Trends and burden of schizophrenia in Asia: Insights from the global burden of disease study 2021

Trends and burden of schizophrenia in Asia: Insights from the global burden of disease study 2021 | 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 Trends and burden of schizophrenia in Asia: Insights from the global burden of disease study 2021 Yuanjun Xie, Tian Zhang, Naiting He, Junxin Zhou, Guangcai Chen, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6476890/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objectives Schizophrenia is a severe mental disorder imposing a substantial burden worldwide. Understanding its impacts and trends in Asia is crucial for devising effective intervention. This study quantified the prevalence, incidence, and years lived with disability (YLDs) rates of schizophrenia across Asian regions, examine their trends, and explore the relationship between socio-demographic index (SDI) and YLDs rates. Methods Data from Global Burden of Disease (GBD) study (1990–2021) were analyzed by age, sex, region, and SDI levels. Age-standardized YLDs rates were assessed using the estimated annual percentage change (EAPC), while future trends were forecasted using the Bayesian age-period-cohort (BAPC) model. The correlation between age-standardized YLD rates and SDI was also examined. Results Schizophrenia prevalence in Asia rose from 8.42 million cases in 1990 to 14.96 million in 2021, with higher rates in males. Incidence increased by 32.76%, and in 2021 schizophrenia accounted for 5.45 million YLDs, peaking in aged 35–39 years. Vietnam reported the highest age-standardized YLD rates, followed by China, Taiwan, and the Maldives. EPAC trends indicated rising burdens in Myanmar and the Maldives, while declines occurred in North Korea and Pakistan. A positive correlation between the SDI levels and age-standardized YLD rates was identified, with forecasts predicting a continued rise in schizophrenia-related YLDs in Asia over the next three decades. Conclusion The burden of schizophrenia in Asia has grown markedly over the past three decades. Urgent evidence-based policies are needed to improve early detection, ensure equitable access to mental healthcare, and reduce regional disparities. Schizophrenia Burden of disease Asia Prevalence Incidence Years lived with disability Socio-demographic Index Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 1. Introduction Schizophrenia is a severe and life-long mental health disorder, typically emerges in late adolescence and early adulthood [ 1 ], affects roughly one percent of the population [ 2 ]. This disease is usually characterized by three categories of symptoms, including positive symptoms (e.g., hallucinations and delusion), negative symptoms (e.g., apathy and avolition ), and cognitive impairments (e.g., problems with memory and attention) [ 3 ]. Although it affects a minority of the global population, it profound impact on quality of life [ 4 ], and induces extensive social functioning and employment problems [ 5 , 6 ]. Schizophrenia is associated with a significantly reduced life expectancy, averaging approximately 14.5 years shorter than the general population, with men experiencing a greater reduction than women [ 7 ]. In addition to an unhealthy lifestyle exacerbated by low income and limited access to healthcare [ 8 ], physical comorbidity and increased inflammation may also contribute to the observed decrease in life expectancy [ 9 ]. Unnatural causes, such as suicide, contribute to less than 15% of the excess deaths [ 10 ]. The peak prevalence and disability burden are observed around the age of 35 years in both sexes [ 11 ]. Additionally, the disease is disproportionately higher in low- and middle-income countries, reaching up to four times that observed in high-income regions [ 12 ]. Despite the significant burden of schizophrenia, public health efforts remain constrained by insufficient data on the geographic and temporal variations of the disease. Understanding the epidemiological trends of schizophrenia is critical for optimizing resource allocation and developing targeted interventions to mitigate its impact. The Global Burden of Disease (GBD) study provides a comprehensive framework for analyzing the prevalence, incidence, and burden of medical disorders, including mental disorders and schizophrenia across diverse regions and demographic groups. First quantified in 1990 by the World Health Organization in 1990 [ 13 ], the GBD study has since evolved significantly. The most recent iterations, GBD 2021, carried out by the Institute for Health Metrics and Evaluation (IHME) at the University of Washington[ 14 ], incorporates notable methodological advancements. Previous studies have reported on the GBD estimates of schizophrenia, highlighting its global prevalence, incidence, or burden [ 12 , 15 , 16 ]. For instance, 2016 GBD data revealed that the raw prevalence of schizophrenia increased from over 13 million cases in 1990 to nearly 21 million cases by 2016 [ 12 ], and this disorder accounted for approximately 13 million years of life lived with disability, underscoring its significant contribution to the global burden of disease. However, there is a notable lack of comprehensive, detailed findings specifically addressing the burden of schizophrenia in Asia. This study aimed to address this gap by reporting on the epidemiological trends and disease burden of schizophrenia in Asian countries and territories between 1990 to 2021 based on GBD 2021 data. Furthermore, the analyses of the association between schizophrenia burden and the sociodemographic index (SDI) as well as predictions regarding this disease burden were performed to provide insights into patters of schizophrenia burden across different regions. 2. Matherials and Methods 2.1. Data source The data utilized in this study is available on GBD database (1990–2021) ( http://ghdx.healthdata.org ). GBD is an international collaborative initiative dedicated to providing a comprehensive overview of the current state of diseases worldwide and is recognized as one of the most comprehensive and systematic global epidemiological efforts [ 17 ]. The GBD framework enables comparative assessments of prevalence, incidence, mortality, and YLDs estimates. The dataset comprises annual data for the world, Asia, and 49 Asian countries and territories. The prevalence, incidence, and YLDs estimates were extracted in cases and rates, stratified by region, countries, territory, age, and sex. Additionally, age-standardized YLDs rates were calculated using the GBD world population standard to ensure comparability across populations. All estimates are reported as numbers and rates per 100,000 population, accompanied by 95% uncertainty intervals (UI)[ 18 ]. Each step used in this study to analyze the GBD database was consistent with the Guidelines for Accurate and Transparent Health Estimates Reporting, which has been described in detail previously [ 19 ]. 2.2 Case definition Schizophrenia is defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria (DSM-IV-TR: 295.10-295.30, 295.60, 295.90) or the International Classification of Diseases (ICD) criteria (ICD-10: F20), as detailed under the GBD classification code B.6.1. The diagnostic criteria included the following several key elements[ 18 ]:(1) the present of at least two of the following symptoms for a significant portion of a one-month period: delusion, hallucinations, disorganized speech, markedly disorganized or catatonic behavior, and negative symptoms; (2) significant dysfunction in social or occupational functioning;(3) the persistence of signs and symptoms for at least six months;(4) the exclusion of alternative causes, such as substance use, schizoaffective or mood disorders, general medical conditions, or a connection to pervasive developmental disorders. 2.3 Sociodemographic index The burden of schizophrenia was evaluated in relation to national development levels, as measured by the socio-demographic Index (SDI)[ 20 ]. The SDI is a composite indicator of development status as it pertains to health outcomes, ranges from 0 to 1, with higher values indicating higher socioeconomic development. For Asian countries and territories, SDI values were categorized into five distinct quintiles: low SDI (< 0.45), low-middle SDI (≥ 0.45 and < 0.61), middle SDI (≥ 0.61 and < 0.69), high-middle SDI (≥ 0.69 and < 0.80), and high SDI (≥ 0.80). 2.4. Statistical analysis Prevalence, Incidence, and YLDs rates were calculated per 100,000 population according to the GBD database statistics. Trends in disease burden (YLDs) were assessed based on the average annual percentage change (EAPC). The calculation of EAPC and its confidence intervals (CI) were based on a log-transformed linear regression model during a specified period[ 21 ]. An EAPC value and the lower limit of its 95% CI greater than 0 indicate an increasing trend for the corresponding indicator (e.g., YLDs). Conversely, an EAPC value and the upper limit of its 95% CI less than 0 indicate a decreasing trend for the corresponding indicator (e.g., YLDs). The Bayesian age-period-cohort (BAPC) model was applied to forecast the future change in the burden of schizophrenia in 2050. The BAPC model addresses the parameter estimation challenges arising from the linear relationship between age, period, and cohort by incorporating Bayesian priors and using the Integrated Nested Laplace Approximation (INLA) algorithm[ 22 ]. All statistical analyses were performed using R (version 4.4.2; https://www.r-project.org ). 3. Results 3.1. Global Trends In Asia, there has been a consistent increase in prevalence, incidence, and YLDs due to schizophrenia from 1990 to 2021 (Fig. 1 and Table 1 ). Specifically, the prevalence cases of schizophrenia showed a steady increase, rising from approximately 8.42 million (95%UI:9.91–7.03) in 1990 to nearly 14.96 million (95%UI:12.56–17.54) in 2021. Throughout this period, the prevalence was consistently higher in males compared to females. The number of prevalent cases among males rose from approximately 4.60 million (95%UI:3.83–5.43) in 1990 to around 8.11 million (6.80–9.54) in 2021, with an increase of 76.30%; while females saw an increase from 3.82 million (95%UI: 3.19–4.50) to approximately 6.85 million (95%UI:5.75–8.01) over the same period, with an increase of 79.32%. Similarly, in 2021, there were 0.77 million incidence cases of schizophrenia reported in Asian, reflecting a 32.76% increase since 1990. The incidence among males was consistently higher than among females, with 0.43 million cases (95UI:0.36–0.52) reported in males and 0.34 million cases (95%UI:0.28–0.41) in female. Notably, the increase in incidence was greater for males compared to female, with growth rates of 34.38% and 30.77%, respectively, between 1990 to 2021. In addition, in 2021, schizophrenia accounted for 5.45 million YLDs in Asia. Males contributed a larger portion of these YLDs, representing approximately 55.23% of the total. The YLD rate per 100,000 people for schizophrenia in Asia showed an increasing trend, rising from 171.70 (95% UI: 127.83–219.6) in 1990 to 208.07 (95% UI: 154.45-266.72) in 2021. Table 1 prevalence, incidence, and YLDs in schizophrenia from 1990 to 2021 Prevalence (million,95%UI) Incidence (million,95%UI) YLDs (million,95%UI) 1990 2021 1990 2021 1990 2021 Both 8.42(9.91–7.03) 14.96(12.56–17.54) 0.58(0.47–0.68) 0.77(0.64–0.93) 5.45(4.59–6.97) 9.62(7.14–12.33) Male 4.60(3.83–5.43) 8.11(6.80–9.54) 0.32(0.26–0.38) 0.43(0.36–0.52) 3.01(2.23–3.84) 5.28(3.92–6.77) Female 3.82(3.19–4.50) 6.85(5.75–8.01) 0.26(0.21–0.31) 0.34(0.28–0.41) 2.44(1.83–3.13) 4.34(3.22–5.55) 3.2 Age and sex effects The age and sex-specific burden of schizophrenia in Asia, as depicted in Fig. 2 , revealed distinct age-related variation. The age-standardized YLDs rate progressively increased from early adolescence, reaching its peak in the 35–39 years age group (Fig. 2 a). In addition, the rate was generally higher in males than in females across most age ranges (Fig. 2 b), except for the oldest age groups, such as those aged above 85 years. 3.3 Disease burden by country In 1990, the countries and territories with the highest age-standardized YLDs rate (per 100,000) for schizophrenia in Asia were predominantly located in East and Southeast (Fig. 3 a). Vietnam reported the highest rate at 1991.16 (95%UI:138.30-270.05), followed by China at 195.67 (95%UI:147.78-244.07), Taiwan at 135.34 (95%UI:135.34-257.68), and Malaysia at 189.04 (95%UI:133.04-266.36). By 2021, the burden of schizophrenia remained significant (Fig. 3 b), with Vietnam still having the highest age-standardized YLDs rate (209.00; 95%UI:148.09-283.33), followed by China (203.88; 95%UI:152.53-255.67), Taiwan (202.09; 95%UI:143.27-277.15), and the Maldives (200.74; 95%UI:143.69-272.62). Over the three decades, the EAPC analysis revealed heterogeneous trends in the schizophrenia burden across Asia (Fig. 3 c). Myanmar (+ 0.31; 95%CI:0.27–0.36), Maldives (+ 0.27; 95%CI:0.22–0.31), and Laos (+ 0.26; 95%CI:0.22–0.29) exhibited the most notable increase in the burden of schizophrenia. In contrast, North Korea (-0.16; 95%CI: -0.17 to -0.14), the United Arab Emirates (-0.12; 95%CI: -0.13 to -0.11), and Pakistan (-0.08; 95%CI:-0.09 to -0.07) exhibited the largest declines. 3.4 Relationship between disease burden and SDI levels The relationship between age-standardized YLDs rates and SDI level for each country was presented in Fig. 5 . It turned out that there was a significant association between burden estimates of schizophrenia and SDI levels for each country in Asia during the observation period. Regions with higher SDI levels tend to have higher age-standardized YLDs rates for schizophrenia. For example, high-SDI regions like Japan exhibit some of the highest YLD rates, while low-SDI regions, such as Afghanistan, show consistently lower rates. However, the variation within SDI levels is notable, as certain regions like Bhutan, Pakistan, and India deviate from the general trend, displaying relatively high YLD rates despite lower SDI rankings. 3.5 Prediction of disease burden As illustrated in Fig. 4 , the YLDs rates among the Asia and the selected largest population countries, namely China, India, and Indonesia remained relative stable, and slowly increasing trend historically. The overall trend of increasing YLDs rate in Asia and these selected countries are predicted to continue for the further 30 years. 4. Discussion The present study investigated the trend and burden of schizophrenia in Asia using GBD data 2021. The findings revealed the growing burden of schizophrenia, with increases in prevalence, incidence, and YLDs. Prevalence rose from 8.42 million cases in 1990 to 14.96 million in 2021, with males consistently exhibiting higher rates. Incidence grew by 32.76%, also with greater increases in males. In 2021, schizophrenia caused 5.45 million YLDs, peaking in middle adulthood (35–39 years) and higher in males. Vietnam had the highest age-standardized YLD rates, followed by China, Taiwan, and the Maldives. Over time, some countries like Myanmar and Maldives, experienced increases, while others, such as North Korea and Pakistan, saw declines. Higher SDI levels were linked to higher YLD rates, although exceptions were observed. Projections indicate continued increases in schizophrenia-related YLDs over the next three decades. Key trends in schizophrenia burden Over the past three decades, the prevalence, incidence, and YLDs rate attributable to schizophrenia have shown a consistent upward trajectory[ 23 ], with Asia experiencing the most pronounced rise. This pattern underscores the growing public health challenge posed by this severe mental disorder, particularly in regions undergoing rapid demographic shifts and epidemiological transitions. Socioeconomic factors appear to play a critical role in driving these trends. Urbanization, for instance, has been associated with a heightened risk of schizophrenia, attributed to factors such as increased social stress, exposure to environmental pollutants, and the weakening of social support networks. These dynamics have contributed to the rising prevalence and incidence of the disorder[ 24 , 25 ]. Concurrently, demographic changes, such as population growth and aging, have further exacerbated the disease burden [ 26 , 27 ], particularly in Asia. As global life expectancy continues to increase alongside with financial development [ 28 ], greater healthcare budget allocation, the adoption of clean and sustainable technology [ 29 ], the protracted duration of chronic mental disorders like schizophrenia has further intensified the cumulative burden. Globally, the burden of schizophrenia remains disproportionately higher among males than females[ 30 ]. Males tend to exhibit a greater vulnerability to an earlier age of onset and severe symptomatology[ 31 ], consistent with previous research attributing these disparities to confluence of genetic, neurodevelopmental, and hormonal influences[ 32 ]. For instance, estrogen is postulated to play a neuroprotective role in mitigating schizophrenia pathology in women[ 33 ]. Additionally, in some societies, social factors such as the stigma associated with mental illness, may exacerbate this burden by limiting healthcare access among males[ 34 ], who are generally less likely to seek mental health treatment compared to females. These changes are further compounded by the complexity associated with aging populations [ 28 ], including gender-specific survival rates, patterns of comorbidities, and shifts in demographic structures, all of which influence observed trends in the burden of schizophrenia. The burden of schizophrenia exhibits distinct age-specific patterns in Asia, with the most pronounced peak occurring in middle adulthood, specifically between ages 35 and 39, as evidenced by global epidemiological data[ 23 ]. This elevated burden surpass that observed in other age groups, reflects the chronic and debilitating nature of schizophrenia, which manifests most acutely during this life stage. Following the typical onset in late adolescence or early adulthood[ 35 ], individuals in this age range have often endured a decade of illness, marked by cumulative disability and recurrent exacerbations [ 36 ]. Unlike younger individuals, who may benefit from early intervention, or older adults, who face fewer societal expectations, those aged 35–39 encounter heightened barriers to social and occupational reintegration due to persistent negative symptoms and cognitive deficits[ 37 , 38 ]. This period coincides with peak and competing work and family responsibilities[ 39 ], amplifying functional impairment. The interplay of prolonged illness and societal pressures drives the elevated burden in this age group. Regional patterns and disparities in schizophrenia burden Countries such as Vietnam, China, and the Maldives rank among those with the highest YLD rates attributable to schizophrenia, reflecting both elevated prevalence of the disorder and its profound cumulative impact in these populations. Rapid urbanization, economic shits, and population growth in these nations have likely intensified risk factors, including social isolation and environmental stress, which disproportionately exacerbate the burden of schizophrenia. In Vietnam and China, sprawling urban centers have disrupted traditional social networks, while in the Maldives, geographic dispersion across islands may heighten isolation, amplifying mental health challenges[ 40 , 41 ]. Moreover, limited investment in mental health infrastructure and lacks qualified primary care workers in these low-income and middle-income countries compound these issues[ 42 , 43 ], restricting access to early diagnosis and evidence-based treatment. In China, for instance, schizophrenia in urban locales more likely receive adequate mental health services compared to their rural counterparts due to resource disparities[ 44 ], while Vietnam and the Maldives face similar constraints stemming from underdeveloped psychiatric services[ 45 , 46 ]. Distinct patterns in YLD trends due to schizophrenia emerge between countries like Myanmar, where an increase is observed, and North Korea, where a decline is noted. In Myanmar, the rising trend may be attributed to enhanced data collection and elevated diagnosis rates by growing mental health awareness, alongside deteriorating social determinants of health, such as poverty and social disruption, exacerbated by ongoing armed conflicts and political unrest[ 47 ]. Conversely, declining YLD trend in North Korea likely reflects underreporting rather than a genuine reduction in disease burden, potentially due to inadequate mental health infrastructure and constraints on data reliability stemming from limited transparency and healthcare access[ 48 ]. The SDI illuminates the complex relationship between schizophrenia burden and societal development. Higher SDI regions, such as Japan, advanced healthcare infrastructure and accessible psychiatric services enable early diagnosis and management[ 49 , 50 ], paradoxically elevating YLDs rate. In contrast, low-SDI regions like Afghanistan reported lower YLDs, likely due to limited mental health resources, pervasive stigma, and underreporting rather than a lighter burden[ 51 , 52 ]. Yet, exceptions such as Bhutan, Pakistan, and Bangladesh, lower SDI countries with unexpectedly high YLD rates, highlighting the additional influences, including psychosocial, cultural, and political stressors[ 53 ]. These disparities underscore the intricate interplay of systemic, cultural, and environmental factors shaping the global burden of schizophrenia. Future projections in in schizophrenia burden The schizophrenia burden in Asia, particularly in rapidly developing nations such as China, India, and Indonesia, is forecasted to rise over the next three decades, driven by unique demographic and environmental dynamics. Population growth and aging would increase the absolute number of individuals with schizophrenia, as these countries host vast youth populations where onset typically peaks and carry the chronic effects of the disorder into later in life[ 54 ]. Rapid urbanization, a hallmark of development of these nations, heightens potential risk factors by overcrowding, social disconnection, and socio-economic disparities, all of which elevate schizophrenia incidence[ 55 ]. In China, for instance, urban migration often leads to social exclusion and poor mental health[ 56 , 57 ], while mental health services of India suffer from poor implementation, leaving a substantial treatment gap [ 58 ]. Similarly, Indonesia struggles with limited access to mental health service information[ 59 ]. These risks are compounded by entrenched socio-economic inequalities and persistent mental health infrastructure deficits, intensifying the projected burden. Despite economic advancements, mental health services in Asia, especially in developing countries, remain underfunded and unevenly distributed, with rural areas and low-income urban areas suffering from limited access to mental health services and human resource[ 60 , 61 ]. Cultural stigma, deeply rooted in societal attitudes, delayed help-seeking and poor adherence to treatment[ 62 , 63 ]. As substantial youthful demographic encounters these stressors and barriers[ 64 ], untreated cases will accumulate, driving a significant increase in schizophrenia-related disability over the coming decades. Implications and public health perspectives The escalating schizophrenia burden in high-growth Asian countries demands urgent public health action to prioritize mental health, particularly in high-burden and low-SDI regions. Policymakers should strengthen infrastructure through promoting early detection, accessible treatment, and rehabilitation, integrating mental healthcare into primary systems, and utilizing digital tools and community outreach[ 65 ]. Expanding psychiatric training, ensuring medication access, and addressing gender and age disparities, is critical to manage projected burden increases over the next 30 years. In low-SDI areas, mitigating inequities requires affordable care via effective funding and economic incentives, integrate into general healthcare systems, culturally tailored education campaigns to combat stigma[ 66 ]. Regional variations underscore the need for geographically specific strategies beyond economic growth. Collaboration among governments, NGOs, and communities is essential to bridge systemic gaps and improve outcomes. 5. Conclusion This study investigated the trends and burden of schizophrenia in Asia using GBD data 2021. Our findings indicate a consistent rise in the burden of schizophrenia from 1990 to 2021, with projections suggesting continued increases over the next three decades. Additionally, we identified a correlation between disease burden and the SDI across Asian countries and territories. These results highlight the urgent need for targeted interventions, including gender- and age-specific strategies, alongside equitable resource allocation to address pronounced disparities in low-income regions, aiming to mitigate the escalating burden of schizophrenia in Asia. Declarations Competing interests The authors declare no competing interests. Funding This study was funded by the Shaanxi Provincial Natural Science Basic Research Program (No.2024JC-YBQN-0209) and Clinical Medicine and X Research Center Project (No. LHJJ24XL03). Author Contribution Yuanjun Xie and Tian Zhang conceptualized and designed the study. Yuanjun Xie, Tian Zhang, and Naiting He drafted the initial manuscript. Junxin Zhou, Guangcai Chen, and Feixiang Hou analyzed the data and performed the statistical analyses. Yijun Li performed the visualization. Peng Fang, Chaozong Ma, and Chenxi Li critically revised the manuscript. All authors reviewed the drafted manuscript for critical content and approved the final version. Data availability statement The data analyzed in this study are available in the Global Health Data Exchange query tool ( https://vizhub.healthdata.org/gbd-results/ ). References Gogtay N, Vyas NS, Testa R, Wood SJ, Pantelis C (2011) Age of onset of schizophrenia: Perspectives from structural neuroimaging studies. Schizophr Bull 37(3):504–513 Insel TR (2010) Rethinking schizophrenia. Nature 468(7321):187–193 Carbon M, Correll CU (2014) Thinking and acting beyond the positive: the role of the cognitive and negative symptoms in schizophrenia. CNS Spectr 19(S1):35–53 Dong M, Lu L, Zhang L, Zhang Y-S, Ng CH, Ungvari GS, Li G, Meng X, Wang G, Xiang Y-T (2019) Quality of life in schizophrenia: A meta-analysis of comparative studies. Psychiatr Q 90(3):519–532 Zaprutko T, Kus K, Bilobryvka R, Rakhman L, Göder R, Michalak M, Pogłodziński A, Nowakowska E (2015) Schizophrenia and employment: Evaluation from professionals point of view. Psychiatr Q 86(4):569–579 Burns T, Patrick D (2007) Social functioning as an outcome measure in schizophrenia studies. Acta psychiatrica Scandinavica 116(6):403–418 Hjorthøj C, Stürup AE, McGrath JJ, Nordentoft M (2017) Years of potential life lost and life expectancy in schizophrenia: A systematic review and meta-analysis. Lancet Psychiatry 4(4):295–301 Liu NH, Daumit GL, Dua T, Aquila R, Charlson F, Cuijpers P, Druss B, Dudek K, Freeman M, Fujii C et al (2017) Excess mortality in persons with severe mental disorders: A multilevel intervention framework and priorities for clinical practice, policy and research agendas. World Psychiatry 16(1):30–40 Schoepf D, Uppal H, Potluri R, Heun R (2014) Physical comorbidity and its relevance on mortality in schizophrenia: a naturalistic 12-year follow-up in general hospital admissions. Eur Arch Psychiatry Clin NeuroSci 264(1):3–28 Charlson FJ, Baxter AJ, Dua T, Degenhardt L, Whiteford HA, Vos T (2015) Excess mortality from mental, neurological and substance use disorders in the Global Burden of Disease Study 2010. Epidemiol Psychiatric Sci 24(2):121–140 Häfner H, an der Heiden W (1997) Epidemiology of Schizophrenia. Can J Psychiatry 42(2):139–151 Charlson FJ, Ferrari AJ, Santomauro DF, Diminic S, Stockings E, Scott JG, McGrath JJ, Whiteford HA (2018) Global epidemiology and burden of schizophrenia: Findings from the global burden of disease study 2016. Schizophr Bull 44(6):1195–1203 Murray CJ, Lopez AD, Jamison DT (1994) The global burden of disease in 1990: summary results, sensitivity analysis and future directions. Bull World Health Organ 72(3):495–509 Murray CJL (2024) Findings from the Global Burden of Disease Study 2021. Lancet 403(10440):2259–2262 He H, Liu Q, Li N, Guo L, Gao F, Bai L, Gao F, Lyu J (2020) Trends in the incidence and DALYs of schizophrenia at the global, regional and national levels: results from the Global Burden of Disease Study 2017. Epidemiol Psychiatric Sci 29(1):e91 Solmi M, Seitidis G, Mavridis D, Correll CU, Dragioti E, Guimond S, Tuominen L, Dargél A, Carvalho AF, Fornaro M et al (2023) Incidence, prevalence, and global burden of schizophrenia - data, with critical appraisal, from the Global Burden of Disease (GBD) 2019. Mol Psychiatry 28(12):5319–5327 Murray CJL, Abbafati C, Abbas KM, Abbasi M, Abbasi-Kangevari M, Abd-Allah F, Abdollahi M, Abedi P, Abedi A, Abolhassani H et al (2020) Five insights from the global burden of disease study 2019. Lancet 396(10258):1135–1159 Vos T, Lim SS, Abbafati C, Abbas KM, Abbasi M, Abbasifard M, Abbasi-Kangevari M, Abbastabar H, Abd-Allah F, Abdelalim A et al (2020) Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet 396(10258):1204–1222 Stevens GA, Alkema L, Black RE, Boerma JT, Collins GS, Ezzati M, Grove JT, Hogan DR, Hogan MC, Horton R et al (2016) Guidelines for accurate and transparent health estimates reporting: The GATHER statement. Lancet 388(10062):e19–e23 Wang H, Abbas KM, Abbasifard M, Abbasi-Kangevari M, Abbastabar H, Abd-Allah F, Abdelalim A, Abolhassani H, Abreu LG, Abrigo MRM et al (2020) Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950–2019: A comprehensive demographic analysis for the Global Burden of Disease Study 2019. Lancet 396(10258):1160–1203 Clegg LX, Hankey BF, Tiwari R, Feuer EJ, Edwards BK (2009) Estimating average annual per cent change in trend analysis. Stat Med 28(29):3670–3682 Knoll M, Furkel J, Debus J, Abdollahi A, Karch A, Stock C (2020) An R package for an integrated evaluation of statistical approaches to cancer incidence projection. BMC Med Res Methodol 20(1):257 Ferrari AJ, Santomauro DF, Herrera AMM, Shadid J, Ashbaugh C, Erskine HE, Charlson FJ, Degenhardt L, Scott JG, McGrath JJ et al (2022) Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Psychiatry 9(2):137–150 Lederbogen F, Haddad L, Meyer-Lindenberg A (2013) Urban social stress – Risk factor for mental disorders. The case of schizophrenia. Environ Pollut 183(12):2–6 Krabbendam L, van Os J (2005) Schizophrenia and urbanicity: A major environmental influence—Conditional on genetic risk. Schizophr Bull 31(4):795–799 Chang AY, Skirbekk VF, Tyrovolas S, Kassebaum NJ, Dieleman JL (2019) Measuring population ageing: an analysis of the Global Burden of Disease Study 2017. Lancet Public Health 4(3):e159–e167 Xi J-Y, Lin X, Hao Y-T (2022) Measurement and projection of the burden of disease attributable to population aging in 188 countries, 1990–2050: A population-based study. J global health 12(10):04093 Cheng Y, Fang Y, Zheng J, Guan S, Wang M, Hong W (2024) The burden of depression, anxiety and schizophrenia among the older population in ageing and aged countries: An analysis of the Global Burden of Disease Study 2019. Gen Psychiatry 37(1):e101078 Uddin I, Khan MA, Tariq M, Khan F, Malik ZK (2024) Revisiting the determinants of life expectancy in Asia—exploring the role of institutional quality, financial development, and environmental degradation. Environ Dev Sustain 26(5):11289–11309 Xin L, Wanyan Z, Zhenghui Y (2022) A glimpse of gender differences in schizophrenia. Gen Psychiatry 35(4):e100823 Fernando P, Sommer IEC, Hasan A (2020) Do we need sex-oriented clinical practice guidelines for the treatment of schizophrenia? Curr Opin Psychiatry 33(3):192–199 Li R, Ma X, Wang G, Yang J, Wang C (2016) Why sex differences in schizophrenia? J Transl Neurosci (Beijing) 1(1):37–42 Grigoriadis S, Seeman MV (2002) The role of estrogen in schizophrenia: Implications for schizophrenia practice guidelines for women. Can J Psychiatry 47(5):437–442 McKenzie SK, Oliffe JL, Black A, Collings S (2022) Men’s experiences of mental illness stigma across the lifespan: A scoping review. Am J Men's Health 16(1):1–16 Gureje O (1991) Gender and schizophrenia: age at onset and sociodemographic attributes. Acta psychiatrica Scandinavica 83(5):402–405 Strassnig M, Signorile J, Gonzalez C, Harvey PD (2014) Physical performance and disability in schizophrenia. Schizophrenia Research: Cognition 1(2):112–121 O'Donnell BF (2007) Cognitive impairment in schizophrenia: A life span perspective. Am J Alzheimer's Dis Other dement 22(5):398–405 Millan M, Fone K, Steckler T (2014) Negative symptoms of schizophrenia: Clinical characteristics, pathophysiological substrates, experimental models and prospects for improved treatment. Eur Neuropsychopharmacol 24:645–692 Mehta CM, Arnett JJ, Palmer CG, Nelson LJ (2020) Established adulthood: A new conception of ages 30 to 45. Am Psychol 75(4):431–444 Ta TMT, Zieger A, Schomerus G, Cao TD, Dettling M, Do XT, Mungee A, Diefenbacher A, Angermeyer MC, Hahn E (2016) Influence of urbanity on perception of mental illness stigma: A population based study in urban and rural Hanoi, Vietnam. Int J Soc Psychiatry 62(8):685–695 Chan KY, Zhao F-f, Meng S, Demaio AR, Reed C, Theodoratou E, Campbell H, Wang W, Rudan I (2015) Urbanization and the prevalence of schizophrenia in China between 1990 and 2010. World Psychiatry 14(2):251–252 Saraceno B, van Ommeren M, Batniji R, Cohen A, Gureje O, Mahoney J, Sridhar D, Underhill C (2007) Barriers to improvement of mental health services in low-income and middle-income countries. Lancet 370(9593):1164–1174 Yang LH, Phillips MR, Li X, Yu G, Grivel MM, Zhang J, Shi Q, Ding Z, Pang S, Susser E (2022) Determinants of never-treated status in rural versus urban contexts for individuals with schizophrenia in a population-based study in China. BMC Psychiatry 22(1):128 Hou C-L, Chen M-Y, Cai M-Y, Chen Z-L, Cai S-B, Xiao Y-N, Jia F-J (2018) Antipsychotic-free status in community-dwelling patients with schizophrenia in China: Comparisons within and between rural and urban areas. J Clin Psychiatry 79(3):17m11599 Van NHN, Thi Khanh Huyen N, Hue MT, Luong NT, Quoc Thanh P, Duc DM, Thi Thanh Mai V, Hong TT (2021) Perceived barriers to mental health services among the elderly in the rural of Vietnam: A cross sectional survey in 2019. Health Serv Insights 14(6):1–10 Mohamed A, Mansoor S (2024) Challenges and opportunities in the mental health landscape of the Maldives. Australasian Psychiatry 32(5):1–2 Saw H-W, Owens V, Morales SA, Rodriguez N, Kern C, Bach RL (2023) Population mental health in Burma after 2021 military coup: online non-probability survey. BJPsych Open 9(5):e156 Lee H, Robinson C, Kim J, McKee M, Cha J (2020) Health and healthcare in North Korea: A retrospective study among defectors. Confl Health 14(1):41 Nishi D, Ishikawa H, Kawakami N (2019) Prevalence of mental disorders and mental health service use in Japan. J Neuropsychiatry Clin Neurosci 73(8):458–465 Nishi D, Susukida R, Usuda K, Mojtabai R, Yamanouchi Y (2018) Trends in the prevalence of psychological distress and the use of mental health services from 2007 to 2016 in Japan. J Affect Disord 239(10):208–213 Kovess-Masfety V, Karam E, Keyes K, Sabawoon A, Sarwari BA (2022) Access to care for mental health problems in Afghanistan: A national challenge. Int J Health Policy Manage 11(8):1442–1450 Schwartz L, Lane H, Hassanpoor Z (2023) Overview and understanding of mental health and psychosocial support in Afghanistan. Int Health 15(5):601–607 Naveed S, Waqas A, Chaudhary AMD, Kumar S, Abbas N, Amin R, Jamil N, Saleem S (2020) Prevalence of common mental disorders in south asia: A systematic review and meta-regression analysis. Front Psychiatry 11(9):573150 Ogawa N, Mansor N, Lee S-H, Abrigo MRM, Aris T (2021) Population aging and the three demographic dividends in Asia. Asian Dev Rev 38(1):32–67 Vassos E, Pedersen CB, Murray RM, Collier DA, Lewis CM (2012) Meta-analysis of the association of urbanicity with schizophrenia. Schizophr Bull 38(6):1118–1123 Li J, Rose N (2017) Urban social exclusion and mental health of China's rural-urban migrants – A review and call for research. Health Place 48(11):20–30 Li L, Wang H-m, Ye X-j, Jiang M-m, Lou Q-y, Hesketh T (2007) The mental health status of Chinese rural–urban migrant workers. Soc Psychiatry Psychiatr Epidemiol 42(9):716–722 Sagar R, Pattanayak RD, Chandrasekaran R, Chaudhury PK, Deswal BS, Lenin Singh RK, Malhotra S, Nizamie SH, Panchal BN, Sudhakar TP et al (2017) Twelve-month prevalence and treatment gap for common mental disorders: Findings from a large-scale epidemiological survey in India. Indian J Psychiatry 59(1):46–55 Putri AK, Gustriawanto N, Rahapsari S, Sholikhah AR, Prabaswara S, Kusumawardhani AC, Kristina SA (2021) Exploring the perceived challenges and support needs of Indonesian mental health stakeholders: A qualitative study. Int J Mental Health Syst 15(1):81 Maramis A, Van Tuan N, Minas H (2011) Mental health in southeast Asia. Lancet 377(9767):700–702 Maddock A, Blair C, Ean N, Best P (2021) Psychological and social interventions for mental health issues and disorders in Southeast Asia: a systematic review. Int J Mental Health Syst 15(1):56 Zhang Z, Sun K, Jatchavala C, Koh J, Chia Y, Bose J, Li Z, Tan W, Wang S, Chu W et al (2020) Overview of Stigma against Psychiatric Illnesses and Advancements of Anti-Stigma Activities in Six Asian Societies. Int J Environ Res Public Health vol 17:280 Vaishnav M, Javed A, Gupta S, Kumar V, Vaishnav P, Kumar A, Salih H, Levounis P, Ng B, Alkhoori S et al (2023) Stigma towards mental illness in Asian nations and low-and-middle-income countries, and comparison with high-income countries: A literature review and practice implications. Indian J Psychiatry 65(10):995–1011 Wittevrongel E, Kessels R, Everaert G, Vrijens M, Danckaerts M, van Winkel R (2025) A user perspective on youth mental health services: Increasing help-seeking behaviour requires addressing service preferences and attitudinal barriers. Early Interv Psychiat 19(1):e13584 Brian RM, Ben-Zeev D (2014) Mobile health (mHealth) for mental health in Asia: Objectives, strategies, and limitations. Asian J Psychiatry 10:96–100 Ito H, Setoya Y, Suzuki Y (2012) Lessons learned in developing community mental health care in East and South East Asia. World Psychiatry 11(3):186–190 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-6476890","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":453015267,"identity":"366d20fa-c972-4260-8990-5e34d0b9298d","order_by":0,"name":"Yuanjun Xie","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1klEQVRIiWNgGAWjYDACZijFDyITCkjRItkA0mJAim0GB8AkMSqPMx+T5qm5w258fnXihwcGDPL8Ygfwa5FsZkuT5jn2jNnsxtvNEkCHGc6cnYBfCz8zj5k0D9thoJazG0BaEgxuE9DCxsz/TZrn32Fm4xlnN/8gSgvQFjZp3rbDzAb8vduIswXoF2PLuX2HmSVu8G6zSDCQIOwXg/OHH9548+1wMn//2c03f1TYyPNLE9ACBCwSQCKZQQKsUoKgchBg/gAk7Bj4DxClehSMglEwCkYgAAB+Uj4kvbFfhAAAAABJRU5ErkJggg==","orcid":"","institution":"Sichuan University of Science and Engineering","correspondingAuthor":true,"prefix":"","firstName":"Yuanjun","middleName":"","lastName":"Xie","suffix":""},{"id":453015270,"identity":"da5d3cc8-ef6b-4a42-829e-6922fbccb84f","order_by":1,"name":"Tian Zhang","email":"","orcid":"","institution":"Air Force Medical University","correspondingAuthor":false,"prefix":"","firstName":"Tian","middleName":"","lastName":"Zhang","suffix":""},{"id":453015271,"identity":"b20ebd8f-23c5-46d7-8b7c-e602a5c901b1","order_by":2,"name":"Naiting He","email":"","orcid":"","institution":"Mental Health Center of Guangyuan","correspondingAuthor":false,"prefix":"","firstName":"Naiting","middleName":"","lastName":"He","suffix":""},{"id":453015272,"identity":"6587a6bf-ab11-4b7e-82f4-3dd2b673c914","order_by":3,"name":"Junxin Zhou","email":"","orcid":"","institution":"Mental Health Center of Guangyuan","correspondingAuthor":false,"prefix":"","firstName":"Junxin","middleName":"","lastName":"Zhou","suffix":""},{"id":453015273,"identity":"4e828e5e-24d1-4ce1-a7ab-38de222c5429","order_by":4,"name":"Guangcai Chen","email":"","orcid":"","institution":"Mental Health Center of Guangyuan","correspondingAuthor":false,"prefix":"","firstName":"Guangcai","middleName":"","lastName":"Chen","suffix":""},{"id":453015274,"identity":"eb4fb22d-020f-4999-a7ba-b0e5b9668b2e","order_by":5,"name":"Feixiang Hou","email":"","orcid":"","institution":"Mental Health Center of Guangyuan","correspondingAuthor":false,"prefix":"","firstName":"Feixiang","middleName":"","lastName":"Hou","suffix":""},{"id":453015275,"identity":"9181fe83-3418-4270-adc3-b29ba7aad39e","order_by":6,"name":"Yijun Li","email":"","orcid":"","institution":"Air Force Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yijun","middleName":"","lastName":"Li","suffix":""},{"id":453015276,"identity":"00340f74-3eba-4b87-851d-0dc65ce0a175","order_by":7,"name":"Peng Fang","email":"","orcid":"","institution":"Air Force Medical University","correspondingAuthor":false,"prefix":"","firstName":"Peng","middleName":"","lastName":"Fang","suffix":""},{"id":453015277,"identity":"831ee78f-fdef-4068-a5c9-f5a5dfa847cd","order_by":8,"name":"Chaozong Ma","email":"","orcid":"","institution":"Air Force Medical University","correspondingAuthor":false,"prefix":"","firstName":"Chaozong","middleName":"","lastName":"Ma","suffix":""},{"id":453015278,"identity":"4a490cad-dfcc-431b-bf69-42fa49433e59","order_by":9,"name":"Chenxi Li","email":"","orcid":"","institution":"Air Force Medical University","correspondingAuthor":false,"prefix":"","firstName":"Chenxi","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2025-04-18 07:23:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6476890/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6476890/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82580326,"identity":"8ab13db7-08c3-4101-ae8d-e18a759df2df","added_by":"auto","created_at":"2025-05-13 06:31:26","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":210692,"visible":true,"origin":"","legend":"\u003cp\u003eTemporal trend of global prevalence, incidence, YLDs cases, and rate of schizophrenia in all ages. The shading represents the 95% uncertainty interval.\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-6476890/v1/346712300ca2715d746cf460.png"},{"id":82580327,"identity":"b1baafa0-8770-4a50-95a3-fbb296079718","added_by":"auto","created_at":"2025-05-13 06:31:26","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":343516,"visible":true,"origin":"","legend":"\u003cp\u003eAge and sex-specific age-standardized YLDs rate of schizophrenia in 2021. Bars represent number of cases and lines represent age-specific rates. YLDs, years of life disability.\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-6476890/v1/bf57305e79de840fbd95b7c1.png"},{"id":82581829,"identity":"afba8626-6d0d-40b6-999e-14a7c663d54f","added_by":"auto","created_at":"2025-05-13 06:39:26","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":238086,"visible":true,"origin":"","legend":"\u003cp\u003eAge-standardized YLDs rate of schizophrenia in Asian countries and territories, between 1990 (a) and 2021 (b), and the EPAC from 1990 to 2021 (c).\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-6476890/v1/b93fc808987d9a3b0cda523d.png"},{"id":82580333,"identity":"458006e6-7480-4b6d-8387-c5f9bf6b9728","added_by":"auto","created_at":"2025-05-13 06:31:26","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":150482,"visible":true,"origin":"","legend":"\u003cp\u003eThe correlation between the age-standardized YLDs and SDI from 1990 to 2021.\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-6476890/v1/58293e3a37f75cfa1f733e76.png"},{"id":82580328,"identity":"33ebda0e-7769-4ac7-a63d-0bcd463e562f","added_by":"auto","created_at":"2025-05-13 06:31:26","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":185087,"visible":true,"origin":"","legend":"\u003cp\u003eThe prediction of YLDs rates in Asia (a), China (b), India, and Indonesia (d) of schizophrenia from 1990 to 2053.\u003c/p\u003e","description":"","filename":"image5.png","url":"https://assets-eu.researchsquare.com/files/rs-6476890/v1/cdbd2a6ac6a46f75b2766963.png"},{"id":94474116,"identity":"a7d0cc3c-6543-495e-9788-1d1aefed2742","added_by":"auto","created_at":"2025-10-27 15:47:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1842385,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6476890/v1/fece5290-c771-4547-a550-6974768cad04.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Trends and burden of schizophrenia in Asia: Insights from the global burden of disease study 2021","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eSchizophrenia is a severe and life-long mental health disorder, typically emerges in late adolescence and early adulthood [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], affects roughly one percent of the population [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. This disease is usually characterized by three categories of symptoms, including positive symptoms (e.g., hallucinations and delusion), negative symptoms (e.g., apathy and avolition ), and cognitive impairments (e.g., problems with memory and attention) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Although it affects a minority of the global population, it profound impact on quality of life [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], and induces extensive social functioning and employment problems [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSchizophrenia is associated with a significantly reduced life expectancy, averaging approximately 14.5 years shorter than the general population, with men experiencing a greater reduction than women [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In addition to an unhealthy lifestyle exacerbated by low income and limited access to healthcare [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], physical comorbidity and increased inflammation may also contribute to the observed decrease in life expectancy [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Unnatural causes, such as suicide, contribute to less than 15% of the excess deaths [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The peak prevalence and disability burden are observed around the age of 35 years in both sexes [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Additionally, the disease is disproportionately higher in low- and middle-income countries, reaching up to four times that observed in high-income regions [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite the significant burden of schizophrenia, public health efforts remain constrained by insufficient data on the geographic and temporal variations of the disease. Understanding the epidemiological trends of schizophrenia is critical for optimizing resource allocation and developing targeted interventions to mitigate its impact. The Global Burden of Disease (GBD) study provides a comprehensive framework for analyzing the prevalence, incidence, and burden of medical disorders, including mental disorders and schizophrenia across diverse regions and demographic groups. First quantified in 1990 by the World Health Organization in 1990 [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], the GBD study has since evolved significantly. The most recent iterations, GBD 2021, carried out by the Institute for Health Metrics and Evaluation (IHME) at the University of Washington[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], incorporates notable methodological advancements.\u003c/p\u003e \u003cp\u003ePrevious studies have reported on the GBD estimates of schizophrenia, highlighting its global prevalence, incidence, or burden [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. For instance, 2016 GBD data revealed that the raw prevalence of schizophrenia increased from over 13\u0026nbsp;million cases in 1990 to nearly 21\u0026nbsp;million cases by 2016 [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], and this disorder accounted for approximately 13\u0026nbsp;million years of life lived with disability, underscoring its significant contribution to the global burden of disease. However, there is a notable lack of comprehensive, detailed findings specifically addressing the burden of schizophrenia in Asia. This study aimed to address this gap by reporting on the epidemiological trends and disease burden of schizophrenia in Asian countries and territories between 1990 to 2021 based on GBD 2021 data. Furthermore, the analyses of the association between schizophrenia burden and the sociodemographic index (SDI) as well as predictions regarding this disease burden were performed to provide insights into patters of schizophrenia burden across different regions.\u003c/p\u003e"},{"header":"2. Matherials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Data source\u003c/h2\u003e \u003cp\u003eThe data utilized in this study is available on GBD database (1990\u0026ndash;2021) (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://ghdx.healthdata.org\u003c/span\u003e\u003cspan address=\"http://ghdx.healthdata.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). GBD is an international collaborative initiative dedicated to providing a comprehensive overview of the current state of diseases worldwide and is recognized as one of the most comprehensive and systematic global epidemiological efforts [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The GBD framework enables comparative assessments of prevalence, incidence, mortality, and YLDs estimates. The dataset comprises annual data for the world, Asia, and 49 Asian countries and territories. The prevalence, incidence, and YLDs estimates were extracted in cases and rates, stratified by region, countries, territory, age, and sex. Additionally, age-standardized YLDs rates were calculated using the GBD world population standard to ensure comparability across populations. All estimates are reported as numbers and rates per 100,000 population, accompanied by 95% uncertainty intervals (UI)[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Each step used in this study to analyze the GBD database was consistent with the Guidelines for Accurate and Transparent Health Estimates Reporting, which has been described in detail previously [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Case definition\u003c/h2\u003e \u003cp\u003eSchizophrenia is defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria (DSM-IV-TR: 295.10-295.30, 295.60, 295.90) or the International Classification of Diseases (ICD) criteria (ICD-10: F20), as detailed under the GBD classification code B.6.1. The diagnostic criteria included the following several key elements[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]:(1) the present of at least two of the following symptoms for a significant portion of a one-month period: delusion, hallucinations, disorganized speech, markedly disorganized or catatonic behavior, and negative symptoms; (2) significant dysfunction in social or occupational functioning;(3) the persistence of signs and symptoms for at least six months;(4) the exclusion of alternative causes, such as substance use, schizoaffective or mood disorders, general medical conditions, or a connection to pervasive developmental disorders.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Sociodemographic index\u003c/h2\u003e \u003cp\u003eThe burden of schizophrenia was evaluated in relation to national development levels, as measured by the socio-demographic Index (SDI)[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. The SDI is a composite indicator of development status as it pertains to health outcomes, ranges from 0 to 1, with higher values indicating higher socioeconomic development. For Asian countries and territories, SDI values were categorized into five distinct quintiles: low SDI (\u0026lt;\u0026thinsp;0.45), low-middle SDI (\u0026ge;\u0026thinsp;0.45 and \u0026lt;\u0026thinsp;0.61), middle SDI (\u0026ge;\u0026thinsp;0.61 and \u0026lt;\u0026thinsp;0.69), high-middle SDI (\u0026ge;\u0026thinsp;0.69 and \u0026lt;\u0026thinsp;0.80), and high SDI (\u0026ge;\u0026thinsp;0.80).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Statistical analysis\u003c/h2\u003e \u003cp\u003ePrevalence, Incidence, and YLDs rates were calculated per 100,000 population according to the GBD database statistics. Trends in disease burden (YLDs) were assessed based on the average annual percentage change (EAPC). The calculation of EAPC and its confidence intervals (CI) were based on a log-transformed linear regression model during a specified period[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. An EAPC value and the lower limit of its 95% CI greater than 0 indicate an increasing trend for the corresponding indicator (e.g., YLDs). Conversely, an EAPC value and the upper limit of its 95% CI less than 0 indicate a decreasing trend for the corresponding indicator (e.g., YLDs).\u003c/p\u003e \u003cp\u003eThe Bayesian age-period-cohort (BAPC) model was applied to forecast the future change in the burden of schizophrenia in 2050. The BAPC model addresses the parameter estimation challenges arising from the linear relationship between age, period, and cohort by incorporating Bayesian priors and using the Integrated Nested Laplace Approximation (INLA) algorithm[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. All statistical analyses were performed using R (version 4.4.2; \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).\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.1. Global Trends\u003c/h2\u003e \u003cp\u003eIn Asia, there has been a consistent increase in prevalence, incidence, and YLDs due to schizophrenia from 1990 to 2021 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Specifically, the prevalence cases of schizophrenia showed a steady increase, rising from approximately 8.42\u0026nbsp;million (95%UI:9.91\u0026ndash;7.03) in 1990 to nearly 14.96\u0026nbsp;million (95%UI:12.56\u0026ndash;17.54) in 2021. Throughout this period, the prevalence was consistently higher in males compared to females. The number of prevalent cases among males rose from approximately 4.60\u0026nbsp;million (95%UI:3.83\u0026ndash;5.43) in 1990 to around 8.11\u0026nbsp;million (6.80\u0026ndash;9.54) in 2021, with an increase of 76.30%; while females saw an increase from 3.82\u0026nbsp;million (95%UI: 3.19\u0026ndash;4.50) to approximately 6.85\u0026nbsp;million (95%UI:5.75\u0026ndash;8.01) over the same period, with an increase of 79.32%.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eSimilarly, in 2021, there were 0.77\u0026nbsp;million incidence cases of schizophrenia reported in Asian, reflecting a 32.76% increase since 1990. The incidence among males was consistently higher than among females, with 0.43\u0026nbsp;million cases (95UI:0.36\u0026ndash;0.52) reported in males and 0.34\u0026nbsp;million cases (95%UI:0.28\u0026ndash;0.41) in female. Notably, the increase in incidence was greater for males compared to female, with growth rates of 34.38% and 30.77%, respectively, between 1990 to 2021.\u003c/p\u003e \u003cp\u003eIn addition, in 2021, schizophrenia accounted for 5.45\u0026nbsp;million YLDs in Asia. Males contributed a larger portion of these YLDs, representing approximately 55.23% of the total. The YLD rate per 100,000 people for schizophrenia in Asia showed an increasing trend, rising from 171.70 (95% UI: 127.83\u0026ndash;219.6) in 1990 to 208.07 (95% UI: 154.45-266.72) in 2021.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eprevalence, incidence, and YLDs in schizophrenia from 1990 to 2021\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003ePrevalence (million,95%UI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eIncidence (million,95%UI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eYLDs (million,95%UI)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1990\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1990\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1990\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBoth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.42(9.91\u0026ndash;7.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.96(12.56\u0026ndash;17.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.58(0.47\u0026ndash;0.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.77(0.64\u0026ndash;0.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.45(4.59\u0026ndash;6.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9.62(7.14\u0026ndash;12.33)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.60(3.83\u0026ndash;5.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.11(6.80\u0026ndash;9.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.32(0.26\u0026ndash;0.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.43(0.36\u0026ndash;0.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.01(2.23\u0026ndash;3.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.28(3.92\u0026ndash;6.77)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.82(3.19\u0026ndash;4.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.85(5.75\u0026ndash;8.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.26(0.21\u0026ndash;0.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.34(0.28\u0026ndash;0.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.44(1.83\u0026ndash;3.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.34(3.22\u0026ndash;5.55)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Age and sex effects\u003c/h2\u003e \u003cp\u003eThe age and sex-specific burden of schizophrenia in Asia, as depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, revealed distinct age-related variation. The age-standardized YLDs rate progressively increased from early adolescence, reaching its peak in the 35\u0026ndash;39 years age group (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea). In addition, the rate was generally higher in males than in females across most age ranges (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb), except for the oldest age groups, such as those aged above 85 years.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Disease burden by country\u003c/h2\u003e \u003cp\u003eIn 1990, the countries and territories with the highest age-standardized YLDs rate (per 100,000) for schizophrenia in Asia were predominantly located in East and Southeast (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea). Vietnam reported the highest rate at 1991.16 (95%UI:138.30-270.05), followed by China at 195.67 (95%UI:147.78-244.07), Taiwan at 135.34 (95%UI:135.34-257.68), and Malaysia at 189.04 (95%UI:133.04-266.36). By 2021, the burden of schizophrenia remained significant (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eb), with Vietnam still having the highest age-standardized YLDs rate (209.00; 95%UI:148.09-283.33), followed by China (203.88; 95%UI:152.53-255.67), Taiwan (202.09; 95%UI:143.27-277.15), and the Maldives (200.74; 95%UI:143.69-272.62).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOver the three decades, the EAPC analysis revealed heterogeneous trends in the schizophrenia burden across Asia (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec). Myanmar (+\u0026thinsp;0.31; 95%CI:0.27\u0026ndash;0.36), Maldives (+\u0026thinsp;0.27; 95%CI:0.22\u0026ndash;0.31), and Laos (+\u0026thinsp;0.26; 95%CI:0.22\u0026ndash;0.29) exhibited the most notable increase in the burden of schizophrenia. In contrast, North Korea (-0.16; 95%CI: -0.17 to -0.14), the United Arab Emirates (-0.12; 95%CI: -0.13 to -0.11), and Pakistan (-0.08; 95%CI:-0.09 to -0.07) exhibited the largest declines.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Relationship between disease burden and SDI levels\u003c/h2\u003e \u003cp\u003eThe relationship between age-standardized YLDs rates and SDI level for each country was presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e5\u003c/span\u003e. It turned out that there was a significant association between burden estimates of schizophrenia and SDI levels for each country in Asia during the observation period.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eRegions with higher SDI levels tend to have higher age-standardized YLDs rates for schizophrenia. For example, high-SDI regions like Japan exhibit some of the highest YLD rates, while low-SDI regions, such as Afghanistan, show consistently lower rates. However, the variation within SDI levels is notable, as certain regions like Bhutan, Pakistan, and India deviate from the general trend, displaying relatively high YLD rates despite lower SDI rankings.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.5 Prediction of disease burden\u003c/h2\u003e \u003cp\u003eAs illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e4\u003c/span\u003e, the YLDs rates among the Asia and the selected largest population countries, namely China, India, and Indonesia remained relative stable, and slowly increasing trend historically. The overall trend of increasing YLDs rate in Asia and these selected countries are predicted to continue for the further 30 years.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThe present study investigated the trend and burden of schizophrenia in Asia using GBD data 2021. The findings revealed the growing burden of schizophrenia, with increases in prevalence, incidence, and YLDs. Prevalence rose from 8.42\u0026nbsp;million cases in 1990 to 14.96\u0026nbsp;million in 2021, with males consistently exhibiting higher rates. Incidence grew by 32.76%, also with greater increases in males. In 2021, schizophrenia caused 5.45\u0026nbsp;million YLDs, peaking in middle adulthood (35\u0026ndash;39 years) and higher in males. Vietnam had the highest age-standardized YLD rates, followed by China, Taiwan, and the Maldives. Over time, some countries like Myanmar and Maldives, experienced increases, while others, such as North Korea and Pakistan, saw declines. Higher SDI levels were linked to higher YLD rates, although exceptions were observed. Projections indicate continued increases in schizophrenia-related YLDs over the next three decades.\u003c/p\u003e \u003cp\u003e \u003cb\u003eKey trends in schizophrenia burden\u003c/b\u003e \u003c/p\u003e \u003cp\u003eOver the past three decades, the prevalence, incidence, and YLDs rate attributable to schizophrenia have shown a consistent upward trajectory[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], with Asia experiencing the most pronounced rise. This pattern underscores the growing public health challenge posed by this severe mental disorder, particularly in regions undergoing rapid demographic shifts and epidemiological transitions. Socioeconomic factors appear to play a critical role in driving these trends. Urbanization, for instance, has been associated with a heightened risk of schizophrenia, attributed to factors such as increased social stress, exposure to environmental pollutants, and the weakening of social support networks. These dynamics have contributed to the rising prevalence and incidence of the disorder[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Concurrently, demographic changes, such as population growth and aging, have further exacerbated the disease burden [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], particularly in Asia. As global life expectancy continues to increase alongside with financial development [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], greater healthcare budget allocation, the adoption of clean and sustainable technology [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], the protracted duration of chronic mental disorders like schizophrenia has further intensified the cumulative burden.\u003c/p\u003e \u003cp\u003eGlobally, the burden of schizophrenia remains disproportionately higher among males than females[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Males tend to exhibit a greater vulnerability to an earlier age of onset and severe symptomatology[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e], consistent with previous research attributing these disparities to confluence of genetic, neurodevelopmental, and hormonal influences[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. For instance, estrogen is postulated to play a neuroprotective role in mitigating schizophrenia pathology in women[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Additionally, in some societies, social factors such as the stigma associated with mental illness, may exacerbate this burden by limiting healthcare access among males[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], who are generally less likely to seek mental health treatment compared to females. These changes are further compounded by the complexity associated with aging populations [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], including gender-specific survival rates, patterns of comorbidities, and shifts in demographic structures, all of which influence observed trends in the burden of schizophrenia.\u003c/p\u003e \u003cp\u003eThe burden of schizophrenia exhibits distinct age-specific patterns in Asia, with the most pronounced peak occurring in middle adulthood, specifically between ages 35 and 39, as evidenced by global epidemiological data[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. This elevated burden surpass that observed in other age groups, reflects the chronic and debilitating nature of schizophrenia, which manifests most acutely during this life stage. Following the typical onset in late adolescence or early adulthood[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e], individuals in this age range have often endured a decade of illness, marked by cumulative disability and recurrent exacerbations [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Unlike younger individuals, who may benefit from early intervention, or older adults, who face fewer societal expectations, those aged 35\u0026ndash;39 encounter heightened barriers to social and occupational reintegration due to persistent negative symptoms and cognitive deficits[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. This period coincides with peak and competing work and family responsibilities[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e], amplifying functional impairment. The interplay of prolonged illness and societal pressures drives the elevated burden in this age group.\u003c/p\u003e \u003cp\u003e \u003cb\u003eRegional patterns and disparities in schizophrenia burden\u003c/b\u003e \u003c/p\u003e \u003cp\u003eCountries such as Vietnam, China, and the Maldives rank among those with the highest YLD rates attributable to schizophrenia, reflecting both elevated prevalence of the disorder and its profound cumulative impact in these populations. Rapid urbanization, economic shits, and population growth in these nations have likely intensified risk factors, including social isolation and environmental stress, which disproportionately exacerbate the burden of schizophrenia. In Vietnam and China, sprawling urban centers have disrupted traditional social networks, while in the Maldives, geographic dispersion across islands may heighten isolation, amplifying mental health challenges[\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. Moreover, limited investment in mental health infrastructure and lacks qualified primary care workers in these low-income and middle-income countries compound these issues[\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e], restricting access to early diagnosis and evidence-based treatment. In China, for instance, schizophrenia in urban locales more likely receive adequate mental health services compared to their rural counterparts due to resource disparities[\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e], while Vietnam and the Maldives face similar constraints stemming from underdeveloped psychiatric services[\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e, \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDistinct patterns in YLD trends due to schizophrenia emerge between countries like Myanmar, where an increase is observed, and North Korea, where a decline is noted. In Myanmar, the rising trend may be attributed to enhanced data collection and elevated diagnosis rates by growing mental health awareness, alongside deteriorating social determinants of health, such as poverty and social disruption, exacerbated by ongoing armed conflicts and political unrest[\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. Conversely, declining YLD trend in North Korea likely reflects underreporting rather than a genuine reduction in disease burden, potentially due to inadequate mental health infrastructure and constraints on data reliability stemming from limited transparency and healthcare access[\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe SDI illuminates the complex relationship between schizophrenia burden and societal development. Higher SDI regions, such as Japan, advanced healthcare infrastructure and accessible psychiatric services enable early diagnosis and management[\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e], paradoxically elevating YLDs rate. In contrast, low-SDI regions like Afghanistan reported lower YLDs, likely due to limited mental health resources, pervasive stigma, and underreporting rather than a lighter burden[\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e, \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. Yet, exceptions such as Bhutan, Pakistan, and Bangladesh, lower SDI countries with unexpectedly high YLD rates, highlighting the additional influences, including psychosocial, cultural, and political stressors[\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]. These disparities underscore the intricate interplay of systemic, cultural, and environmental factors shaping the global burden of schizophrenia.\u003c/p\u003e \u003cp\u003e \u003cb\u003eFuture projections in in schizophrenia burden\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe schizophrenia burden in Asia, particularly in rapidly developing nations such as China, India, and Indonesia, is forecasted to rise over the next three decades, driven by unique demographic and environmental dynamics. Population growth and aging would increase the absolute number of individuals with schizophrenia, as these countries host vast youth populations where onset typically peaks and carry the chronic effects of the disorder into later in life[\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]. Rapid urbanization, a hallmark of development of these nations, heightens potential risk factors by overcrowding, social disconnection, and socio-economic disparities, all of which elevate schizophrenia incidence[\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e]. In China, for instance, urban migration often leads to social exclusion and poor mental health[\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e, \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e], while mental health services of India suffer from poor implementation, leaving a substantial treatment gap [\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e]. Similarly, Indonesia struggles with limited access to mental health service information[\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThese risks are compounded by entrenched socio-economic inequalities and persistent mental health infrastructure deficits, intensifying the projected burden. Despite economic advancements, mental health services in Asia, especially in developing countries, remain underfunded and unevenly distributed, with rural areas and low-income urban areas suffering from limited access to mental health services and human resource[\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e, \u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e]. Cultural stigma, deeply rooted in societal attitudes, delayed help-seeking and poor adherence to treatment[\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e, \u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e]. As substantial youthful demographic encounters these stressors and barriers[\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e], untreated cases will accumulate, driving a significant increase in schizophrenia-related disability over the coming decades.\u003c/p\u003e \u003cp\u003e \u003cb\u003eImplications and public health perspectives\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe escalating schizophrenia burden in high-growth Asian countries demands urgent public health action to prioritize mental health, particularly in high-burden and low-SDI regions. Policymakers should strengthen infrastructure through promoting early detection, accessible treatment, and rehabilitation, integrating mental healthcare into primary systems, and utilizing digital tools and community outreach[\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e]. Expanding psychiatric training, ensuring medication access, and addressing gender and age disparities, is critical to manage projected burden increases over the next 30 years. In low-SDI areas, mitigating inequities requires affordable care via effective funding and economic incentives, integrate into general healthcare systems, culturally tailored education campaigns to combat stigma[\u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e]. Regional variations underscore the need for geographically specific strategies beyond economic growth. Collaboration among governments, NGOs, and communities is essential to bridge systemic gaps and improve outcomes.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eThis study investigated the trends and burden of schizophrenia in Asia using GBD data 2021. Our findings indicate a consistent rise in the burden of schizophrenia from 1990 to 2021, with projections suggesting continued increases over the next three decades. Additionally, we identified a correlation between disease burden and the SDI across Asian countries and territories. These results highlight the urgent need for targeted interventions, including gender- and age-specific strategies, alongside equitable resource allocation to address pronounced disparities in low-income regions, aiming to mitigate the escalating burden of schizophrenia in Asia.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e \u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis study was funded by the Shaanxi Provincial Natural Science Basic Research Program (No.2024JC-YBQN-0209) and Clinical Medicine and X Research Center Project (No. LHJJ24XL03).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eYuanjun Xie and Tian Zhang conceptualized and designed the study. Yuanjun Xie, Tian Zhang, and Naiting He drafted the initial manuscript. Junxin Zhou, Guangcai Chen, and Feixiang Hou analyzed the data and performed the statistical analyses. Yijun Li performed the visualization. Peng Fang, Chaozong Ma, and Chenxi Li critically revised the manuscript. All authors reviewed the drafted manuscript for critical content and approved the final version.\u003c/p\u003e\u003ch2\u003eData availability statement\u003c/h2\u003e \u003cp\u003eThe data analyzed in this study are available in the Global Health Data Exchange query 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).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGogtay N, Vyas NS, Testa R, Wood SJ, Pantelis C (2011) Age of onset of schizophrenia: Perspectives from structural neuroimaging studies. Schizophr Bull 37(3):504\u0026ndash;513\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eInsel TR (2010) Rethinking schizophrenia. Nature 468(7321):187\u0026ndash;193\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCarbon M, Correll CU (2014) Thinking and acting beyond the positive: the role of the cognitive and negative symptoms in schizophrenia. CNS Spectr 19(S1):35\u0026ndash;53\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDong M, Lu L, Zhang L, Zhang Y-S, Ng CH, Ungvari GS, Li G, Meng X, Wang G, Xiang Y-T (2019) Quality of life in schizophrenia: A meta-analysis of comparative studies. Psychiatr Q 90(3):519\u0026ndash;532\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZaprutko T, Kus K, Bilobryvka R, Rakhman L, G\u0026ouml;der R, Michalak M, Pogłodziński A, Nowakowska E (2015) Schizophrenia and employment: Evaluation from professionals point of view. Psychiatr Q 86(4):569\u0026ndash;579\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBurns T, Patrick D (2007) Social functioning as an outcome measure in schizophrenia studies. Acta psychiatrica Scandinavica 116(6):403\u0026ndash;418\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHjorth\u0026oslash;j C, St\u0026uuml;rup AE, McGrath JJ, Nordentoft M (2017) Years of potential life lost and life expectancy in schizophrenia: A systematic review and meta-analysis. Lancet Psychiatry 4(4):295\u0026ndash;301\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu NH, Daumit GL, Dua T, Aquila R, Charlson F, Cuijpers P, Druss B, Dudek K, Freeman M, Fujii C et al (2017) Excess mortality in persons with severe mental disorders: A multilevel intervention framework and priorities for clinical practice, policy and research agendas. World Psychiatry 16(1):30\u0026ndash;40\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchoepf D, Uppal H, Potluri R, Heun R (2014) Physical comorbidity and its relevance on mortality in schizophrenia: a naturalistic 12-year follow-up in general hospital admissions. Eur Arch Psychiatry Clin NeuroSci 264(1):3\u0026ndash;28\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCharlson FJ, Baxter AJ, Dua T, Degenhardt L, Whiteford HA, Vos T (2015) Excess mortality from mental, neurological and substance use disorders in the Global Burden of Disease Study 2010. Epidemiol Psychiatric Sci 24(2):121\u0026ndash;140\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eH\u0026auml;fner H, an der Heiden W (1997) Epidemiology of Schizophrenia. Can J Psychiatry 42(2):139\u0026ndash;151\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCharlson FJ, Ferrari AJ, Santomauro DF, Diminic S, Stockings E, Scott JG, McGrath JJ, Whiteford HA (2018) Global epidemiology and burden of schizophrenia: Findings from the global burden of disease study 2016. Schizophr Bull 44(6):1195\u0026ndash;1203\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMurray CJ, Lopez AD, Jamison DT (1994) The global burden of disease in 1990: summary results, sensitivity analysis and future directions. Bull World Health Organ 72(3):495\u0026ndash;509\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMurray CJL (2024) Findings from the Global Burden of Disease Study 2021. Lancet 403(10440):2259\u0026ndash;2262\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHe H, Liu Q, Li N, Guo L, Gao F, Bai L, Gao F, Lyu J (2020) Trends in the incidence and DALYs of schizophrenia at the global, regional and national levels: results from the Global Burden of Disease Study 2017. Epidemiol Psychiatric Sci 29(1):e91\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSolmi M, Seitidis G, Mavridis D, Correll CU, Dragioti E, Guimond S, Tuominen L, Darg\u0026eacute;l A, Carvalho AF, Fornaro M et al (2023) Incidence, prevalence, and global burden of schizophrenia - data, with critical appraisal, from the Global Burden of Disease (GBD) 2019. Mol Psychiatry 28(12):5319\u0026ndash;5327\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMurray CJL, Abbafati C, Abbas KM, Abbasi M, Abbasi-Kangevari M, Abd-Allah F, Abdollahi M, Abedi P, Abedi A, Abolhassani H et al (2020) Five insights from the global burden of disease study 2019. Lancet 396(10258):1135\u0026ndash;1159\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVos T, Lim SS, Abbafati C, Abbas KM, Abbasi M, Abbasifard M, Abbasi-Kangevari M, Abbastabar H, Abd-Allah F, Abdelalim A et al (2020) Global burden of 369 diseases and injuries in 204 countries and territories, 1990\u0026ndash;2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet 396(10258):1204\u0026ndash;1222\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStevens GA, Alkema L, Black RE, Boerma JT, Collins GS, Ezzati M, Grove JT, Hogan DR, Hogan MC, Horton R et al (2016) Guidelines for accurate and transparent health estimates reporting: The GATHER statement. Lancet 388(10062):e19\u0026ndash;e23\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang H, Abbas KM, Abbasifard M, Abbasi-Kangevari M, Abbastabar H, Abd-Allah F, Abdelalim A, Abolhassani H, Abreu LG, Abrigo MRM et al (2020) Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950\u0026ndash;2019: A comprehensive demographic analysis for the Global Burden of Disease Study 2019. Lancet 396(10258):1160\u0026ndash;1203\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eClegg LX, Hankey BF, Tiwari R, Feuer EJ, Edwards BK (2009) Estimating average annual per cent change in trend analysis. Stat Med 28(29):3670\u0026ndash;3682\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKnoll M, Furkel J, Debus J, Abdollahi A, Karch A, Stock C (2020) An R package for an integrated evaluation of statistical approaches to cancer incidence projection. BMC Med Res Methodol 20(1):257\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFerrari AJ, Santomauro DF, Herrera AMM, Shadid J, Ashbaugh C, Erskine HE, Charlson FJ, Degenhardt L, Scott JG, McGrath JJ et al (2022) Global, 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. Lancet Psychiatry 9(2):137\u0026ndash;150\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLederbogen F, Haddad L, Meyer-Lindenberg A (2013) Urban social stress \u0026ndash; Risk factor for mental disorders. The case of schizophrenia. Environ Pollut 183(12):2\u0026ndash;6\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKrabbendam L, van Os J (2005) Schizophrenia and urbanicity: A major environmental influence\u0026mdash;Conditional on genetic risk. Schizophr Bull 31(4):795\u0026ndash;799\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChang AY, Skirbekk VF, Tyrovolas S, Kassebaum NJ, Dieleman JL (2019) Measuring population ageing: an analysis of the Global Burden of Disease Study 2017. Lancet Public Health 4(3):e159\u0026ndash;e167\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXi J-Y, Lin X, Hao Y-T (2022) Measurement and projection of the burden of disease attributable to population aging in 188 countries, 1990\u0026ndash;2050: A population-based study. J global health 12(10):04093\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCheng Y, Fang Y, Zheng J, Guan S, Wang M, Hong W (2024) The burden of depression, anxiety and schizophrenia among the older population in ageing and aged countries: An analysis of the Global Burden of Disease Study 2019. Gen Psychiatry 37(1):e101078\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUddin I, Khan MA, Tariq M, Khan F, Malik ZK (2024) Revisiting the determinants of life expectancy in Asia\u0026mdash;exploring the role of institutional quality, financial development, and environmental degradation. Environ Dev Sustain 26(5):11289\u0026ndash;11309\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXin L, Wanyan Z, Zhenghui Y (2022) A glimpse of gender differences in schizophrenia. Gen Psychiatry 35(4):e100823\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFernando P, Sommer IEC, Hasan A (2020) Do we need sex-oriented clinical practice guidelines for the treatment of schizophrenia? Curr Opin Psychiatry 33(3):192\u0026ndash;199\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi R, Ma X, Wang G, Yang J, Wang C (2016) Why sex differences in schizophrenia? J Transl Neurosci (Beijing) 1(1):37\u0026ndash;42\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrigoriadis S, Seeman MV (2002) The role of estrogen in schizophrenia: Implications for schizophrenia practice guidelines for women. Can J Psychiatry 47(5):437\u0026ndash;442\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcKenzie SK, Oliffe JL, Black A, Collings S (2022) Men\u0026rsquo;s experiences of mental illness stigma across the lifespan: A scoping review. Am J Men's Health 16(1):1\u0026ndash;16\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGureje O (1991) Gender and schizophrenia: age at onset and sociodemographic attributes. Acta psychiatrica Scandinavica 83(5):402\u0026ndash;405\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStrassnig M, Signorile J, Gonzalez C, Harvey PD (2014) Physical performance and disability in schizophrenia. Schizophrenia Research: Cognition 1(2):112\u0026ndash;121\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eO'Donnell BF (2007) Cognitive impairment in schizophrenia: A life span perspective. Am J Alzheimer's Dis Other dement 22(5):398\u0026ndash;405\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMillan M, Fone K, Steckler T (2014) Negative symptoms of schizophrenia: Clinical characteristics, pathophysiological substrates, experimental models and prospects for improved treatment. Eur Neuropsychopharmacol 24:645\u0026ndash;692\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMehta CM, Arnett JJ, Palmer CG, Nelson LJ (2020) Established adulthood: A new conception of ages 30 to 45. Am Psychol 75(4):431\u0026ndash;444\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTa TMT, Zieger A, Schomerus G, Cao TD, Dettling M, Do XT, Mungee A, Diefenbacher A, Angermeyer MC, Hahn E (2016) Influence of urbanity on perception of mental illness stigma: A population based study in urban and rural Hanoi, Vietnam. Int J Soc Psychiatry 62(8):685\u0026ndash;695\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChan KY, Zhao F-f, Meng S, Demaio AR, Reed C, Theodoratou E, Campbell H, Wang W, Rudan I (2015) Urbanization and the prevalence of schizophrenia in China between 1990 and 2010. World Psychiatry 14(2):251\u0026ndash;252\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaraceno B, van Ommeren M, Batniji R, Cohen A, Gureje O, Mahoney J, Sridhar D, Underhill C (2007) Barriers to improvement of mental health services in low-income and middle-income countries. Lancet 370(9593):1164\u0026ndash;1174\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang LH, Phillips MR, Li X, Yu G, Grivel MM, Zhang J, Shi Q, Ding Z, Pang S, Susser E (2022) Determinants of never-treated status in rural versus urban contexts for individuals with schizophrenia in a population-based study in China. BMC Psychiatry 22(1):128\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHou C-L, Chen M-Y, Cai M-Y, Chen Z-L, Cai S-B, Xiao Y-N, Jia F-J (2018) Antipsychotic-free status in community-dwelling patients with schizophrenia in China: Comparisons within and between rural and urban areas. J Clin Psychiatry 79(3):17m11599\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVan NHN, Thi Khanh Huyen N, Hue MT, Luong NT, Quoc Thanh P, Duc DM, Thi Thanh Mai V, Hong TT (2021) Perceived barriers to mental health services among the elderly in the rural of Vietnam: A cross sectional survey in 2019. Health Serv Insights 14(6):1\u0026ndash;10\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMohamed A, Mansoor S (2024) Challenges and opportunities in the mental health landscape of the Maldives. Australasian Psychiatry 32(5):1\u0026ndash;2\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaw H-W, Owens V, Morales SA, Rodriguez N, Kern C, Bach RL (2023) Population mental health in Burma after 2021 military coup: online non-probability survey. BJPsych Open 9(5):e156\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee H, Robinson C, Kim J, McKee M, Cha J (2020) Health and healthcare in North Korea: A retrospective study among defectors. Confl Health 14(1):41\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNishi D, Ishikawa H, Kawakami N (2019) Prevalence of mental disorders and mental health service use in Japan. J Neuropsychiatry Clin Neurosci 73(8):458\u0026ndash;465\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNishi D, Susukida R, Usuda K, Mojtabai R, Yamanouchi Y (2018) Trends in the prevalence of psychological distress and the use of mental health services from 2007 to 2016 in Japan. J Affect Disord 239(10):208\u0026ndash;213\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKovess-Masfety V, Karam E, Keyes K, Sabawoon A, Sarwari BA (2022) Access to care for mental health problems in Afghanistan: A national challenge. Int J Health Policy Manage 11(8):1442\u0026ndash;1450\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchwartz L, Lane H, Hassanpoor Z (2023) Overview and understanding of mental health and psychosocial support in Afghanistan. Int Health 15(5):601\u0026ndash;607\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNaveed S, Waqas A, Chaudhary AMD, Kumar S, Abbas N, Amin R, Jamil N, Saleem S (2020) Prevalence of common mental disorders in south asia: A systematic review and meta-regression analysis. Front Psychiatry 11(9):573150\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOgawa N, Mansor N, Lee S-H, Abrigo MRM, Aris T (2021) Population aging and the three demographic dividends in Asia. Asian Dev Rev 38(1):32\u0026ndash;67\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVassos E, Pedersen CB, Murray RM, Collier DA, Lewis CM (2012) Meta-analysis of the association of urbanicity with schizophrenia. Schizophr Bull 38(6):1118\u0026ndash;1123\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi J, Rose N (2017) Urban social exclusion and mental health of China's rural-urban migrants \u0026ndash; A review and call for research. Health Place 48(11):20\u0026ndash;30\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi L, Wang H-m, Ye X-j, Jiang M-m, Lou Q-y, Hesketh T (2007) The mental health status of Chinese rural\u0026ndash;urban migrant workers. Soc Psychiatry Psychiatr Epidemiol 42(9):716\u0026ndash;722\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSagar R, Pattanayak RD, Chandrasekaran R, Chaudhury PK, Deswal BS, Lenin Singh RK, Malhotra S, Nizamie SH, Panchal BN, Sudhakar TP et al (2017) Twelve-month prevalence and treatment gap for common mental disorders: Findings from a large-scale epidemiological survey in India. Indian J Psychiatry 59(1):46\u0026ndash;55\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePutri AK, Gustriawanto N, Rahapsari S, Sholikhah AR, Prabaswara S, Kusumawardhani AC, Kristina SA (2021) Exploring the perceived challenges and support needs of Indonesian mental health stakeholders: A qualitative study. Int J Mental Health Syst 15(1):81\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaramis A, Van Tuan N, Minas H (2011) Mental health in southeast Asia. Lancet 377(9767):700\u0026ndash;702\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaddock A, Blair C, Ean N, Best P (2021) Psychological and social interventions for mental health issues and disorders in Southeast Asia: a systematic review. Int J Mental Health Syst 15(1):56\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang Z, Sun K, Jatchavala C, Koh J, Chia Y, Bose J, Li Z, Tan W, Wang S, Chu W et al (2020) Overview of Stigma against Psychiatric Illnesses and Advancements of Anti-Stigma Activities in Six Asian Societies. Int J Environ Res Public Health vol 17:280\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVaishnav M, Javed A, Gupta S, Kumar V, Vaishnav P, Kumar A, Salih H, Levounis P, Ng B, Alkhoori S et al (2023) Stigma towards mental illness in Asian nations and low-and-middle-income countries, and comparison with high-income countries: A literature review and practice implications. Indian J Psychiatry 65(10):995\u0026ndash;1011\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWittevrongel E, Kessels R, Everaert G, Vrijens M, Danckaerts M, van Winkel R (2025) A user perspective on youth mental health services: Increasing help-seeking behaviour requires addressing service preferences and attitudinal barriers. Early Interv Psychiat 19(1):e13584\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrian RM, Ben-Zeev D (2014) Mobile health (mHealth) for mental health in Asia: Objectives, strategies, and limitations. Asian J Psychiatry 10:96\u0026ndash;100\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIto H, Setoya Y, Suzuki Y (2012) Lessons learned in developing community mental health care in East and South East Asia. World Psychiatry 11(3):186\u0026ndash;190\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Schizophrenia, Burden of disease, Asia, Prevalence, Incidence, Years lived with disability, Socio-demographic Index","lastPublishedDoi":"10.21203/rs.3.rs-6476890/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6476890/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eSchizophrenia is a severe mental disorder imposing a substantial burden worldwide. Understanding its impacts and trends in Asia is crucial for devising effective intervention. This study quantified the prevalence, incidence, and years lived with disability (YLDs) rates of schizophrenia across Asian regions, examine their trends, and explore the relationship between socio-demographic index (SDI) and YLDs rates.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eData from Global Burden of Disease (GBD) study (1990\u0026ndash;2021) were analyzed by age, sex, region, and SDI levels. Age-standardized YLDs rates were assessed using the estimated annual percentage change (EAPC), while future trends were forecasted using the Bayesian age-period-cohort (BAPC) model. The correlation between age-standardized YLD rates and SDI was also examined.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eSchizophrenia prevalence in Asia rose from 8.42\u0026nbsp;million cases in 1990 to 14.96\u0026nbsp;million in 2021, with higher rates in males. Incidence increased by 32.76%, and in 2021 schizophrenia accounted for 5.45\u0026nbsp;million YLDs, peaking in aged 35\u0026ndash;39 years. Vietnam reported the highest age-standardized YLD rates, followed by China, Taiwan, and the Maldives. EPAC trends indicated rising burdens in Myanmar and the Maldives, while declines occurred in North Korea and Pakistan. A positive correlation between the SDI levels and age-standardized YLD rates was identified, with forecasts predicting a continued rise in schizophrenia-related YLDs in Asia over the next three decades.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe burden of schizophrenia in Asia has grown markedly over the past three decades. Urgent evidence-based policies are needed to improve early detection, ensure equitable access to mental healthcare, and reduce regional disparities.\u003c/p\u003e","manuscriptTitle":"Trends and burden of schizophrenia in Asia: Insights from the global burden of disease study 2021","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-13 06:31:21","doi":"10.21203/rs.3.rs-6476890/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9dfb5102-3af1-476a-9aef-2183e0f8e031","owner":[],"postedDate":"May 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-27T14:34:57+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-13 06:31:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6476890","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6476890","identity":"rs-6476890","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}