Table 1 summarized the daily hospitalization for schizophrenia and meteorological variables. During the 15-year study period, there were 21,169 cases of schizophrenia in warm season. The daily mean count of schizophrenic admissions was 9.2. The number of male cases was slightly less than female. In terms of age group, the count of patients under 40 years old (14,637) was about twice that of over 40 years old (6,532). The daily mean temperature, relative humidity and DTR of the warm season were 25.8°C, 77.2% and 7.9°C, respectively. The average daily concentrations of PM2.5, NO2, SO2, CO and O3 were 44.5 µg/m3, 30.9 µg/m3, 10.7 µg/m3, 0.8 µg/m3, 109.0 µg/m3, respectively. The daily average value of DEHH and IQR were 154.4°C and 129.8°C, respectively. The hourly maximum temperature was 41.0°C and the minimum temperature was 9.0°C during the whole study period. Figure 1 showed the time trend distribution of DEHH, mean temperature and schizophrenia cases during the warm season of 2005–2019 in Hefei, China.
Table 1
Descriptive statistics of daily hospitalization for schizophrenia and meteorological variables during the warm season (May-September) of 2005–2019 in Hefei, China.
Variables
|
Sum
|
Mean ± SD
|
Min
|
P25
|
P50
|
P75
|
Max
|
Schizophrenia cases
|
21,169
|
9.2 ± 3.84
|
0
|
7
|
9
|
12
|
28
|
Gender
|
|
|
|
|
|
|
|
Male
|
10,538
|
4.6 ± 2.48
|
0
|
3
|
4
|
6
|
17
|
Female
|
10,631
|
4.6 ± 2.46
|
0
|
3
|
4
|
6
|
16
|
Age
|
|
|
|
|
|
|
|
0–40 years old
|
14,637
|
6.4 ± 2.98
|
0
|
4
|
6
|
8
|
21
|
> 40 years old
|
6,532
|
2.8 ± 1.86
|
0
|
1
|
3
|
4
|
12
|
Meteorological variables
|
|
|
|
|
|
|
|
Mean temperature (°C)
|
-
|
25.8 ± 3.8
|
14.0
|
23.0
|
26.0
|
28.9
|
35.5
|
Maximum temperature (°C)
|
-
|
29.8 ± 4.3
|
16.0
|
27.0
|
30.0
|
33.0
|
41.0
|
Minimum temperature (°C)
|
-
|
21.9 ± 3.9
|
9.0
|
19.0
|
22.0
|
25.0
|
31.0
|
Relative humidity (%)
|
-
|
77.2 ± 11.3
|
30.0
|
70.0
|
78.0
|
85.0
|
100.0
|
DTR (°C)
|
-
|
7.9 ± 3.0
|
1.0
|
6.0
|
8.0
|
10.0
|
18.6
|
DEHH (°C)
|
-
|
154.5 ± 83.5
|
0.0
|
88.4
|
153.6
|
218.2
|
366.8
|
PM2.5 (µg/m3) a
|
-
|
44.5 ± 83.5
|
5.0
|
26.0
|
39.0
|
55.0
|
289.0
|
NO2 (µg/m3) a
|
-
|
30.9 ± 11.8
|
8.0
|
22.0
|
29.0
|
37.0
|
92.0
|
SO2 (µg/m3) a
|
-
|
10.7 ± 5.7
|
2.0
|
6.5
|
10.0
|
13.0
|
43.0
|
CO (µg/m3) a
|
-
|
0.8 ± 0.2
|
0.3
|
0.6
|
0.7
|
0.9
|
2.1
|
O3 (µg/m3) a
|
-
|
109.0 ± 46.7
|
13.0
|
72.0
|
106.0
|
141.0
|
264.0
|
a Data of air pollutants were obtained in Hefei, China during 2013–2019. |
SD: Standard Deviation; DEHH: Daily excess heat hourly.
Figure 2 showed the lag effects of each IQR increment in DEHH on total schizophrenia hospitalizations and subgroups. The effects of DEHH on total schizophrenia admissions appeared at lag 1 (RR = 1.036, 95% CI: 1.016, 1.057), and persisted up to lag 4 (RR = 1.025, 95% CI: 1.005, 1.046) (data were shown in Table 2). Subgroup analyses by gender illustrated that the effect of DEHH on male schizophrenics was from lag 0 (RR = 1.059, 95% CI: 1.005, 1.116) to lag 3 (RR = 1.036, 95% CI: 1.006, 1.067) (Fig. 2b). However, we did not find a significant association between DEHH and female schizophrenics (Fig. 2c). For cases over 40 years old, DEHH presented significant effect from lag 1 (RR = 1.049, 95% CI: 1.011, 1.087) to lag 3 (RR = 1.039, 95% CI: 1.011, 1.077) (Fig. 2d). For cases under 40 years old, we didn’t observe a significant association (Fig. 2e). The exposure-response relationship of DEHH on total schizophrenic admissions and subgroups were shown in Supplementary Fig. 2. Table 3 showed the cumulative effects of DEHH on total schizophrenia hospitalizations and subgroups from lag 0–0 to lag 0–7. For total cases, the greatest RR of the cumulative effects was 1.189 (95% CI: 1.051, 1.279) at lag 0–5. Meanwhile, the cumulative effects of DEHH on schizophrenia hospitalizations was found only in males and cases over 40 years old in subgroup analyses.
Table 2
The single-day relative risk (RR) estimates of each increment of interquartile range (IQR, 129.8°C) in daily excess heat hourly (DEHH) on total schizophrenia hospitalizations and subgroups during the warm season of 2005–2019 in Hefei, China.
Single-day
|
Relative risks (95% confidence intervals)
|
Total
|
Male
|
Female
|
0–40 years old
|
> 40 years old
|
Lag 0
|
1.033(0.997,1.070)
|
1.059(1.005,1.116)
|
0.998(0.949,1.049)
|
1.007(0.961,1.054)
|
1.050(0.985,1.119)
|
Lag 1
|
1.036(1.016,1.057)
|
1.053(1.022,1.084)
|
1.010(0.981,1.039)
|
1.015(0.9901.042)
|
1.049(1.011,1.087)
|
Lag 2
|
1.037(1.021,1.054)
|
1.045(1.021,1.070)
|
1.019(0.996,1.042)
|
1.022(1.000,1.043)
|
1.046(1.016,1.076)
|
Lag 3
|
1.034(1.014,1.055)
|
1.036(1.006,1.067)
|
1.022(0.994,1.051)
|
1.023(0.997,1.051)
|
1.039(1.001,1.077)
|
Lag 4
|
1.025(1.005,1.046)
|
1.023(0.993,1.054)
|
1.017(0.989,1.046)
|
1.018(0.991,1.045)
|
1.027(0.991,1.065)
|
Lag 5
|
1.010(0.994,1.026)
|
1.007(0.983,1.030)
|
1.004(0.981,1.027)
|
1.005(0.985,1.025)
|
1.010(0.982,1.040)
|
Lag 6
|
0.991(0.972,1.010)
|
0.989(0.961,1.017)
|
0.985(0.958,1.013)
|
0.987(0.965,1.010)
|
0.990(0.956,1.025)
|
Lag 7
|
0.970(0.938,1.004)
|
0.970(0.923,1.020)
|
0.964(0.919,1.011)
|
0.967(0.928,1.009)
|
0.969(0.911,1.030)
|
Bold font indicated that the results are statistically significant (p < 0.05). |
Table 3
The multi-day relative risk (RR) estimates of each increment of interquartile range (IQR, 129.8°C) in daily excess heat hourly (DEHH) on total schizophrenia hospitalizations and subgroups during the warm season from 2005–2019 in Hefei, China.
Multi-day
|
Relative risks (95% confidence interval)
|
Total
|
Male
|
Female
|
0–40 years old
|
> 40 years old
|
Lag 0–0
|
1.033 (0.997,1.070)
|
1.059 (1.005,1.116)
|
0.998 (0.949,1.049)
|
1.006 (0.961,1.054)
|
1.050 (0.985,1.119)
|
Lag 0–1
|
1.071 (1.014,1.130)
|
1.115 (1.029,1.208)
|
1.007 (0.933,1.087)
|
1.022 (0.953,1.097)
|
1.101 (0.998,1.213)
|
Lag 0–2
|
1.111 (1.045,1.181)
|
1.165 (1.064,1.276)
|
1.026 (0.941,1.120)
|
1.045 (0.965,1.131)
|
1.151 (1.030,1.285)
|
Lag 0–3
|
1.149 (1.077,1.225)
|
1.207 (1.097,1.327)
|
1.049 (0.956,1.152)
|
1.069 (0.983,1.162)
|
1.196 (1.064,1.344)
|
Lag 0–4
|
1.177 (1.099,1.261)
|
1.234 (1.114,1.366)
|
1.068 (0.966,1.180)
|
1.088 (0.994,1.191)
|
1.228 (1.083,1.393)
|
Lag 0–5
|
1.189 (1.105,1.279)
|
1.242 (1.114,1.384)
|
1.072 (0.963,1.194)
|
1.093 (0.993,1.204)
|
1.241(1.086,1.418)
|
Lag 0–6
|
1.178 (1.093,1.270)
|
1.228 (1.099,1.372)
|
1.056 (0.943,1.183)
|
1.079 (0.978,1.191)
|
1.229 (1.070,1.410)
|
Lag 0–7
|
1.143 (1.052,1.242)
|
1.192 (1.054,1.347)
|
1.018 (0.896,1.156)
|
1.044 (0.938,1.162)
|
1.190 (1.022,1.386)
|
Bold font indicated that the results are statistically significant (p < 0.05). |
Fig. 3 demonstrated the temporal variation in the cumulative effects of DEHH on schizophrenia hospitalizations during the warm season of 2005-2019 in Hefei, China. A consistent and clear temporal variation pattern was observed at lag 0-4 and lag 0-7. At lag 0-7, hospitalization for schizophrenia was found to be the strongest associated with DEHH in the period of 2010-2012 (RR=1.505, 95% CI: 1.186, 1.909). Besides, Fig. 3 indicated that DEHH was more strongly associated with hospitalization for schizophrenia in the middle stage of the entire study period (data were shown in Supplementary Table 1). In total, the cumulative effects of DEHH represented a complex change, showing a tendency of early upward and later downward.
Figure 4 presented the effects of temperature observation time on heat-schizophrenia relationships in warm season from lag 1 to lag 5. The RR estimates by each IQR increment were statistically significant from 0 am at lag 1 (RR = 1.034, 95% CI: 1.013, 1.054) to 3 am at lag 3 (RR = 1.024, 95% CI: 1.010, 1.039). Overall effects of temperature observation time on heat-schizophrenia were gradually decreased from lag 1 to lag 5, and almost no statistical significance was observed after lag 4 (the RR estimates were not shown in the figure at lag 6 and lag 7). In short, Fig. 4 showed the impacts of heat on hospitalization for schizophrenia varied with the time from lag 1 to lag 5, and the strongest association occurred at 5 am at lag 1 (RR = 1.045, 95% CI: 1.025, 1.066). Our results suggested that there may be a stronger association between heat and schizophrenia at dawn (0 am-6 am) (data were shown in Supplementary Table 2). In addition, in order to reflect the integrity of the effect of heat on the admissions for schizophrenia, we presented the RR estimates of lag 0 in Supplementary Fig. 3. However, the hourly temperature effect pattern on the day of onset (lag 0) should be carefully interpreted, as temperature "exposure" measurement on that day may occur after hospitalizing (Davies, et al. 2016).
Our findings remain stable through varying the degrees of freedom for relative humidity (3–5 df), DTR (3–5 df), the seasonality and long-term trend (3–5 df) (Supplementary Fig. 4). We found similar estimates of heat effects before and after controlling for the air pollutants (Supplementary Table 3). Furthermore, in the time-stratified analysis, the overall trend was consistent after splitting the time period into an interval of 4 and 5 years (Supplementary Fig. 5 and Fig. 6).