This longitudinal analysis utilized data from the Global Burden of Disease Study 2021 (GBD 2021), coordinated by the Institute for Health Metrics and Evaluation (IHME). GBD 2021 provides comprehensive, standardized estimates of disease burden for 371 diseases and injuries across 204 countries and territories, including Japan and its 47 prefectures, from 1990 to 2021s (21, 22). Data were accessed via the IHME Global Health Data Exchange (GHDx) (https://vizhub.healthdata.org/gbd-results/). The study assessed the burden of ASD, defined according to GBD 2021 case definitions and mapped to ICD-10 codes (primarily F84) and DSM-5 criteria (1, 2, 21, 22). We extracted data for Japan (overall and by prefecture), the High-Income Asia Pacific region, High Socio-demographic Index (SDI) locations globally, and the Global aggregate for the period 1992–2021. Key outcome metrics extracted were: Prevalence: The total number of individuals living with ASD at a specific point in time (mid-year 2021 for point estimates; annual estimates for trends). Disability-Adjusted Life Years (DALYs): The sum of Years Lived with Disability (YLDs) and Years of Life Lost (YLLs) due to ASD. Given the low premature mortality associated with ASD, DALYs primarily reflect YLDs for this condition (21, 22). Age-Standardized Rates (ASRs): Rates adjusted to the GBD World Standard Population structure to enable comparison across populations with differing age distributions.

The bar chart compares the burden of ASD in Japan’s 47 administrative regions with those in the global, high-SDI and high-income Asia-Pacific regions, showing the results at all ages and after age standardization. We found that prevalence and DALYs were significantly higher than global levels and high SDI regions in almost all administrative regions in Japan, while the high-income Asia-Pacific region was similar to the national burden of disease in Japan. Aomori, Fukuoka, Nagano, and Tokyo have a more prominent disease burden ( Figure 1 ). Further deconstructing the data according to gender, we found that the prevalence rate and DALYs of males were higher than those of females by shown of heatmap ( Supplementary Figure S1 ). Based on the data changes from 1992 to 2021, the prevalence and DALYs trends with time are demonstrated by using area charts and graphs. It can be found that prevalence and DALYs fluctuate over time, but the overall trend is increasing, and the disease group is becoming younger, and the disease burden is increasing in the younger age group ( Figure 2 ). We divided Japanese ASD patients into 47 administrative regions and used a map to show the trend of ASD prevalence and DALYs proportion per capita over time in different administrative regions ( Figure 3A ). A pyramid chart showed the comparison of ASD prevalence and DALYs in different age groups in different administrative regions, which revealed that the peak age group for ASD was 45–49 years old, and a secondary peak age group was 70–74 years old ( Figures 3B, C ). We ranked the disease burden of the 47 administrative regions according to the time-varying trend and performed a paired comparison, which showed that the top four administrative regions, Nagano, Aomori, Fukuoka, and Tokyo, maintained their positions, while the rankings of the remaining 43 administrative regions changed over time ( Figure 3D ). Finally, we used a dual-axis analysis to show the trend relationship between prevalence and ASR, DALYs and ASR over time, which suggested that both prevalence and DALYs were associated with the time trend of ASR ( Figures 3E, F ).

Joinpoint analysis revealed the change trend of disease burden of ASD under different variables (region, gender, age) from 1992 to 2021, and APC and AAPC were calculated for comparison.

The results show that the highest ASPR APC period was 2010-2015, APC=0.89(95%CI:0.85, 0.94), and the lowest ASPR APC period was 2015-2019, APC=-0.47(95%CI: -0.54, -0.4). The highest ASDAR APC period was 2010-2015, APC=0.89(95%CI: 0.85-0.92), and the lowest ASDAR APC period was 2015-2019, APC=-0.45(95%CI: -0.5, -0.4). The national AAPC values of ASPR and ASDAR in Japan from 1992 to 2021 were 0.2744 (95%CI: 0.2606, 0.2882) and 0.2782 (95%CI: 0.2673, 0.2892), respectively. The results were 0.2342 (95%CI: 0.2215, 0.2469) and 0.2362 (95%CI: 0.2248, 0.2475) for males and 0.3177 (95%CI: 0.2978, 0.3375) and 0.3117 (95%CI: 0.2342, 0.2469) and 0.2362 (95%CI: 0.2475) for females. 0.2955, 0.328. The APC and AAPC values of different time stages, regions and genders can be referred to Supplementary Tables S1, S2 . ASPR and ASDAR have increased year by year globally in the past 30 years, and the trend in Japan is close to the same as that in the Asia-Pacific high-income region (AAPC 0.27 vs 0.26), which is much higher than that in the global region and the region with high SDI (AAPC 0.27&0.26 vs 0.06&0.06). This result illustrates the high level of disease burden of ASD in Japan and its region ( Figures 4A, B ). After gender differentiation, it was found that the trend of disease burden indicators of different genders also increased year by year, but the ASPR and ASDAR of males were higher than those of females, indicating that males have always occupied a dominant position in the increasing ASD population in Japan ( Figures 4C, D ). After age differentiation, we found that on the basis of the increase of the overall disease burden index over time, ASPR and ASDAR also increased with the increase of age ( Figure 5 ).

APC analysis decomposed the time dimension into age effect, period effect and cohort effect in order to unpack the independent influence of age, period and cohort. We calculated and plotted the age-period, time-cohort, age-cohort correlation curves with prevalence and DALYs in Japanese ASD patients by sex to determine the impact of different factors on disease burden. On this basis, APC analysis is conducted separately for the whole country and various administrative regions of Japan, and calibration is conducted on different age levels of prevalence and DALYs to provide a targeted analysis and point out the difference of ASD burden among different regions in Japan. From the comparison between stages we found that population prevalence with DALYs increased over time, both overall and by gender. Based on the difference contrasts of Age-cohort effect, we found that over time to 2021, the overall prevalence in Japan exceeded 1500 per 100000 population and DALYs also approached 350 per 100000 population. Among these, the male prevalence is nearly 2500 per 100000 population and DALYs also exceeds 400 per 100000 population, which far exceeds the overall ASD disease burden level in Japan, while the female prevalence is 1000 per 100000 population and DALYs does not exceed 200 per 100000 population ( Figures 6A, B ). However, based on the differential comparison of age-period effect, we found that after structured age, the prevalence and DALYs showed a negative correlation with age, and gradually decreased in both men and women, but the prevalence and DALYs were still much greater than that in women, for example male 2169.72(95%CI:1824.88, 2557.74) vs female 925.52(95%CI:776.29, 1099.33) per 100000 population/male 400.93(95%CI:279.32, 561.28) vs female 169.66(95%CI: 117.37, 234.72) per 100000 population of 50–54 years old people prevalence/DALYs in 2017–2021 and ( Figures 6C, D ). The differential comparison of the effects of period-cohort is consistent with the results of the former two ( Figures 6E, F ). In conclusion, we found that in the APC analysis, the overall disease burden of ASD in Japan increased with the period, showing a trend of young age, and the disease burden of men was much greater than that of women.

We first heat map the Japanese map against the AAPC values of the different administrative regions of Japan, applied the color difference to represent the level of AAPC, and ranked the 47 administrative regions according to the level of AAPC. The results suggested that the top three administrative regions with the highest AAPC were Aichi, Akita and Aomori, indicating that the disease burden of ASD was most significant and should be paid attention to ( Figure 7 ). For a detailed description of the disease burden in these 47 regions, we drew calibration curves by adjusting for the effects of time, period, and cohort. Based on the disease characteristics of ASD, specific age groups (0–4 years) and specific periods (1988-1992) were calibrated and displayed with change curves ( Supplementary Figures S2–S11 ).

We conducted a decomposition analysis to quantify contributions of three drivers to ASD burden changes between 1992 and 2021: Population growth (demographic expansion), Population aging (changing age structure), Epidemiological changes (disorder-specific risk factor prevalence) ( Figure 8 ).

Globally, population growth was the dominant driver of increased ASD burden, accounting for 100.92% of the net prevalence change (+20,077,209 cases) and 102.26% of DALYs increase (+3,758,723 DALYs). This pattern held in high-SDI regions where population growth explained 104.32% of prevalence growth (+2,174,457 cases) and 110.90% of DALYs increase (+403,588 DALYs). Counteracting effects were observed globally: population aging reduced prevalence by 5.85% (-1,163,326 cases) and DALYs by 7.66% (-281,711 DALYs), while epidemiological changes increased prevalence by 4.92% (+979,662 cases) and DALYs by 5.40% (+198,639 DALYs). Similar trends occurred in high-SDI regions where aging reduced prevalence by 17.72% and epidemiological changes increased it by 13.40%. Japan demonstrated a divergent pattern. Population growth contributed moderately to prevalence (+26,831 cases, 55.02%) and DALYs (+4,986 DALYs, 112.50%). Crucially, population aging exerted substantial protective effects, reducing expected prevalence by 310.13% (-151,238 cases) and DALYs by 741.51% (-32,862 DALYs). Conversely, epidemiological changes drove the largest burden increases, accounting for 355.11% of net prevalence change (+173,173 cases) and 729.01% of DALYs change (+32,308 DALYs).

Moreover, the prediction results of the disease burden of ASD in Japan from 2022 to 2050 indicate that the ARIMA model predicted that disease burden prevalence and DALYs decrease annually, while their ASR increases continuously. By 2050, The prevalence prediction value of Japanese ASD in the ARIMA model will be calculated from 1797373.45551684 (1778254.63676399, 1816492.2742697) reduced to 1541547.43833842 (452394.414619911, 2630700.46205692), However, the predicted value of ASPR will be changed from 1458.68139124526 (1443.34004784751, 1474.02273464301) increased to 1720.90869986909 (482.783942768444, 2959.03345696973) ( Figure 9A ). Also, for the DALYs, In the prediction model from 336217.5175970309 in 1990 (328564.755586865, 343870.279607753) reduced to 281936.436409579 (63479.18170497, 500393.691114189), At the same time ASDAR predicted from 274.91919684919635 (268.74443821172, 281.084931627551) upgraded to 324.228788001257 (67.6272352112524, 580.830340791262) ( Figure 9B ).

Multiple epidemiological studies within Japan align with our observed increase in ASD prevalence. Research in Yokohama reported a cumulative incidence of 16.2 per 10,000 and a prevalence of 21.1 per 10,000 for children born in 1988 (3). Similarly, studies in Nagoya and Fukushima-ken documented prevalence rates significantly higher than historical estimates (0.13% and 4.96 per 10,000, respectively), with notable urban-rural gradients (13, 26). This upward trajectory is largely attributable to enhanced detection methods, broader diagnostic practices aligned with evolving criteria (DSM-5-TR, ICD-11), and increased societal and professional awareness. These factors have improved identification, particularly of individuals with milder phenotypes or without co-occurring intellectual disability, who were previously underdiagnosed (27). Furthermore, reduced stigma surrounding neurodevelopmental conditions encourages more families to seek assessment (28).

The escalating prevalence directly translates to a growing societal burden, demanding substantial expansion of specialized educational, healthcare, and support services (29). Our analysis of Age-Standardized Rates (ASR) and Average Annual Percentage Change (AAPC) underscores the severity of the current situation in Japan relative to global, high-SDI, high-income, and other Japanese administrative region averages. The high prevalence of co-existing neurodevelopmental and psychiatric conditions (e.g., reported co-occurrence rates around 3.22% for other NDDs alongside ASD (28)) further amplifies the complexity and resource intensity of required support, necessitating comprehensive, multi-disciplinary care strategies (30). Critically, our projections indicate this burden will continue to rise steadily through 2050, demanding urgent long-term national planning for service provision and workforce training.

A pronounced male predominance in ASD prevalence was consistently observed in our data, mirroring global patterns (approximately 3:1 male-to-female ratio) (31). While biological factors likely contribute significantly to this disparity, evolving diagnostic practices and awareness may also influence detection rates differentially by gender. Females, particularly those without intellectual impairment, may present differently or employ more effective masking strategies, potentially leading to under-identification (7, 10). Our data also reflects a declining age of diagnosis over the study period, indicating improved early detection efforts (28).

Consistent with earlier reports (27), our analysis identified regional heterogeneity within Japan, with higher ASD burden indices often observed in more densely populated or complex urban environments. This pattern may reflect disparities in access to diagnostic services, specialist availability, or heightened parental awareness in urban centers (32), rather than solely indicating environmental etiology. While the search for etiological factors continues, encompassing genetic predispositions and potential environmental influences (e.g., prenatal/perinatal factors implicated in some studies (13, 32)), it is crucial to note that large-scale epidemiological evidence refutes a causal link between vaccines and ASD incidence. The withdrawal of the MMR vaccine in Japan did not alter the upward trajectory of ASD diagnoses (26).

Our projection models, extending the robust GBD methodology (21), indicate a persistent rise in ASD prevalence and associated disability burden in Japan through 2050. This trend aligns with projections for other high-income nations, reflecting the ongoing impact of diagnostic broadening, sustained awareness efforts, and the aging of existing prevalent cases (21, 25). While the GBD 2021 Autism Collaborators highlight the global increase in ASD burden (22), our Japan-specific analysis reveals a burden profile exceeding the averages for high-SDI and high-income regions. This emphasizes the acute and growing challenge ASD presents within the Japanese healthcare and social support systems.