "Internet + Mental Health" model and Nordic welfare policies, extracting intervention strategies adaptable to different cultural contexts. Social Aspects: The stigma surrounding mental illness should be dismantled, and mental health education should be integrated into basic education curricula, with particular attention to healthcare barriers faced by male anxiety disorder patients. Through interdisciplinary collaboration and data-driven precision strategies, the global community can build a more resilient mental health support system for women of reproductive age, particularly under the dual pressures of aging and urbanization. Declarations Ethics approval and consent to participate This study is a secondary analysis based on publicly available data from the Global Burden of Disease (GBD) 2021 database, provided by the Institute for Health Metrics and Evaluation (IHME). All data are anonymized and aggregated, with no individual-level or identifiable information involved. Therefore, ethical approval and informed consent were not required. Consent for publication Not applicable. Availability of data and materials The datasets generated and analyzed during the current study are publicly available in the Global Burden of Disease (GBD) repository, which can be accessed at:https://vizhub.healthdata.org/gbd-results/. Data sharing statement The data used for the analyses is available by email request to the corresponding author. Competing interests The authors declare that the research was conducted in the absence of anycommercial or financial relationships that could be construed as a potential conflict of interest. Funding This study was supported by the following funding sources: Natural Science Foundation of Henan Province(242300421307); Henan Collaborative Innovation Center of Prevention and Treatment of Mental Disorders(XTkf11); Henan Provincial Key Research and Development Special Project2025（251111520600）; National Natural Science Foundation of China (82374273); Key issues of education and teaching reform in Henan province（2024SJGLX0141）. Authors’ contributions This study was led by Junqiang Zhao, with Junyao Li responsible for the overall design, data analysis, and manuscript writing. Bo Song, Min Cai, and Wanqi Sun provided data analysis and methodological support. Luping Wang were responsible for language editing and formatting. Shichang Yang and Xiaohong Kang provided expert opinions, assisting in the interpretation of the clinical significance of the mental disorders burden, and participated in the review of the manuscript structure. All authors made significant contributions to the successful completion of the study. Acknowledgements We sincerely acknowledge the Global Burden of Disease (GBD) Study for providing open-access data that contributed to this research. We are deeply grateful to Prof. Junqiang Zhao, Prof. Shichang Yang, and Prof. Xiaohong Kang for their invaluable guidance and insightful suggestions throughout the study. Their expertise and continuous support have played a crucial role in the development of this research. Additionally, this study was supported by the Natural Science Foundation of Henan Province (Grant No. 242300421307), the Henan Collaborative Innovation Center of Prevention and Treatment of Mental Disorders (Grant No. XTkf11), the Henan Provincial Key Research and Development Special Project 2025 (Grant No. 251111520600), the National Natural Science Foundation of China (Grant No. 82374273), and the Key Issues of Education and Teaching Reform in Henan Province (Grant No. 2024SJGLX0141). We sincerely appreciate the financial support provided by these institutions. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Any product evaluated in this article or claim made by its manufacturer is not guaranteed or endorsed by the publisher. 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A Multi-Level Analysis of Biological, Social, and Psychological Determinants of Substance Use Disorder and Co-Occurring Mental Health Outcomes [J]. Psychoactives. 2024;3(2):194–214. Additional Declarations No competing interests reported. Supplementary Files OnlineSupplementaryTable1.png OnlineSupplementaryTable2.png OnlineSupplementaryFigure1.tif OnlineSupplementaryFigure2.tif OnlineSupplementaryFigure3.tif Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 04 Jul, 2025 Reviewers agreed at journal 04 Jul, 2025 Reviewers invited by journal 04 Jul, 2025 Editor invited by journal 22 May, 2025 Editor assigned by journal 19 May, 2025 Submission checks completed at journal 19 May, 2025 First submitted to journal 16 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6678574","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":480826396,"identity":"c7b19dce-a8fa-4333-af48-5e117dd47437","order_by":0,"name":"Junyao Li","email":"","orcid":"","institution":"Xinxiang Medical University","correspondingAuthor":false,"prefix":"","firstName":"Junyao","middleName":"","lastName":"Li","suffix":""},{"id":480826397,"identity":"b5bf69ba-4e1c-45d5-9e30-095bc490220e","order_by":1,"name":"Bo Song","email":"","orcid":"","institution":"Xinxiang Medical 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06:26:19","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":332994,"visible":true,"origin":"","legend":"\u003cp\u003eAge-Specific DALYs Rate Components of Bipolar Disorder (A), Anxiety Disorders (B), Schizophrenia (C), and Depression (D) Among Women of Reproductive Age Globally, 1990–2019.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6678574/v1/6696c68f89fac5179c3035e6.png"},{"id":86389369,"identity":"ac0a3e6b-07f7-4015-829e-a5b2e16f0de6","added_by":"auto","created_at":"2025-07-10 06:34:19","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":327784,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of age-standardized trends in incidence (A) and DALY rates (B) of depression, schizophrenia, anxiety disorders, and bipolar disorder among women of \u0026nbsp;reproductive age across different SDI levels globally in 1990 and 2021\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6678574/v1/839524363d6f6a082a728ae2.png"},{"id":86389074,"identity":"8307927c-a316-496e-b51b-15dec800597c","added_by":"auto","created_at":"2025-07-10 06:26:19","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":187864,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of age-standardized trends in incidence (A) and DALY rates (B) of depression, schizophrenia, anxiety disorders, and bipolar disorder among women of reproductive age across different global regions in 1990 and 2021\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-6678574/v1/02f074e4a1c3ae6c9691eb55.png"},{"id":86389080,"identity":"a4cff335-71d4-432c-a6a6-58f9141e48ba","added_by":"auto","created_at":"2025-07-10 06:26:19","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":1677901,"visible":true,"origin":"","legend":"\u003cp\u003eGlobal distribution of DALYs for depressive disorders (A), anxiety disorders (B), bipolar disorder (C), and schizophrenia (D) among women of reproductive age across 204 countries in 2021.\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-6678574/v1/e49627206b07a415c9280741.png"},{"id":86389086,"identity":"10817da5-6b6e-4e0a-873e-788883695149","added_by":"auto","created_at":"2025-07-10 06:26:19","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":1659432,"visible":true,"origin":"","legend":"\u003cp\u003eGlobal distribution of incidence for depressive disorders (A), anxiety disorders (B), bipolar \u0026nbsp;disorder (C), and schizophrenia (D) among women of reproductive age across 204 countries in 2021.\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-6678574/v1/03f500adbe1a96e4fdae90bd.png"},{"id":86389099,"identity":"8998dff9-0fe9-4537-9499-b65deb5a47a4","added_by":"auto","created_at":"2025-07-10 06:26:20","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":899256,"visible":true,"origin":"","legend":"\u003cp\u003eThe correlation between SDI and the DALYs (A–D) of anxiety disorders, bipolar disorder, depression, and schizophrenia among women of reproductive age, as well as the \u0026nbsp;correlation between SDI and their incidence rates (E–H).\u003c/p\u003e","description":"","filename":"floatimage7.png","url":"https://assets-eu.researchsquare.com/files/rs-6678574/v1/790010300fee6b0575f2e79e.png"},{"id":86391573,"identity":"ae33272d-4f68-4ba6-998c-138f0e41215e","added_by":"auto","created_at":"2025-07-10 06:58:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":6118976,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6678574/v1/60c7fc96-8f8c-4cda-aa63-2e9e6cd52397.pdf"},{"id":86389076,"identity":"9510b85f-33da-4faf-a570-aa95db8e1db3","added_by":"auto","created_at":"2025-07-10 06:26:19","extension":"png","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":576264,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineSupplementaryTable1.png","url":"https://assets-eu.researchsquare.com/files/rs-6678574/v1/c015cac821cb4d1764cec798.png"},{"id":86389077,"identity":"8b4da2b5-8eb3-478f-b134-ec9aa934c656","added_by":"auto","created_at":"2025-07-10 06:26:19","extension":"png","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":594246,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineSupplementaryTable2.png","url":"https://assets-eu.researchsquare.com/files/rs-6678574/v1/1c6df299f85e961c2ecc0577.png"},{"id":86389071,"identity":"232c4dfa-e31a-4145-8fdb-8f8f4c19fa07","added_by":"auto","created_at":"2025-07-10 06:26:19","extension":"tif","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":863152,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineSupplementaryFigure1.tif","url":"https://assets-eu.researchsquare.com/files/rs-6678574/v1/78b56243e1828f2168ee64dc.tif"},{"id":86389091,"identity":"c317ee04-533b-411b-8460-686bf3452a04","added_by":"auto","created_at":"2025-07-10 06:26:20","extension":"tif","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":898730,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineSupplementaryFigure2.tif","url":"https://assets-eu.researchsquare.com/files/rs-6678574/v1/30e322ecfbdefa27dbc8b179.tif"},{"id":86389075,"identity":"a03600b3-f2ad-4ec9-8816-ec868b776868","added_by":"auto","created_at":"2025-07-10 06:26:19","extension":"tif","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":555815,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineSupplementaryFigure3.tif","url":"https://assets-eu.researchsquare.com/files/rs-6678574/v1/0ae80d126daa7d6c8119bfb7.tif"}],"financialInterests":"No competing interests reported.","formattedTitle":"Global Burden of Mental Disorders in Women of Reproductive Age from 1990 to 2021: A Comprehensive Analysis and Trend Prediction of Depression, Anxiety, Bipolar Disorder, and Schizophrenia","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAccording to the 2019 Global Burden of Disease (GBD 2019) study published in The Lancet Psychiatry, mental disorders rank among the top ten contributors to the global disease burden, with disability rates among the top three. They account for 4.9% of global DALYs, and their burden has shown a significant upward trend since 1990\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e.Mental disorders exhibit a distinct early-onset and chronic progression pattern, affecting approximately 970\u0026nbsp;million people worldwide. Among them, more than 380\u0026nbsp;million suffer from depression, and 301\u0026nbsp;million experience anxiety disorders \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. Additionally, 50% of patients experience their first onset before the age of 24 \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e.Cognitive impairment and emotional dysregulation caused by mental disorders not only reduce occupational functioning and weaken social relationships but also impose a substantial economic burden\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eFrom an economic perspective, the cost structure of mental disorders is characterized by \"low direct medical expenditures and high hidden social losses.\"For example, the annual direct medical costs for patients with depression range from \u003cspan\u003e$\u003c/span\u003e1,200 to \u003cspan\u003e$\u003c/span\u003e4,500, while for those with severe mental disorders requiring long-term hospitalization, the annual costs can reach \u003cspan\u003e$\u003c/span\u003e10,000 to \u003cspan\u003e$\u003c/span\u003e60,000 \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e.However, due to a global treatment gap of 50%, direct medical expenditures account for only 37% of the total burden \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e.More critically, anxiety disorder patients experience a 28% reduction in annual income due to decreased work efficiency, while schizophrenia patients face a lifetime income loss of up to \u003cspan\u003e$\u003c/span\u003e1.23\u0026nbsp;million \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e.Additionally, depression patients have an increased risk of cardiovascular comorbidities \u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e, leading to higher medical costs, which together create a dual economic burden of productivity loss and comorbidity-related expenses.\u003c/p\u003e\u003cp\u003eNotably, women of reproductive age are at high risk for mental disorders due to a combination of biological and social vulnerabilities.For example, 40% of Chinese women experience depressive states during pregnancy \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e, and globally, the years lived with disability (YLDs) due to depression are significantly higher in women of reproductive age than in men \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e.Moreover, endogenous hormone levels (such as estradiol) not only influence emotional stability and mental health in women of reproductive age but may also increase the risk of cognitive decline and neurodegenerative diseases after menopause \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e.Studies indicate that hormonal fluctuations increase the risk of perinatal depression \u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e, and public health emergencies may further exacerbate this risk \u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e.Since the outbreak of COVID-19 in late 2019, global prevalence rates of anxiety and depression have risen significantly. The World Health Organization (WHO) reported that the pandemic led to a 25% increase in global anxiety and depression prevalence \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e.Young people and women have been the most severely affected, and pregnant women, as a particularly vulnerable group, are especially prone to anxiety and depression during the pandemic.Depression and anxiety have a high comorbidity rate among women of reproductive age, with potential mutual influence and conversion between the two disorders \u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e.Social role conflicts may further contribute to the higher prevalence of anxiety disorders in women compared to men.Meanwhile, the global 50% treatment gap and the stigma surrounding mental illness further exacerbate the challenges faced by women of reproductive age \u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e.Studies show that 75% of women with mental disorders do not receive standardized treatment \u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e, which not only increases the risk of cognitive decline in menopause but also reinforces the negative interaction chain of \"biological susceptibility\u0026ndash;social stress\u0026ndash;economic deprivation.\"Therefore, a systematic analysis of the evolution of the mental disorder burden among women of reproductive age from 1990 to 2019 is crucial for breaking this interaction chain.\u003c/p\u003e\u003cp\u003eUnlike traditional epidemiological studies, the GBD database employs a globally standardized Bayesian mixed-effects model, integrating multi-source heterogeneous data while systematically correcting for diagnostic inconsistencies and underreporting biases. This enables spatiotemporal comparability in disease incidence estimates \u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e.Based on GBD 2021 data, this study systematically analyzes the burden of mental disorders among women of reproductive age worldwide and quantifies the disparities in disease burden across different regions and populations. The findings provide scientific evidence for precision prevention strategies and adaptive health policies.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eData source\u003c/h2\u003e\u003cp\u003eThe 2021 GBD estimated the incidence and DALYs of mental disorders in 204 countries and regions from 1990 to 2021.This study focuses on the incidence and disability trends of depression, anxiety disorders, bipolar disorder, and schizophrenia in women of reproductive age worldwide from 1990 to 2021.Additionally, we analyzed age-group differences within this population, categorizing them into seven subgroups: 15\u0026ndash;20, 21\u0026ndash;25, 26\u0026ndash;30, 31\u0026ndash;35, 36\u0026ndash;40, 41\u0026ndash;45, and 46\u0026ndash;49 years.\u003c/p\u003e\u003cp\u003eData on the incidence and DALYs of depression, anxiety disorders, bipolar disorder, and schizophrenia in specific populations were obtained from the publicly available Institute for Health Metrics and Evaluation (IHME) online tool (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://vizhub.healthdata.org/gbd-results/\u003c/span\u003e\u003cspan address=\"https://vizhub.healthdata.org/gbd-results/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e)\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e.Data coding follows the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), or the International Classification of Diseases, Eleventh Revision (ICD-11), and is based on confirmed cases of depression, anxiety disorders, bipolar disorder, and schizophrenia.The ASIR and ASDR of these mental health conditions were analyzed by region, country, age, and year. Population data for women of reproductive age were obtained from the World Population Prospects 2019 (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.un.org/zh/desa/world-population-prospects-2019\u003c/span\u003e\u003cspan address=\"https://www.un.org/zh/desa/world-population-prospects-2019\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e), a report by the United Nations Department of Economic and Social Affairs, Population Division, providing official estimates and projections \u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eA descriptive analysis of cases per 100,000 people worldwide, stratified by age group, was conducted to assess the burden of depression, anxiety disorders, bipolar disorder, and schizophrenia among women of reproductive age. The results were reported with a 95% UI, derived from 1,000 posterior distribution samples per variable, using the 2.5th and 97.5th percentiles of the uncertainty distribution. The EAPC was used to assess disease burden trends from 1990 to 2021 and estimate the disease burden in 2021\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. The ASDR for each study year was collected, with the calendar year used as a regression factor. A regression model was fitted to the natural logarithm of these rates, yielding the equation: ln(rate) = α\u0026thinsp;+\u0026thinsp;β * calendar year, where β represents the EAPC.The EAPC and its 95% confidence interval (CI) were calculated using the equation: EAPC\u0026thinsp;=\u0026thinsp;100 * (e^β\u0026thinsp;\u0026minus;\u0026thinsp;1).Additionally, ASIR and ASDR data for depression, anxiety disorders, bipolar disorder, and schizophrenia were analyzed using the same methods. All statistical analyses were conducted in R software (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.r-project.org/\u003c/span\u003e\u003cspan address=\"https://www.r-project.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) with a significance level of 0.05.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003col\u003e\n\u003cli\u003eIncidence of Depression, Anxiety, Bipolar Disorder, and Schizophrenia Among Women of Reproductive Age\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eTable 1 (Online Supplementary Table 1) summarizes key findings from the 2021 GBD study on the incidence and ASIR of depression, anxiety, bipolar disorder, and schizophrenia from 1990 to 2021 across the world, 21 regions, and five SDI groups.Globally, the number of depression cases among women of reproductive age increased from 77.72 million (95% UI: 58,860,491 to 102,539,344) in 1990 to 133 million (95% UI: 99,032,450 to 177,876,463) in 2021. However, the ASIR increased slightly from 5,898.5 per 100,000 population (95% UI: 4,486.52 to 7,740.66) to 6,808.01 per 100,000 (95% UI: 5,049.99 to 9,106.66), with an estimated annual percentage change (EAPC) of -0.18 (95% CI: -0.39 to 0.04).Significant regional variations were observed. In 2021, Australasia (10,269.64 per 100,000, 95% UI: 7,057.12 to 14,369.31), Central Sub-Saharan Africa (11,270.02 per 100,000, 95% UI: 7,523.17 to 16,274.56), and high-income North America (12,689.95 per 100,000, 95% UI: 9,828.58 to 16,139.08) reported the highest ASIRs.In contrast, the lowest ASIRs were recorded in East Asia (2,956.12 per 100,000, 95% UI: 2,227.57 to 3,840.52) and Western Sub-Saharan Africa (6,114.54 per 100,000, 95% UI: 4,369.47 to 8,446.05).Central America exhibited the fastest-growing ASIR (EAPC = 1.02, 95% CI: 0.80 to 1.24). In contrast, East Asia (EAPC = -1.40, 95% CI: -1.65 to -1.16), South Asia (EAPC = -0.99, 95% CI: -1.31 to -0.66), and low-SDI regions (EAPC = -0.36, 95% CI: -0.53 to -0.19) experienced significant declines.\u003c/p\u003e\n\u003cp\u003eGlobally, anxiety cases among women of reproductive age rose from 107 million (95% UI: 70,583,850 to 149,386,510) in 1990 to 190 million (95% UI: 126,600,290 to 262,953,960) in 2021. The ASIR increased from 797.81 per 100,000 (95% UI: 527.95 to 1,108.31) to 976.14 per 100,000 (95% UI: 650.09 to 1,355.11), with an EAPC of 0.24 (95% CI: 0.08 to 0.39).Tropical Latin America saw the largest increase in ASIR (EAPC = 1.08, 95% CI: 0.76 to 1.40), reaching 1,851.05 per 100,000 (95% UI: 1,223.06 to 2,604.60) in 2021. High-income North America (EAPC = 0.82, 95% CI: 0.47 to 1.16) and Central America (EAPC = 0.74, 95% CI: 0.53 to 0.95) also showed a rapid upward trend. In contrast, significant declines in ASIR occurred in East Asia (EAPC = -0.53, 95% CI: -0.69 to -0.37) and high-income Asia Pacific (EAPC = -0.16, 95% CI: -0.33 to 0.00). In 2021, the highest ASIRs were recorded in Tropical Latin America (1,851.05 per 100,000, 95% UI: 1,223.06 to 2,604.60) and high-income North America (1,576.93 per 100,000, 95% UI: 1,055.10 to 2,175.10).\u003c/p\u003e\n\u003cp\u003eGlobally, the number of bipolar disorder cases among women of reproductive age rose from 575,600 (95% UI: 344,082 to 875,035) in 1990 to 826,400 (95% UI: 484,408 to 1,270,443) in 2021. However, the ASIR showed only a modest increase from 41.64 per 100,000 (95% UI: 24.69 to 63.45) to 43.16 per 100,000 (95% UI: 25.43 to 66.23), with an EAPC of 0.09 (95% CI: 0.07 to 0.11).A slight increase in ASIR was observed in middle-SDI regions (EAPC = 0.26, 95% CI: 0.22 to 0.30) and high-income North America (EAPC = 0.06, 95% CI: 0.04 to 0.08), whereas Eastern Europe (EAPC = -0.01, 95% CI: -0.01 to -0.01) and East Asia (EAPC = -0.02, 95% CI: -0.03 to -0.01) saw slight decline.In 2021, the highest ASIRs were recorded in Tropical Latin America (95.70 per 100,000, 95% UI: 59.41 to 141.64) and Andean Latin America (76.95 per 100,000, 95% UI: 42.16 to 125.71).\u003c/p\u003e\n\u003cp\u003eGlobally, the number of schizophrenia cases among women of reproductive age rose from 378,300 (95% UI: 227,553 to 559,592) in 1990 to 513,300 (95% UI: 302,798 to 767,916) in 2021. However, the ASIR showed a slight decrease from 26.98 per 100,000 (95% UI: 16.19 to 40.01) to 26.71 per 100,000 (95% UI: 15.76 to 39.94), with an EAPC of -0.02 (95% CI: -0.03 to -0.01).A significant increase in ASIR was observed in Eastern Europe (EAPC = 0.19, 95% CI: 0.15 to 0.22) and high-income Asia Pacific (EAPC = 0.22, 95% CI: 0.15 to 0.29), while middle-SDI regions (EAPC = -0.09, 95% CI: -0.10 to -0.08) and Western Europe (EAPC = -0.04, 95% CI: -0.06 to -0.02) showed a downward trend.In 2021, the highest ASIRs were recorded in Eastern Europe (6,990.81 per 100,000, 95% UI: 4,956.63 to 9,586.01) and high-income North America (12,689.95 per 100,000, 95% UI: 9,828.58 to 16,139.08).\u003c/p\u003e\n\u003col start=\"2\"\u003e\n\u003cli\u003eThe DALYs of depression, anxiety disorders, bipolar disorder, and schizophrenia in women of reproductive age\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eTable 2 (Online supplementary table 2) presents the key GBD study results on DALYs and ASDR for depression, anxiety disorders, bipolar disorder, and schizophrenia from 1990 to 2021 across the globe, 21 regions, and 5 SDI groups.\u003c/p\u003e\n\u003cp\u003eBetween 1990 and 2021, the DALYs of depression among women of reproductive age globally increased from 12.445 million (95% UI: 8,084,219 to 18,023,437) to 21.042 million (95% UI: 13,468,194 to 30,593,481), while the ASDR rose from 948.86 per 100,000 (95% UI: 617.06 to 1,369.93) to 1,073.5 per 100,000 (95% UI: 686.73 to 1,562.48), with an EAPC of -0.14 (95% CI: -0.32 to 0.04).Significant regional differences were observed: high-income North America saw the largest increase in ASDR (EAPC = 0.64, 95% CI: 0.36 to 0.92), reaching 1,929.21 per 100,000 in 2021 (95% UI: 1,284.02 to 2,772.95), while East Asia experienced a significant decrease (EAPC = -1.15, 95% CI: -1.34 to -0.95), with an ASDR of 560.51 per 100,000 in 2021 (95% UI: 365.80 to 799.17). Sub-Saharan Africa (Central) had the highest ASDR in 2021 (1,695.20 per 100,000, 95% UI: 994.94 to 2,610.73), but the trend remained stable (EAPC=0.02, 95% CI: -0.07 to 0.12).\u003c/p\u003e\n\u003cp\u003eThe DALYs of anxiety disorders in women of reproductive age globally increased from 9.329 million (95% UI: 5,917,676 to 13,620,685) in 1990 to 16.448 million (95% UI: 10,383,333 to 24,009,992) in 2021. The ASDR rose from 698.30 per 100,000 (95% UI: 442.60 to 1,018.65) to 844.05 per 100,000 (95% UI: 532.79 to 1,232.57), with an EAPC of 0.16 (95% CI: 0.01 to 0.32).Tropical Latin America saw the largest increase in ASDR (EAPC = 1.40, 95% CI: 0.88 to 1.93), reaching 1,874.23 per 100,000 in 2021 (95% UI: 1,199.81 to 2,688.52). In contrast, the ASDR in East Asia declined (EAPC=-0.53, 95% CI: -0.70 to -0.37), decreasing to 616.80 per 100,000 in 2021 (95% UI: 390.72 to 913.98). Additionally, regions with higher ASDRs in 2021 include high-income North America at 1,414.22 per 100,000 (95% UI: 916.57 to 2,054.75), and Western Europe at 1,333.41 per 100,000 (95% UI: 827.15 to 1,967.63).\u003c/p\u003e\n\u003cp\u003eThe DALYs of bipolar disorder in women of reproductive age globally increased from 1.89 million (95% UI: 1,181,247 to 2,850,106) in 1990 to 2.807 million (95% UI: 1,740,129 to 4,226,051) in 2021. The ASDR slightly increased from 142.30 per 100,000 (95% UI: 88.88 to 214.07) to 143.77 per 100,000 (95% UI: 89.11 to 216.63), with an EAPC of 0.03 (95% CI: 0.02 to 0.04).In regions with moderate SDI, the ASDR slightly increased (EAPC=0.26, 95% CI: 0.24 to 0.28), reaching 138.24 per 100,000 in 2021 (95% UI: 85.78 to 208.03). In high-income North America, the ASDR declined (EAPC = -0.04, 95% CI: -0.05 to -0.03), reaching 197.04 per 100,000 in 2021 (95% UI: 128.19 to 283.58).In 2021, Tropical Latin America had the highest ASDR (368.90 per 100,000, 95% UI: 233.33 to 551.85), followed closely by Andean Latin America (281.66 per 100,000, 95% UI: 161.72 to 449.59), but both regions had EAPCs close to zero.\u003c/p\u003e\n\u003cp\u003eThe DALYs of schizophrenia in women of reproductive age globally increased from 3.115 million (95% UI: 2,138,675 to 4,238,277) in 1990 to 4.837 million (95% UI: 3,318,473 to 6,567,286) in 2021. The ASDR slightly decreased from 244.12 per 100,000 (95% UI: 168.33 to 329.91) to 243.46 per 100,000 (95% UI: 166.79 to 331.29), with an EAPC of 0.00 (95% CI: 0.00 to 0.01).The ASDR in Eastern Europe showed a significant increase (EAPC = 0.21, 95% CI: 0.17 to 0.26), reaching 193.92 per 100,000 in 2021 (95% UI: 130.80 to 265.36).In regions with a moderate SDI, the ASDR declined (EAPC = -0.02, 95% CI: -0.03 to -0.01), reaching 244.76 per 100,000 in 2021 (95% UI: 168.02 to 333.99).In 2021, the ASDR in East Asia was 295.90 per 100,000 (95% UI: 207.28 to 393.75), while in the high-income Asia-Pacific region, it was 249.50 per 100,000 (95% UI: 168.01 to 347.54).\u003c/p\u003e\n\u003col start=\"3\"\u003e\n\u003cli\u003eAge-Stratified Analysis of Depression, Anxiety Disorders, Bipolar Disorder, and Schizophrenia in Women of Reproductive Age Globally\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eThe incidence and disease burden of mental disorders in women of reproductive age show significant variation across different age groups worldwide (Figures 1 and 2).In 2021, the incidence of depression was highest among women aged 25\u0026ndash;29 years, followed by those aged 30\u0026ndash;34 years.Over time,\u0026nbsp; incidence rates increased across all age groups, with the most significant rise observed in the 40\u0026ndash;44-year age group.The DALY rate for depression gradually increased with age, peaking among women aged 45\u0026ndash;49 years, indicating that the disease burden was heavier in older reproductive-age women (e.g., 40\u0026ndash;49 years).\u003c/p\u003e\n\u003cp\u003eThe incidence of anxiety disorders peaked in the 25\u0026ndash;29-year age group, followed by the 20\u0026ndash;24-year group.The DALY rate was highest in the 30\u0026ndash;34-year group, and from 1990 to 2021, the DALY rates increased significantly across all age groups.However, the growth rates of incidence and DALY rates were slowest in the 45\u0026ndash;49-year age group, indicating that the increase in disease burden in this age group was significantly lower than in others, though the absolute burden remained high.\u003c/p\u003e\n\u003cp\u003eThe incidence of bipolar disorder was highest in the 15\u0026ndash;19-year age group, while the peak DALY rate was observed in the 25\u0026ndash;29-year group (2021: 157.66 per 100,000, 95% UI: 98.33\u0026ndash;236.92).Over time, the incidence rate increased most significantly in the 40\u0026ndash;44-year group, while the DALY rate in the 45\u0026ndash;49-year group declined.Overall, the distribution of bipolar disorder across age groups was relatively uniform, without a clear age-related clustering pattern.\u003c/p\u003e\n\u003cp\u003eBoth the incidence and DALY rates of schizophrenia decreased with age.In 2021, the incidence rate was highest in the 20\u0026ndash;24-year group, while the peak DALY rate occurred in the 35\u0026ndash;39-year group.Over time, the DALY rate increased most significantly in the 30\u0026ndash;34-year group, while the incidence and DALY rates in the 45\u0026ndash;49-year group remained nearly unchanged, showing close to zero growth.\u003c/p\u003e\n\u003col start=\"4\"\u003e\n\u003cli\u003eSDI Subgroup Analysis of Depression, Anxiety Disorders, Bipolar Disorder, and Schizophrenia in Women of Reproductive Age Globally\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eThe evolution of the disease burden of major mental disorders exhibits significant heterogeneity (Figure 3).The age-standardized disease burden of depression has shown a continuous increase, with the most pronounced growth observed in high-SDI regions, where the final burden level is also the highest.Regions with different SDI levels exhibit opposing trends: the disease burden in high-SDI regions is rising at an accelerating pace, whereas in low-SDI regions, it is gradually declining.This trend is further validated by incidence rates, which remain consistently higher in high-SDI regions than in other areas.\u003c/p\u003e\n\u003cp\u003eThe disease burden of anxiety disorders has increased globally over time, displaying a distinct gradient effect. High-SDI regions not only have the highest final burden levels among all SDI categories but also exhibit a much faster growth rate than low-SDI regions.Incidence rate analysis further confirms this socioeconomic gradient, indicating that the risk of developing anxiety disorders in high-SDI regions is at least 1.4 times higher than in low-SDI regions.\u003c/p\u003e\n\u003cp\u003eThe overall disease burden of bipolar disorder has remained relatively stable; however, SDI-stratified analysis reveals notable differences.While the final disease burden is highest in high-SDI regions, the most significant growth trend is observed in middle-SDI regions.Incidence rate data indicate that the risk of developing bipolar disorder is approximately 20% higher in resource-rich regions than in low-resource areas, suggesting potential differences in diagnostic capacity.\u003c/p\u003e\n\u003cp\u003eSchizophrenia is the only mental disorder in which the overall burden has remained stable, yet its regional dynamics warrant attention.The disease burden curve in high-SDI regions remains the most stable, whereas a statistically significant upward trend is observed in upper-middle-SDI regions.Furthermore, there is substantial heterogeneity in the rate of change in incidence across SDI levels, with the growth trajectory being the flattest in low-SDI regions.\u003c/p\u003e\n\u003col start=\"5\"\u003e\n\u003cli\u003eSubgroup analysis of depression, anxiety disorders, bipolar disorder, and schizophrenia among women of reproductive age across 21 global region\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eFrom 1990 to 2021, the disease burden of schizophrenia, bipolar disorder, anxiety disorders, and depression in women of reproductive age exhibited varying trends across the 21 GBD regions (Figure 4).\u003c/p\u003e\n\u003cp\u003eIn 2021, the age-standardized death rate (ASDR) for depression was highest in high-income North America (1,929.21 per 100,000) and Australasia (1,563.09 per 100,000), at 1.8 and 1.5 times the global average, respectively. The disease burden in Central (1,695.20 per 100,000) and Eastern (1,273.15 per 100,000) sub-Saharan Africa increased significantly, possibly due to population growth and limited healthcare resources.In contrast, the ASDR in East Asia declined significantly, possibly due to strengthened mental health interventions.\u003c/p\u003e\n\u003cp\u003eThe ASDR for anxiety disorders showed the greatest increase in Tropical Latin America (1,874.23 per 100,000) and Andean Latin America (1,449.82 per 100,000), rising by 69.6% and 40.9% from 1990, respectively.Meanwhile, the ASDR continued to rise in Western sub-Saharan Africa (529.25 per 100,000) and Southeast Asia (810.68 per 100,000), while the growth rate slowed in the high-income Asia-Pacific region (649.35 per 100,000).\u003c/p\u003e\n\u003cp\u003eThe ASDR for bipolar disorder remained high in Tropical Latin America (370.63 per 100,000) and Australasia (372.74 per 100,000), at 2.6 times the global average in 2021.Notably, Central (rising from 148.37 to 150.49 per 100,000) and Eastern (rising from 169.77 to 170.81 per 100,000) sub-Saharan Africa showed a slow upward trend.\u003c/p\u003e\n\u003cp\u003eThe ASDR for schizophrenia was highest in East Asia (295.90 per 100,000) and Australasia (293.96 per 100,000), both approximately 1.2 times the global average.The ASDR increased in Western (248.20 per 100,000) and Southern (210.80 per 100,000) sub-Saharan Africa, while Eastern Europe (193.92 per 100,000) and the Caribbean (175.90 per 100,000) showed a significant decline.\u003c/p\u003e\n\u003col start=\"6\"\u003e\n\u003cli\u003eSubgroup analysis of depression, anxiety disorders, bipolar disorder, and schizophrenia among women of reproductive age across 204 countries worldwide\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eFigure 5 illustrates the disease burden (measured in DALYs) of depressive disorders, anxiety disorders, bipolar disorder, and schizophrenia among women of reproductive age across 204 countries in 2021.The DALYs associated with depressive disorders among women of reproductive age vary significantly across the globe. The DALYs values in the Caribbean and Central America were relatively low, ranging from 784.16 to 923.24, whereas those in West Africa were notably higher, reaching between 1,274.65 and 1,877.98.This variation suggests that multiple factors, such as socioeconomic conditions, healthcare accessibility, and cultural influences, contribute to the burden of depressive disorders.In 2021, the global DALYs rate for depressive disorders showed an increasing trend, with the sharpest rise in low-SDI countries.For instance, Lebanon saw a 55.4% increase in the DALYs rate for depressive disorders, while in some South American countries, DALYs rates were over five times higher than in certain African nations. The DALYs values for anxiety disorders ranged from 608.78 to 766.48 in the Caribbean and Central America, while they were notably higher in West Africa, reaching between 1,058.64 and 1,274.65.This variation reflects the diverse impact of anxiety disorders across regions, potentially influenced by social stress and lifestyle factors. In low-SDI countries, the DALYs rate for anxiety disorders rose significantly; for instance, Bolivia saw a 47.2% increase.Anxiety disorders were particularly prevalent in conflict-affected regions. In 2021, the DALYs rates for anxiety disorders in Yemen, South Sudan, and Palestine far exceeded the global average, highlighting the lasting impact of war and displacement on mental health. In the Caribbean region, DALYs values for bipolar disorder and schizophrenia remained relatively low.Compared to depressive and anxiety disorders, bipolar disorder showed less global variation, yet distinct regional differences persisted. For example, in high-income countries like North America and Australia, the disease burden slightly declined, whereas in parts of Eastern Europe and Central Asia, DALYs rates remained high. The DALYs rate for schizophrenia changed minimally but remained consistently high in Eastern European and Central Asian countries.\u003c/p\u003e\n\u003cp\u003eFigure 6 illustrates the incidence distribution of the four mental disorders. The incidence of depressive disorders was relatively low in the Caribbean and Central America (4,556.94 to 5,874.04) but significantly higher in West Africa (10,655.35 to 20,221.09), suggesting that socioeconomic stress, healthcare accessibility, and living conditions may play a substantial role in its prevalence.The incidence of anxiety disorders ranged from 714.2 to 887.56 in the Caribbean and Central America, increasing to 1,066.15 to 1,857.66 in West Africa, highlighting the potential influence of sociocultural background and lifestyle pace on the development of anxiety disorders.The incidence of bipolar disorder was lower in the Caribbean and Central America (30.71 to 45.56) but relatively higher in the Persian Gulf region (29.00 to 36.51), possibly due to genetic factors and differences in diagnostic capabilities.The incidence of schizophrenia was lower in the Caribbean and Central America (21.72 to 22.98) but higher in West Africa (27.63 to 36.51), suggesting that healthcare infrastructure, social support systems, and preventive measures key factors influencing regional differences in schizophrenia incidence.\u003c/p\u003e\n\u003cp\u003eSDI Correlation Analysis of Depression, Anxiety Disorders, Bipolar Disorder, and Schizophrenia Among Women of Reproductive Age Worldwide\u003c/p\u003e\n\u003cp\u003eAnalysis of the GBD database reveals distinct associations between SDI and the disease burden and incidence rates of four common mental disorders in women of reproductive age (Figure 7). Both the DALYs of anxiety disorders (Figure 7A) and their incidence rate (Figure 7E) show a gradual increase with rising SDI, with correlation coefficients of 0.50 and 0.42, respectively (both P \u0026lt; 0.001). This suggests that in high-SDI regions, despite greater economic and social development, high-pressure lifestyles and environmental factors may contribute to a higher burden of anxiety disorders.\u003c/p\u003e\n\u003cp\u003eThe pattern of bipolar disorder is more complex, as both its DALYs (Figure 7B) and incidence rate (Figure 7F) follow a \"W\"-shaped relationship, as shown in the figure.When the SDI ranges from 0.4 to 0.6, the disease burden rises significantly, followed by another increase when SDI exceeds 0.7. This suggests that bipolar disorder risk fluctuates in middle-to-low and high SDI ranges, potentially reflecting differences in diagnostic and treatment strategies across economic levels.\u003c/p\u003e\n\u003cp\u003eThe DALYs of depression (Figure 7C) show a weak negative correlation with SDI (\u0026rho; = -0.08, P = 0.010), while its incidence rate (Figure 7G) has a positive correlation (\u0026rho; = 0.44, P \u0026lt; 0.001). This discrepancy suggests that in high-SDI regions, despite a higher incidence of depression, the overall disease burden may be reduced due to more advanced diagnosis, intervention, and treatment strategies. In contrast, in low-SDI regions, limited resources and inadequate early interventions may explain the smaller gap in overall disease burden. However, the reversed trend in incidence rate emphasizes the need for increased attention to low-income female populations.\u003c/p\u003e\n\u003cp\u003eThe DALYs (Figure 7D) and incidence rate (Figure 7H) of schizophrenia follow a \"U\"-shaped trend: the disease burden is lowest when SDI is around 0.6 but increases significantly at both lower and higher SDI levels. This pattern may result from structural factors such as social resource allocation, healthcare accessibility, and treatment adherence in schizophrenia.\u003c/p\u003e\n\u003cp\u003eOverall, the data highlight the \"dual acceleration\" of global mental health inequality\u0026mdash;high disease burden in low-income populations and imbalanced health resources in high-SDI regions, limiting their ability to reduce the burden of certain mental disorders. This trend is most evident in anxiety disorders and schizophrenia, emphasizing the need to strengthen mental health systems in low-SDI regions, improve early interventions, and optimize resource allocation.\u003c/p\u003e\n\u003cp\u003eAnalysis of Health Inequities in Depression, Anxiety Disorders, Bipolar Disorder, and Schizophrenia Among Women of Reproductive Age Worldwide\u003c/p\u003e\n\u003cp\u003eHealth inequalities in global mental health are becoming more pronounced due to uneven socioeconomic development. This study analyzes DALYs and incidence data to examine four major mental disorders: schizophrenia, bipolar disorder, depression, and anxiety. The Concentration Index (CI) and Slope Index of Inequality (SII) are used to quantify relative and absolute health inequalities (Online Supplementary Figures 1 and 2). Overall, SII indices for all four disorders have risen, while CI indices have declined, reflecting growing disparities in disease burden across socioeconomic strata. Health inequality in anxiety disorders has worsened significantly, with the SII for incidence and DALYs increasing from 278.61 and 196.96 to 432.21 and 330.90, respectively, indicating a rising disease burden among low-income populations. The burden of schizophrenia has shifted toward lower socioeconomic groups, with the DALYs SII rebounding from -842.74 to 465.39. The incidence SII of depression rose from -138.47 to 39.84, while the DALYs gap slightly narrowed. Inequality in bipolar disorder remained stable; however, the disease burden persisted among low-income groups, with the DALYs SII steadily increasing.\u003c/p\u003e\n\u003cp\u003eThe CI indices for all four disorders have uniformly declined, indicating a growing distortion in the distribution of disease burden across the socioeconomic spectrum over time. This trend signals a widening global mental health inequality gap, particularly in low-SDI regions, where the burden is escalating at an alarming rate. Urgent action is needed from the international community, national governments, and health institutions to strengthen mental health service frameworks and optimize resource allocation in low-SDI regions. TThese efforts are essential to supporting vulnerable populations with mental disorders and ensuring equitable, accessible mental healthcare.\u003c/p\u003e\n\u003cp\u003eProjection Analysis of Depression, Anxiety Disorders, Bipolar Disorder, and Schizophrenia Among Women of Reproductive Age Worldwide Until 2035\u003c/p\u003e\n\u003cp\u003eProjections based on the GBD database (Online Supplementary Figures 3) suggest that the disease burden and incidence rates of anxiety disorders and depression among women of reproductive age will significantly increase over the next decade, with this trend accelerating after 2030. This indicates that anxiety disorders and depression may present a greater public health challenge in the future. In contrast, while bipolar disorder and schizophrenia show an upward trend, their growth rates remain moderate. Specifically, both the total DALYs and age-standardized rates for anxiety disorders and depression show a continuous upward trend. The DALYs for anxiety disorders have steadily increased from 1990 to 2020 and are projected to surge dramatically by 2035, with a similar upward trend in age-standardized rates. Similarly, the total DALYs and age-standardized rates for depression have steadily increased, with a more pronounced rise expected in the coming years. In comparison, while the total DALYs and age-standardized rates for bipolar disorder and schizophrenia have increased, their growth has been gradual. DALYs for bipolar disorder have followed a moderate upward trend from 1990 to 2020 and are expected to continue this trajectory through 2035. Similarly, the DALYs and age-standardized rates for schizophrenia exhibit a similar pattern of slow growth.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003eMain findings\u003c/h2\u003e\u003cp\u003eThis study, based on GBD 2021 data, systematically analyzed the evolution of the disease burden of depression, anxiety disorders, bipolar disorder, and schizophrenia among women of reproductive age worldwide from 1990 to 2021.\u003c/p\u003e\u003cp\u003eKey findings include:(1) Globally, the burden of depression and anxiety disorders among women of reproductive age has continued to increase, whereas the prevalence of bipolar disorder and schizophrenia has remained relatively stable. The total number of cases of depression and anxiety disorders has risen significantly, while the incidence rates of schizophrenia and bipolar disorder have shown minimal changes. (2) Age-specific analyses indicate that the burden of depression and anxiety disorders is highest among women aged 25\u0026ndash;34, whereas bipolar disorder peaks in the 15\u0026ndash;19 age group, and schizophrenia is most prevalent among women aged 20\u0026ndash;24. The disability-adjusted life years (DALYs) associated with depression and anxiety disorders have increased most rapidly among women over 40, suggesting that the health burden of mental disorders is particularly severe during midlife in women of reproductive age. (3) Regionally, high-income countries exhibit the highest burden of depression and anxiety disorders, while low-income countries have seen a more rapid increase in the burden of schizophrenia and bipolar disorder. The burden of depression and anxiety has decreased in East Asia and South Asia, while anxiety disorders have increased most significantly in tropical Latin America and Central America. (4) The relationship between SDI (socio-demographic index) levels and the burden of mental disorders is complex. In high-SDI countries, the burden of depression and anxiety disorders has significantly increased, while the burden of schizophrenia follows a \"U-shaped\" pattern, with the lowest burden in regions with moderate SDI and higher burdens in both low-SDI and high-SDI regions.(5) Countries affected by social unrest and conflict, such as Yemen, South Sudan, and Palestine, have a much higher burden of anxiety disorders compared to the global average. In some countries, such as Bolivia and Lebanon, the burden of depression and anxiety disorders has increased significantly over the past 30 years, highlighting the critical role of socio-economic factors in the prevalence of mental disorders.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eReasons for Age-related Differences\u003c/h3\u003e\n\u003cp\u003eThe age-related differences in mental disorders are primarily influenced by physiological changes, social role transitions, and psychological stress\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e.The burden of bipolar disorder is highest among females aged 15\u0026ndash;19, related to an immature emotional regulation system, unstable neurotransmitter functions, and social conflicts and academic pressures typical of adolescence and the rebellious phase \u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e.Schizophrenia is most common among women aged 20\u0026ndash;24, the typical onset age for the disorder. Genetic susceptibility, chronic stress during adolescence, and changes in the university or workplace environment may be key contributing factors \u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe burden of depression and anxiety disorders is highest among women aged 25\u0026ndash;34, a stage during which women typically face career pressures, increased family responsibilities, and the physiological and psychological changes associated with childbirth and child-rearing\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e. Additionally, workplace gender discrimination and societal expectations in certain regions may further exacerbate the psychological burden on women \u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e.The burden of depression and anxiety disorders significantly increases among women over 40, which may be associated with the decline in estrogen levels, emotional instability due to menopausal hormonal fluctuations \u003csup\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e, reduced social support during the empty nest phase, and the accumulation of long-term psychological stress.\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eReasons for Differences Across Countries and Regions\u003c/h2\u003e\u003cp\u003eThe differences in the burden of mental disorders across countries are primarily influenced by the level of economic development, healthcare resource allocation, social culture, and public health policies \u003csup\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e.High-income countries (e.g., North America, Western Europe) have the highest burden of depression and anxiety disorders, which may be due to the higher rates of mental health disorder recognition and healthcare access in these regions \u003csup\u003e[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/sup\u003e. Additionally, intense social competition, increased living costs, and high work-related stress have contributed to the rising incidence of depression and anxiety.Furthermore, the acceleration of urbanization, along with the increasing sense of alienation and loneliness in social relationships, may further exacerbate the incidence of anxiety and depression.The burden of schizophrenia and bipolar disorder has grown more rapidly in low-income countries, which may be attributed to a lack of healthcare resources that results in delayed diagnosis and treatment \u003csup\u003e[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/sup\u003e, thereby worsening the condition.Additionally, the stigma surrounding mental disorders is more pronounced, leading to long-term disability in patients who often lack treatment, thereby increasing the disease burden \u003csup\u003e[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/sup\u003e.The increasing burden of schizophrenia in sub-Saharan Africa and certain South Asian countries may also be associated with factors such as malnutrition, perinatal infections, and early childhood trauma.In socially unstable regions, such as Yemen, South Sudan, and Palestine, the burden of anxiety disorders is much higher than the global average. These countries have been in a prolonged state of war and social unrest, with large-scale population displacement, economic depression, and the collapse of social support systems. A large portion of the population has experienced traumatic events and post-traumatic stress disorder (PTSD), contributing to the high prevalence of anxiety and depression disorders\u003csup\u003e[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eDifferences in the Burden Across Different Types of Mental Disorders\u003c/h2\u003e\u003cp\u003eThe burden differences across various types of mental disorders are influenced by a combination of biological, environmental, and social factors \u003csup\u003e[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]\u003c/sup\u003e.The burden of depression and anxiety disorders has increased rapidly, which may be related to global economic instability, intensified social competition, information overload (e.g., the widespread use of social media), and changes in lifestyle (e.g., sedentary behavior and lack of physical activity).Additionally, the physiological and psychological challenges women face during periods of social role transitions (e.g., marriage, childbirth, menopause) may further exacerbate symptoms of anxiety and depression.In contrast, the burden of schizophrenia and bipolar disorder remains relatively stable, primarily influenced by genetic factors, with less impact from socio-economic changes on their incidence.However, in low- and middle-income countries, the limited availability of healthcare resources and insufficient social support systems may result in longer disease courses for patients, leading to higher DALYs.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eInnovations and Highlights of the Study\u003c/h2\u003e\u003cp\u003eThe main innovations of this study are: (1) For the first time, a comprehensive analysis of the global disease burden of four major mental disorders among women of reproductive age (15\u0026ndash;49 years) is conducted based on the GBD 2021 data, with long-term trend analysis incorporating age, region, and SDI stratification.(2) The use of the Slope Index of Inequality (SII) reveals that the burden of anxiety disorders is accelerating in lower-income groups (with a 55% increase in the slope from 1990 to 2021), providing a target for mental health policies aimed at \"precise poverty alleviation.\"(3) The study identifies key changing trends in the burden of mental disorders among women across different age groups, emphasizing the mental health risks faced by women of reproductive age during career development, childbirth, and social role transitions.(4) A disease burden model for 2035 is developed, warning that the burden of anxiety and depression will continue to rise. The study calls for proactive planning of digital interventions (such as AI-assisted diagnosis) and integrated perinatal mental health services.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eLimitations of the Study\u003c/h2\u003e\u003cp\u003eDespite the extensive data coverage and long time span of this study, certain limitations remain: (1) The study does not analyze specific subtypes of depression, anxiety disorders, bipolar disorder, and schizophrenia, such as major depressive disorder and persistent depressive disorder. This omission may impact the accuracy of the burden assessment for different disease subtypes. (2) The GBD estimates may underestimate the actual burden in conflict zones (e.g., Yemen) or culturally restrictive regions (e.g., conservative religious communities) due to model dependencies and data gaps. This is particularly true for diseases with high diagnostic heterogeneity, such as bipolar disorder. (3) The study does not consider gender roles (e.g., caregiving burdens) or the impact of religious beliefs on treatment adherence. This omission may result in an underestimation of the influence of socio-cultural factors on disease trajectories.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003eFuture Directions of the Study\u003c/h2\u003e\u003cp\u003eThe mental health crisis among women of reproductive age is a major challenge in global public health in the 21st century. Based on the study's findings, future actions should focus on three areas: Policy Level, Research Directions, and Social Aspects. In high-SDI regions, it is crucial to promote workplace mental health legislation (e.g., mandatory mental health leave) and integrate mental health services into maternal healthcare systems. In low-SDI regions, the focus should be on expanding service coverage through \"mobile clinics\" and training community health workers, with a priority on post-trauma interventions in conflict areas. Global collaboration is essential to establish a cross-national mental health monitoring network and implement cross-lifecycle interventions during key windows, such as 25\u0026ndash;34 years and 45\u0026ndash;49 years. Research Directions: Employ multi-omics technologies to analyze the \"social adversity-epigenetics-mental illness\" pathway and explore the molecular mechanisms behind the \"slope reversal\" of depression in low-income groups. Evaluate cases such as China's \"Internet\u0026thinsp;+\u0026thinsp;Mental Health\" model and Nordic welfare policies, extracting intervention strategies adaptable to different cultural contexts. Social Aspects: The stigma surrounding mental illness should be dismantled, and mental health education should be integrated into basic education curricula, with particular attention to healthcare barriers faced by male anxiety disorder patients. Through interdisciplinary collaboration and data-driven precision strategies, the global community can build a more resilient mental health support system for women of reproductive age, particularly under the dual pressures of aging and urbanization.\u003c/p\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is a secondary analysis based on publicly available data from the Global Burden of Disease (GBD) 2021 database, provided by the Institute for Health Metrics and Evaluation (IHME). All data are anonymized and aggregated, with no individual-level or identifiable information involved. Therefore, ethical approval and informed consent were not required.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed during the current study are publicly available in the Global Burden of Disease (GBD) repository, which can be accessed at:https://vizhub.healthdata.org/gbd-results/.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData sharing statement\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe data used for the analyses is available by email request to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of anycommercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the following funding sources:\u003c/p\u003e\n\u003cp\u003eNatural Science Foundation of Henan Province(242300421307);\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHenan Collaborative Innovation Center of Prevention and Treatment of Mental Disorders(XTkf11);\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHenan Provincial Key Research and Development Special Project2025（251111520600）;\u003c/p\u003e\n\u003cp\u003eNational Natural Science Foundation of China (82374273);\u003c/p\u003e\n\u003cp\u003eKey issues of education and teaching reform in Henan province（2024SJGLX0141）.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was led by Junqiang Zhao, with Junyao Li responsible for the overall design, data analysis, and manuscript writing. Bo Song, Min Cai, and Wanqi Sun provided data analysis and methodological support. Luping Wang were responsible for language editing and formatting. Shichang Yang and Xiaohong Kang provided expert opinions, assisting in the interpretation of the clinical significance of the mental disorders burden, and participated in the review of the manuscript structure. All authors made significant contributions to the successful completion of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe sincerely acknowledge the Global Burden of Disease (GBD) Study for providing open-access data that contributed to this research. We are deeply grateful to Prof. Junqiang Zhao, Prof. Shichang Yang, and Prof. Xiaohong Kang for their invaluable guidance and insightful suggestions throughout the study. Their expertise and continuous support have played a crucial role in the development of this research.\u003c/p\u003e\n\u003cp\u003eAdditionally, this study was supported by the Natural Science Foundation of Henan Province (Grant No. 242300421307), the Henan Collaborative Innovation Center of Prevention and Treatment of Mental Disorders (Grant No. XTkf11), the Henan Provincial Key Research and Development Special Project 2025 (Grant No. 251111520600), the National Natural Science Foundation of China (Grant No. 82374273), and the Key Issues of Education and Teaching Reform in Henan Province (Grant No. 2024SJGLX0141). We sincerely appreciate the financial support provided by these institutions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePublisher’s note\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Any product evaluated in this article or claim made by its manufacturer is not guaranteed or endorsed by the publisher.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGlobal regional. and national burden of 12 mental disorders in 204 countries and territories, 1990\u0026ndash;2019: a systematic analysis for the Global Burden of Disease Study 2019 [J]. Lancet Psychiatry, 2022, 9(2): 137\u0026ndash;150.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGlobal regional. national burden of disorders affecting the nervous system, 1990\u0026ndash;2021: a systematic analysis for the Global Burden of Disease Study 2021 [J]. Lancet Neurol. 2024;23(4):344\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFREEMAN M. The World Mental Health Report: transforming mental health for all [J]. 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Lancet. 2022;400(10361):1438\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBYATT N, BRENCKLE L, SANKARAN P, et al. Effectiveness of two systems-level interventions to address perinatal depression in obstetric settings (PRISM): an active-controlled cluster-randomised trial [J]. Lancet Public Health. 2024;9(1):e35\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMURRAY C J. The global burden of disease study at 30 years [J]. Nat Med. 2022;28(10):2019\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBARIBAULT B, COLLINS A G E. Troubleshooting Bayesian cognitive models [J]. Psychol Methods. 2025;30(1):128\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCOLLABORATORS G B O D. S. Global burden of disease study 2021 (GBD 2021) results [Z]. 2021.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNATIONS U. World Population Prospects 2019: Highlights [M]. United Nations; 2019.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLIU Z, JIANG Y, YUAN H, et al. The trends in incidence of primary liver cancer caused by specific etiologies: Results from the Global Burden of Disease Study 2016 and implications for liver cancer prevention [J]. J Hepatol. 2019;70(4):674\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKRISTENSEN S M, LARSEN T M B, URKE H B, et al. Academic Stress, Academic Self-efficacy, and Psychological Distress: A Moderated Mediation of Within-person Effects [J]. J Youth Adolesc. 2023;52(7):1512\u0026ndash;29.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCOSGROVE V E, ROYBAL D, CHANG K D. Bipolar depression in pediatric populations: epidemiology and management [J]. Paediatr Drugs, 2013, 15(2): 83\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWALDER D J, FARAONE S V, GLATT S J, et al. Genetic liability, prenatal health, stress and family environment: risk factors in the Harvard Adolescent Family High Risk for schizophrenia study [J]. Schizophr Res. 2014;157(1\u0026ndash;3):142\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZHOU B, WU X, GE R, et al. Career women's mental wellbeing in the era of population decline: the effects of working environment and family environment on the mental wellbeing [J]. Front Public Health. 2024;12:1462179.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHEISE L, GREENE M E, OPPER N, et al. Gender inequality and restrictive gender norms: framing the challenges to health [J]. Lancet. 2019;393(10189):2440\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCLAYTON A H, NINAN PT. Depression or menopause? Presentation and management of major depressive disorder in perimenopausal and postmenopausal women [J]. Volume 12. The Primary Care Companion for CNS Disorders; 2010. p. 26233. 1.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTHORNICROFT G, DEB T. Community mental health care worldwide: current status and further developments [J]. World Psychiatry. 2016;15(3):276\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRATHOD S, PINNINTI N, IRFAN M, et al. Mental health service provision in low-and middle-income countries [J]. Health Serv insights. 2017;10:1178632917694350.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eESPONDA G M, HARTMAN S, QURESHI O, et al. Barriers and facilitators of mental health programmes in primary care in low-income and middle-income countries [J]. Lancet Psychiatry. 2020;7(1):78\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDA SILVA A G, BALDA\u0026ccedil;ARA L. The impact of mental illness stigma on psychiatric emergencies [J]. Front Psychiatry. 2020;11:573.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJAVIDI H. YADOLLAHIE M. Post-traumatic stress disorder [J]. 2012.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBELFIORE C I, GALOFARO V. A Multi-Level Analysis of Biological, Social, and Psychological Determinants of Substance Use Disorder and Co-Occurring Mental Health Outcomes [J]. Psychoactives. 2024;3(2):194\u0026ndash;214.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bpsy","sideBox":"Learn more about [BMC Psychiatry](http://bmcpsychiatry.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bpsy/default.aspx","title":"BMC Psychiatry","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Women of reproductive age, Mental disorders, Disease burden, Incidence rate, DALYs","lastPublishedDoi":"10.21203/rs.3.rs-6678574/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6678574/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground：\u003c/strong\u003eMental disorders are a significant global health concern recognized by the World Health Organization (WHO). They contribute substantially to the disease burden and are strongly associated with high suicide rates.Depression, anxiety, bipolar disorder, and schizophrenia are among the most prevalent mental illnesses, severely affecting cognitive function, emotional regulation, and social interaction.Women of reproductive age (15–49 years) encounter distinct physiological and psychological challenges, rendering them more susceptible to stress. This heightened vulnerability elevates their risk of pregnancy-related complications, maternal and infant health issues, and neurodegenerative diseases.Furthermore, socioeconomic stress, gender role expectations, reproductive factors, and restricted access to healthcare collectively exacerbate their vulnerability to mental disorders.However, comprehensive evaluations of the long-term mental health burden in this population remain scarce.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAims：\u003c/strong\u003eThis study aims to quantify the global disease burden of depression, anxiety, bipolar disorder, and schizophrenia in women of reproductive age from 1990 to 2021, using GBD 2021 data. It will analyze their spatiotemporal distribution, assess the impact of the Sociodemographic Index (SDI) on disease burden, and provide evidence to support the development of targeted prevention and control strategies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods：\u003c/strong\u003eBayesian meta-regression was applied to calculate age-standardized rates (ASIR) and Disability-Adjusted Life Years (DALYs) using GBD 2021 standardized data.The data were stratified based on GBD standards into 7 age subgroups (15–49 years), 21 geographical regions, and 5 SDI levels.The Joinpoint regression model was used to estimate the annual percent change (EAPC, 95% UI).Statistical analysis was performed using R software.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults：\u003c/strong\u003eFrom 1990 to 2021, depression and anxiety in women of reproductive age showed a continuous global increase.Anxiety-related DALYs rose from 9.3 million (95% UI: 5.9–13.6) to 16.4 million (95% UI: 10.4–24.0, EAPC = 0.16).In high-income regions, such as North America (EAPC = 0.64), the age-standardized death rate (ASDR) for depression rose from 948.86/100,000 to 1,073.5/100,000.The ASDR for bipolar disorder remained stable, while schizophrenia showed a slight negative trend (EAPC = -0.02).High SDI regions displayed a polarized burden of anxiety and depression, with North America having the highest depression ASDR at 1,929.21/100,000, while low SDI regions saw a significant increase in schizophrenia-related DALYs.Age-stratified analysis revealed that the burden of bipolar disorder was highest in the 15–19 age group, schizophrenia in the 20–24 age group, and depression and anxiety in the 25–34 age group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions：\u003c/strong\u003eDepression and anxiety are the primary mental health threats for women of reproductive age, with a particularly pronounced disease polarization effect in high-income regions.Therefore, targeted interventions are urgently needed to reduce socioeconomic disparities, improve perinatal mental health services, and prioritize resource allocation to conflict-affected and low SDI regions.Policymakers should integrate mental health into maternal healthcare systems and use digital tools to reduce the risk of long-term disability.\u003c/p\u003e","manuscriptTitle":"Global Burden of Mental Disorders in Women of Reproductive Age from 1990 to 2021: A Comprehensive Analysis and Trend Prediction of Depression, Anxiety, Bipolar Disorder, and Schizophrenia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-10 06:26:14","doi":"10.21203/rs.3.rs-6678574/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-07-04T16:13:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"165335281207874766971582769054716387975","date":"2025-07-04T10:46:11+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-04T10:39:32+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-05-22T19:13:35+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-19T04:50:45+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-19T04:49:10+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Psychiatry","date":"2025-05-16T07:57:01+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bpsy","sideBox":"Learn more about [BMC Psychiatry](http://bmcpsychiatry.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bpsy/default.aspx","title":"BMC Psychiatry","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"388a54bb-a513-4b1d-9967-e560b2001a57","owner":[],"postedDate":"July 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-07-10T06:26:14+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-10 06:26:14","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6678574","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6678574","identity":"rs-6678574","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}