Patients with SCZ admitted to our hospital from June, 2020 to June, 2021 were retrospectively collected as research subjects. Of these, 80 patients were treated with paliperidone and 36 patients were treated with paliperidone combined with sertraline. 1:1 propensity score matching (PSM) was used to balance the influence of confounding factors among the groups, and three covariables were selected for 1:1 matching (gender, age, positive and negative symptom scale (PANSS) score). Finally, 36 cases of paliperidone combined with sertraline and 36 cases of paliperidone were successfully matched. This study was reviewed and approved by the medical ethics committee of the hospital (number: 2023001-03).

Inclusion criteria: (1) Relevant examinations were completed after admission and the patients were in line with the International Classification of Diseases, 10th Revision (ICD-10) Classification of Mental and Behavioral Disorders [12]. (2) The patient had not taken paliperidone or sertraline in the recent period. (3) PANSS score was $\ge$60 points. (4) No congenital mental disorders were present and the patient had adequate communication skills. (5) Patient data were complete.

Exclusion criteria: (1) Patients with heart, liver, lung, and other malignant tumors. (2) Allergies to paliperidone, sertraline, or other drugs. (3) Patients with serious self-injury or severe suicidal tendencies. (4) Patients with organic diseases. (5) A family history of epilepsy. (6) Accompanying central nervous system disease. (7) Chronic alcoholism. (8) Lactating and pregnant women.

Control group patients received paliperidone (SFDA approval number H20203265, specification: 3 mg, Jiangsu Haosen Pharmaceutical Group Co., Ltd., Lianyungang, China) as a daily morning dose, 3 mg/d, according to the patient’s tolerance to the drug and their own ability to adjust the dose, increasing to 6–12 mg/d, once every morning. The observation group were given sertraline (SFDA approval number H20060364, specification: 50 mg, Guangzhou Baiyunshan Guanghua Pharmaceutical Co., Ltd., Guangzhou, China) in addition to the drug regimen of the control group, once a day, 50 mg each time. One week later, according to the patient’s ability to increase the drug dose, the dose was increased to 100 mg/d. The dose could be further increased or decreased as appropriate, with the maximum dose not to exceed 200 mg. Both groups were treated for 8 weeks.

The clinical efficacy of the two groups after treatment was compared. The evaluation criteria were as follows [13]: Cured: after 12 weeks of treatment, patients’ PANSS scores were more than 75% lower than before treatment. Significant improvement: the PANSS score decreased by 50% or more and less than 75% after treatment. Improvement: the PANSS score decreased by 25% or more and less than 50% after treatment. Ineffective: the PANSS score decreased by less than 25% after treatment. Total response rate = (cure + significant improvement + improvement) cases/total cases $\times$ 100%.

To compare the quality of life before and after treatment between the two groups, schizophrenia quality of life scale (SQLS) was used [14], which included assessment of material life, physical function, psychological function, and social function. Each dimension uses a percentage system. The higher the score, the better the quality of life of patients.

Before and after treatment, 6 mL of fasting elbow vein blood was collected from the two groups, and the supernatant was extracted after centrifugation. The levels of neuron-specific enolase (NSE) (ml060406, Shanghai Enzyme-linked Biotechnology Co., Ltd., Shanghai, China), neuregulin 1 (NRG1) (ml024389, Shanghai Enzyme-linked Biotechnology Co., Ltd., Shanghai, China), glutamic oxalic aminotransferase (AST) (ml095196, Shanghai Enzyme-linked Biotechnology Co., Ltd., Shanghai, China), total bilirubin (TBiL) (M1224L, Shanghai Enzyme-linked Biotechnology Co., Ltd., Shanghai, China), and alanine aminotransferase (ALT) (ml095164, Shanghai Enzyme-linked Biotechnology Co., Ltd., Shanghai, China) levels were measured using enzyme-related immunosorbent assay. Liver function index AST normal value: 0~50 U/L; TBiL normal value: 5.0~21.0 µmol/L; ALT normal value: 0~50 U/L. A detection value of each index exceeding the upper limit of the normal value indicates abnormal liver function. For obvious liver function abnormalities, that is, when the value is more than 2 to 3 times the normal value, liver protection drugs should be used.

Five milliliters of blood were drawn in a test tube without anticoagulants, coagulated naturally at room temperature for 20 min, then centrifuged at 3000 r/min to isolate the serum, which was stored at –80 °C until it was removed for cytokine analysis. Tumor necrosis factor $\alpha$ (TNF-$\alpha$) (ab309419, Abcam, Cambridge, UK), interleukin-6 (IL-6) (ab178013, Abcam, Cambridge, UK), and interleukin-2 (IL-2) (ab100566, Abcam, Cambridge, UK) levels were measured using enzyme-linked immunosorbent assay (ELISA).

The Hamilton Anxiety Scale (HAMA) and the Hamilton Depression Scale (HAMD) were used to evaluate the anxiety and depression levels of the two groups of patients before and after the intervention. The scores of both are inversely proportional to their levels, with the higher the score, the more serious the anxiety and depression levels of the patients [15].

Differences in scores and percentage changes for measurements were calculated to determine the baseline changes and the difference between groups. Difference in score = score after treatment – score before treatment. Percentage change = [((measurement after treatment – measurement before treatment)/measurement Before treatment) $\times$ 100]. Comparisons were made between groups according to these differences in scores and percentage changes.

By referring to the adverse reaction return sheet, the adverse reactions in the course of clinical treatment were statistically analyzed and the adverse reactions were recorded.

SPSS v26.0 software (IBM, Armonk, NY, USA) was used for statistical analysis. Continuous data were represented by mean $\pm$ standard deviation (SD), as used for SQLS and HAMA scores. The independent sample t-test was used for comparison between groups, and the paired t-test was used for comparison of before and after treatment. Categorical data were represented by n (%), and the comparison between groups was tested by the $\chi$² test. p 0.05 was considered to be statistically significant.

Observation group: 19 males and 17 females, ranging in age from 26 to 40 years, with a mean age of (32.44 $\pm$ 3.22) years, the course of disease was (11.13 $\pm$ 2.12) years, and the total PANSS score was (75.63 $\pm$ 6.37). Control group: 21 males and 15 females, ranging in age from 25 to 39 years, with a mean age of (32.19 $\pm$ 3.79) years, the course of disease was (12.01 $\pm$ 2.27) years, and the total PANSS score was (75.70 $\pm$ 6.87). There was no significant difference in general data (gender, age, course of disease, and PANSS score) between the two groups (p = 0.635, p = 0.764, p = 0.094, p = 0.964).

The total effective rate of the observation group [n = 34 (94.44%)] was significantly higher than that of control group [n = 26 (72.22%)] (p = 0.011), as shown in Table 1.

Before treatment, there were no significant differences in the scores for material life, physical function, psychological function, and social function between the two groups (p = 0.624, p = 0.755, p = 0.810, p = 0.617). After treatment, the scores for material life, physical function, psychological function, and social function in two groups were higher than before treatment (p 0.001), and in the observation group they were higher than in the control group (p 0.001), as shown in Table 2.

Before treatment, there were no significant differences in NSE and NRG1 levels between the two groups (p = 0.793, p = 0.689). After treatment, NSE was significantly decreased in both groups (p 0.001), and in the observation group it was significantly lower than in the control group (p 0.001). NRG1 was significantly increased in both groups (p 0.001), and in the observation group it was significantly higher than in the control group (p 0.001), as shown in Table 3.

Before treatment, there were no significant differences in liver function indexes AST, TBiL, and ALT between the two groups (p = 0.331, p = 0.198, p = 0.479). After treatment, AsT, TBiL, and ALT levels were significantly increased in both groups (p 0.001). However, the values of these liver function indicators were still within the normal range, as shown in Table 4.

As shown in Table 5, serum levels of TNF-$\alpha$, IL-6, and IL-2 in both groups after treatment were lower than before treatment (p 0.001). After treatment, the levels of TNF-$\alpha$, IL-6, and IL-2 in the observation group were significantly lower than those in the control group (p 0.001).

Before treatment, there were no significant differences in HAMA and HAMD scores between the two groups (p = 0.856, p = 0.344). After treatment, HAMA and HAMD scores in both groups were significantly decreased (p 0.001), and in the observation group they were significantly lower than in the control group (p 0.001), as shown in Table 6.

Differences in scores and percentage changes in measurements were compared between the two groups before and after treatment. Differences in scores for material life, physical function, psychological function, social function, and HAMA and HAMD were found. The differences in scores in the observation group were greater than those in the control group (p 0.001). The percentage changes of neural function related factors and inflammatory cytokines were greater in the observation group than in the control group (p 0.001). There was no statistical significance in the percentage changes of AST, TBiL, and ALT levels between the two groups (p = 0.673, p = 0.574, p = 0.787). Table 7 shows this.

During the treatment, one case of dizziness occurred in the observation group, and one case of headache and two cases of dizziness occurred in the control group. After the treatment, all patients were cured and there were no other complications or obvious side effects.