SCZ is a chronic, severe psychiatric disorder characterized by persistent disruptions in cognition, perception, emotion, and social functioning (1, 2). With a typical onset in late adolescence or early adulthood, it contributes to lifelong disability and is associated with high personal and societal costs (3). Globally, the lifetime prevalence of SCZ is approximately 1%, and individuals with the disorder often face significantly reduced life expectancy due to comorbid physical ill While they offer valuable foundational data for understanding the epidemiology ness and elevated suicide risk (4, 5). According to the GBD 2021, the DALY burden attributable to mental disorders was ranked 19th in 1990 and rose to 6th in 2021 (6), highlighting the global intensification of the mental health crisis. Descriptive epidemiological studies on the incidence, prevalence, and mortality of SCZ are essential for comprehensively understanding the current epidemiological landscape of the disorder and play a critical role in informing the planning and allocation of mental health services in public health systems (7). Although numerous studies have examined age-, sex-, and region-specific epidemiological characteristics of individuals with SCZ (8–11), most of these investigations are based on global or Western populations, with limited consideration of China’s unique sociocultural and demographic context.

In China, several cross-sectional studies have shown the prevalence of SCZ at the provincial level using diagnostic tools such as the Structured Clinical Interview for DSM (SCID) or the Composite International Diagnostic Interview (CIDI) (12). Although the global burden of SCZ has been widely studied, China’s unique social structure and stage of development present distinct epidemiological patterns and intervention challenges. Long-standing socioeconomic and healthcare resource disparities between urban and rural areas in China are associated with significant differences in environmental exposure, accessibility to medical services, and treatment outcomes for patients with schizophrenia. Existing studies have reported that patients with schizophrenia in rural areas tend to have higher mortality rates and may be more vulnerable to external stressors such as climate change (13, 14). In addition, the processes of urbanization and population mobility have been linked to increased psychological stress, with social isolation and adaptation difficulties among migrant populations identified as important ecological correlates and risk factors associated with schizophrenia (15). Prior research using national-level data, such as the GBD Study, has laid important groundwork in characterizing SCZ burden in China (16). However, updated analyses after 2020 and long-term forecasts remain limited, highlighting the need for continued research to support future policy directions. While existing studies provide valuable data on SCZ epidemiology in China, there is a notable lack of studies using predictive modeling tailored to China’s unique socioeconomic and demographic features to estimate the future burden of SCZ. This gap hampers the formulation of forward-looking interventions and evidence-based mental heal specifically tailored to China’s socioeconomic and demographic context policies. Therefore, there is a pressing need for locally grounded research that integrates temporal trends, regional disparities, and disease burden forecasting to better inform mental health policy and service planning in China. To address the current limitations in SCZ epidemiological research in China, this study aims to conduct a comprehensive analysis based on data from the Global Burden of Disease (GBD) 2021 study. The GBD project, led by the Institute for Health Metrics and Evaluation (IHME), is a large-scale global epidemiological initiative designed to assess and compare the burden of diseases, injuries, and risk factors across countries and regions. The GBD provides authoritative data to support public health decision-making worldwide, and its multi-decade continuity enables robust long-term trend analysis.

Therefore, this study aimed to (1) assess the long-term trends of SCZ burden in China from 1990 to 2021 using GBD 2021 data (2); identify key temporal inflection points in burden indicators through Joinpoint regression analysis (3); compare these trends with global patterns by sex and age group; and (4) project future trends of ASIR, ASPR, and ASDR in China up to 2050 using the Bayesian age–period–cohort (BAPC) model. Our findings may inform precision public health strategies and resource allocation for SCZ prevention and management in China.

This study provides a comprehensive and systematic evaluation of the temporal trends in the burden of SCZ in China from 1990 to 2021, with projections extending into the 2050. While the ASIR in China has remained largely stable over the past three decades, both the ASPR and ASDR have shown persistent upward trends, reflecting the chronic and disabling nature of SCZ. Importantly, these increases are not evenly distributed across populations: females exhibited faster growth in both ASPR and ASDR than males, and this divergence is projected to widen in the coming decades. Furthermore, the burden of SCZ is increasingly concentrated in midlife adults-especially those aged 40–59 years-indicating a demographic shift in disease impact. These findings reveal the evolving landscape of SCZ burden in China and underscore the urgency of developing age- and gender-sensitive mental health policies.

From 1990 to 2021, the ASIR of SCZ in China remained relatively stable with a slight upward trend, contrasting with a global decline. Previous studies have shown that the global ASIR of SCZ may be related to SDI, with high-SDI countries generally experiencing increases in incidence and disease burden, while low-SDI countries tend to have stable or declining ASIR (9). As a high-middle SDI country, China fits this pattern in ASIR but stands out for rising ASPR and ASDR. This may result from improved case detection, reduced stigma, increased awareness, and better psychiatric infrastructure, especially in urban areas. Additionally, policy focus on severe mental illness may enhance surveillance and inflate the recorded burden (9, 15). The ASPR and ASDR showed sustained increases and are projected to rise further through 2050. This reflects the accumulating burden of SCZ as a chronic psychiatric disorder and the escalating challenges faced by long-term prevention and control efforts. The rising ASPR likely reflects better diagnosis and longer survival due to improved access to treatment and community-based care-yet these advances may not restore function (20). The continued increase in ASDR may also stem from treatment gaps and common comorbidities such as depression, substance use, and metabolic disorders, which worsen disability. Thus, stable incidence should not be seen as epidemiological progress when chronic symptoms and care disparities persist. India exhibits a relatively high prevalence of schizophrenia spectrum disorders but faces a significant treatment gap (approximately 72%), with socioeconomic factors such as low education levels and unemployment substantially increasing the disease burden (21). Brazil shows marked urban-rural differences in incidence rates, and insufficient mental health service coverage in rural areas exacerbates the disease burden (22). In contrast, China’s burden is more influenced by rapid urbanization and healthcare system reforms. These differences reflect the diversity in sociocultural contexts and healthcare resource allocation among LMICs, highlighting the need for policy interventions tailored to each country’s specific conditions.

Sex differences in the burden of SCZ are well-established and reflected in global and national disease burden data. Males exhibit higher incidence, mortality, and DALYs than females (5, 8, 23). This study validates prior observations and confirms the continuing sex-specific differences in SCZ burden. Notably, the rate of increase in the ASPR and ASDR among Chinese females has not only exceeded that of males but also surpassed global averages, suggesting a widening sex-based disparity in disease burden. Emerging evidence suggests that the faster increase in SCZ-related prevalence and DALYs among Chinese females may reflect a combination of biological, diagnostic, and sociocultural factors. Estrogen is believed to provide neuroprotection by modulating dopamine pathways and inflammation, helping to alleviate psychotic symptoms (24). However, hormonal fluctuations, particularly declining estrogen levels during perimenopause and menopause, may exacerbate symptoms and raise relapse risk, leading to a higher disease burden in middle-aged women (25). Diagnostic criteria developed predominantly from male samples may overlook female-specific features, such as later onset and greater emotional symptoms, contributing to delayed or missed diagnoses (26–28). Additionally, chronic stressors like caregiving roles, gender-based discrimination, and stigma may hinder help-seeking and worsen outcomes (27, 29). Women also face unique challenges in pharmacological treatment, such as increased sensitivity to side effects and insufficient attention to reproductive health, which may impair adherence and elevate long-term disability (29, 30). These factors may jointly explain the widening sex gap in SCZ burden observed in China and highlight the need for more tailored prevention, diagnosis, and treatment strategies for women. Given our finding that DALYs increased more rapidly among females, we also propose gender-sensitive care strategies, such as mental health education campaigns designed to reduce stigma toward women with psychiatric illness, and family-based psychoeducation that acknowledges the unique caregiving and social roles women often hold in Chinese society. In summary, while males bear a higher absolute burden of schizophrenia, the faster rise in ASPR and ASDR among Chinese females—exceeding both male and global trends—suggests a widening sex disparity. This may reflect hormonal changes, under recognition of female-specific symptoms, greater psychosocial stress, and treatment challenges in women. These findings highlight the need for gender-sensitive mental health policies, including tailored screening, reproductive health support, and improved access to long-term psychosocial care for women, especially during midlife.

Analyzing SCZ patients by different age groups in 2021 revealed that the burden of SCZ in China exhibits a bimodal distribution, with incidence and prevalence peaking during late adolescence to early adulthood (approximately 15 to 40 years), which is considered a critical window for long-term disability burden (16, 31). The neurodevelopmental hypothesis posits that disruptions in brain maturation, such as aberrant synaptic pruning, cortical development, and dopaminergic regulation-which often originate prenatally or in early life, become manifest during adolescence and early adulthood (32–34). Despite growing evidence supporting these mechanisms, early detection and intervention remain insufficient in many countries, particularly within school and primary care settings (2). Therefore, future public health strategies should prioritize these high-risk age groups by implementing structured, school- and community-based screening programs. These should include age-specific mental health assessments-particularly targeting adolescents and young adults-and comprehensive interventions such as cognitive behavioral therapy, family psychoeducation, and enhanced community-based follow-up for individuals at elevated risk. Additionally, culturally sensitive anti-stigma campaigns and personalized pharmacological treatments should be integrated to help delay disease onset and improve long-term clinical outcomes (35, 36). This study also identified a second peak in the male-to-female prevalence ratio of SCZ in China in 2021 among the 60–64 age group. During adolescence, societal gender role expectations and pressures may influence the sensitivity and reporting of diagnoses, while in older adults, differences in social support systems and access to health screenings may further affect diagnosis rates and disease burden. Given the lack of direct biological evidence for this phenomenon, future research should integrate epidemiological, sociocultural, and healthcare system factors to further investigate the underlying causes of this biphasic pattern and its implications for the management of schizophrenia.

Join point analysis revealed a significant turning point in 2016 for both ASPR and ASDR in China, aligning with the implementation of the National Mental Health Work Plan (2015–2020). Between 2009 and 2015, the 686 Program, initiated in 2005, provided free medication and follow-up subsidies (37). The 2015 Mental Health Work Plan and the scaling-up of the 686 Program subsequently expanded community-based screening and improved service accessibility, especially in underserved regions (38, 39). Framed by the stress–vulnerability model, which posits that the onset of schizophrenia results from the interaction between individual vulnerability and chronic environmental stressors, these policy interventions alleviated key stressors-namely economic hardship, geographic barriers, and social stigma—thereby lowering individuals’ threshold for perceiving and reporting symptoms. Consequently, previously undetected cases emerged in the healthcare system. The 2016 inflection should therefore be interpreted as a systematic unmasking of latent cases rather than a true surge in schizophrenia incidence. As Vigo et al. noted, inadequate service coverage leads to substantial under-ascertainment of mental disorders; expanding detection capacity increases reported prevalence without necessarily indicating a rise in true incidence (40). Through the lens of the stress-vulnerability model, we can better understand how policy and societal factors, by modulating stress perception and help-seeking behavior, indirectly shape the spatiotemporal patterns of schizophrenia burden.

From 2019 onwards, the incidence of SCZ began to trend upward, a trend that may be associated with the emergence of the COVID-19 pandemic. Coronaviruses, including SARS-CoV-2, possess neurotropic characteristics that facilitate central nervous system invasion and provoke excessive cytokine release, thereby exacerbating psychiatric manifestations (41). Furthermore, psychosocial stressors induced by the pandemic interact synergistically with inherent neurobiological vulnerabilities, as postulated by the Diathesis-Stress Model (33). Specifically, dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis increases stress sensitivity, resulting in cortisol-mediated dysregulation of dopaminergic and glutamatergic neurotransmission, processes that may precipitate or exacerbate psychotic disorders. Therefore, the pronounced increase in SCZ incidence observed after 2019 is likely attributable to the combined impact of COVID-19-associated neurobiological insults and pandemic-related psychosocial stressors, superimposed upon underlying neurodevelopmental susceptibilities. Beyond neurobiological mechanisms, pandemic-related psychosocial stressors—such as service disruptions, caregiving burdens, and social isolation-may have exacerbated schizophrenia burden, particularly among vulnerable groups (42–44). While the COVID-19 pandemic may be associated with changes in the incidence of schizophrenia, our join point regression analysis did not identify 2019 as a statistically significant breakpoint. This may reflect delayed effects of the pandemic on mental health service utilization and diagnostic reporting, or the possibility that data up to 2021 were insufficient to capture post-pandemic trend changes. Therefore, continued monitoring is warranted to assess the long-term impacts of COVID-19 on the burden of schizophrenia.

Our BAPC model predicts further rises in ASPR and ASDR through 2050, highlighting the urgent need for integrated, long-term mental health services. Specifically, the model forecasts that the disease burden among middle-aged adults will continue to increase after 2022, with the burden among females aged 40 to 59 years projected to surpass that of males in the same age group by 2050. Therefore, we advocate for the expansion of community-based mental health services, including assertive community treatment and mobile outreach teams, to address care continuity and accessibility, especially in underserved rural regions where treatment gaps remain substantial. Therefore, we recommend targeted measures such as piloting rural telepsychiatry services to improve specialist access in underserved areas, expanding community mental health outreach teams to ensure continuity of care, and integrating mental health care into primary health services to facilitate early detection and long-term management.

This study, drawing upon GBD 2021 data and established analytical frameworks, offers a comprehensive and timely assessment of the burden of schizophrenia in China. However, several limitations should be considered when interpreting these findings. First, the GBD 2021 database lacks provincial- and urban-rural stratification, preventing us from capturing regional heterogeneity across China’s vast territory (45). Second, as a secondary analysis, our estimates inherit GBD’s inherent uncertainties—especially under-reporting and variable surveillance quality—which may bias both historical trends and future projections (45). Third, the joinpoint and BAPC models use population-level data and cannot establish causality or account for individual-level risk factors; they also do not adjust for short-term disruptions such as the COVID-19 pandemic. Future work incorporating finer geographic and individual data is needed to refine these national-level trajectories (46). Finally, while this study highlights temporal and demographic trends, future research would benefit from incorporating more granular data on individual-level risk factors, healthcare access, and treatment outcomes.

This study, based on GBD 2021 data and BAPC modeling, provides a comprehensive projection of SCZ burden in China through 2050. While the ASIR is expected to remain stable, both ASPR and ASDR are projected to rise steadily, with the burden increasingly concentrated among midlife adults and notably among females-suggesting a widening gender disparity. The projected ASPR growth also exceeds global averages. These trends highlight the chronic, disabling nature of SCZ and underscore the urgent need for long-term, gender- and age-sensitive strategies. Women, particularly in midlife, may face greater vulnerability due to biological, psychosocial, and treatment-related factors. Policies should prioritize early detection, long-term rehabilitation, and community-based care tailored to female-specific needs. Integrating SCZ prevention into national public health programs-leveraging platforms such as primary care and school-based services-will be essential to improve early access and long-term outcomes. Sustained monitoring and data integration are critical to guide equitable mental health responses.