People with schizophrenia have a high prevalence of metabolic syndrome.11 Metabolic syndrome is closely associated with the level of uric acid in patients with schizophrenia.12 However, HUA is poorly studied in patients with schizophrenia. To our best knowledge, the present study is the first study presenting the prevalence and associated risk factors of HUA among Chinese patients with schizophrenia. We found that 42.5% of adult patients with schizophrenia had HUA. Age, duration of schizophrenia, male gender, hypertension, BMI, TC, TG , LDL, and HDL were correlated with uric acid. Furthermore, we found male patients had significantly higher prevalence of HUA than female patients. Patients with HUA were younger, had a higher prevalence of hypertension, had a higher BMI, TC, TG, LDL, and had a lower HDL. Then, binary logistic regression analysis suggested that younger age, hypertension, BMI, TC, TG, and LDL were risk factors for HUA in patients with schizophrenia.
The prevalence of HUA in this study is higher than that reported in studies conducted in the general population in China.2,17 Several factors may account for the higher prevalence of HUA in patients with schizophrenia. The first, abundant studies reported that patients with schizophrenia had a higher prevalence of metabolic syndrome than general population.11 Even the prevalence of metabolic syndrome in drug-naive patients with first episode of schizophrenia was significantly higher than that in health controls (19.1% vs. 6.6%, P<0.001).18 Metabolic syndrome is significant associated with HUA, several studies have even suggested that HUA may be a new marker for metabolic syndrome.19 The second, studies found that antipsychotics were associated increased uric acid and HUA. For example, a study found that the prevalence of HUA increased from 57.5% to 44.7% in adolescent patients with autism spectrum disorder after receiving risperidone.20 Uric acid levels increased with the dose of risperidone and the time of treatment with risperidone. Several studies found that olanzapine was associated with elevated uric acid in patients with schizophrenia, patients with bipolar disorder and healthy subjects.21-24 Though the data of antipsychotics use were not available in our study, most of the patients received antipsychotics treatment before they admitting this hospital. Moreover, risperidone and olanzapine were the most frequently used antipsychotics in Chinese patients with schizophrenia.25 The third, smoking is independently associated with increased prevalence of HUA in the general population.26 A meta-analysis suggested that 59.1% of male patients with schizophrenia in China was current smokers.27 Another meta-analysis reported that female schizophrenic patients had a higher prevalence of current cigarette smoking than that in general population in China.28 The forth, there were regional differences in the prevalence of HUA in China.2 Guangzhou is located in southern of China, while a meta-analysis reported that people in the southern of China had the highest prevalence of HUA in China. The fifth, unhealthy dietary habits and lower of physical activity in patients with schizophrenia may lead to the higher prevalence of HUA. Physical activity was inversely associated with serum uric acid level and sitting time was positively associated with uric acid level.29 Patients with schizophrenia had lower levels of weekly moderate activity and total weekly activity levels than healthy matched controls.30 And in the real world, patients with schizophrenia were more likely to have sedentary behavior than healthy controls.31
The prevalence of HUA was 19.6% in 240 patients with schizophrenia in a French study,15 which was lower than that in the present study. The present study included patients with acute schizophrenia who needed to receive hospitalization, while that study excluded schizophrenic patients with acute episode. Uric acid may decreased from acute to recovery phases in schizophrenia patients.16 Moreover, that study was conducted earlier than our study, while the prevalence of HUA increased in the past years in China. Racial differences may also account for the discrepancy in the prevalence of HUA between the study in France and our study.
Dispute remains over whether age contributes to the risk of HUA. In the general population, a meta-analysis showed that age was associated with HUA.2 However, several studies presented the opposite direction. For example, Dong et al. suggested the prevalence of HUA increased with increasing age in female subjects, but decreased in male subjects.32 A cohort study showed that there were U-shaped or J-shaped associations between HUA prevalence and age.33 In the present study, an interesting finding shows that patients with younger age was associated with increased risk of HUA, which is consistent with studies in Chinese general population .34, 35 Different life styles between people of different generations may partly explain the higher prevalence in younger patients.34 The reasons for the higher prevalence of HUA in younger patients with schizophrenia are still unclear and require further investigations in future.
Agreeing with the study in French patients with schizophrenia,15 we found that male patients had a higher frequency of HUA than female patients. Studies in the general population also found similar results. A meta-analysis even showed male subjects had a twice times higher HUA prevalence than females subjects (21.5% vs. 8.9%) in subjects aged 20 ~ 29 years.2 The uricosuric effects of estrogen in premenopausal females may partly account for the higher prevalence of HUA in males.36 However, a binary logistic regression suggested that male gender was not associated with the prevalence of HUA after adjusting for age, BMI and other factors, which was consistent with studies in the Chinese general population.2 In the study in French patients with schizophrenia,15 males was a risk factor for HUA. That study enrolled 178 males and 62 females. Imbalanced ratio of gender in that study may partly explain the different results between the study in France and our findings.
Our results confirmed previous data that the prevalence of HUA increased with hypertension. A retrospective cross-sectional study including 22556 adult Chinese individuals suggested HUA was independently associated with hypertension in male subjects under 60 years.37 Cohort studies and nested case-control studies found that HUA may modestly increased the risk of incident hypertension.38 Animal model showed that both increased blood pressure and HUA could be induced by providing a uricase inhibitor (oxonic acid) in the diet.39 Moreover, HUA has been found to be associated with unfavorable prognosis in patients with hypertension, including cardiovascular diseases, all-cause mortality and diabetes.40 Several factor may account for the association between hypertension and HUA. Kidney associated decreased excretion of uric acid may cause elevated serum uric acid.41 Moreover, oral administration of diuretics for treating hypertension have been found to suppresses serum uric acid secretion. 42
Consistent with the a study in children and adolescents with autism spectrum disorder,20 the present study suggested that the prevalence of HUA increased with BMI. In the general population, a study with 10611 patients with hypertension fund that higher BMI was significantly and independently associated with new-onset HUA.43 The interaction of BMI and ABCG2 rs2231142 variant could markedly increased the risk of HUA.44 In addition, BMI could modify uric acid levels by sex and genetic variants within SLC2A9.45 It was suggested that insulin resistance induced by accumulation of fat is the underlying mechanism between obesity and HUA.46 In China, a multicentre cross‑sectional study reported that the prevalence of obesity among inpatients with schizophrenia was 1.48 times higher than that in the gender- and age- matched healthy controls.47 The prevalence of obesity and overweight in patients with schizophrenia was 16.3% and 29.5%, respectively.47 Screening and intervention for obesity may contribute to decrease the prevalence of HUA in patients with schizophrenia.
The present study showed that TC, TG and LDL were significantly associated with increased risk for HUA in patients with schizophrenia, which was consistent with studies in the general population. A prospective cohort study found the level of TC and TG could predict the risk of HUA.48 In patients with chronic kidney disease, hyperlipidemia is an independent risk factor for HUA.49 Su et al. reported that an increase of 1 mg/dL in serum uric acid was related to a 2.438 mg/dL increase in cholesterol (P<0.05), a 10.358 mg/dL increase in triglyceride (P<0.001) in male subjects, and an increase of 1 mg/dL serum uric acid was related to a 3.708 mg/dL increase in triglyceride (P<0.01) in female subjects.50 The synthesis of triglycerides needs NADPH, which results in elevated uric acid production, this may partly explain the relation between triglycerides and HUA.51 A longitudinal observational study in China found that 18.36% of 62533 patients with schizophrenia had dyslipidemia, and the prevalence of dyslipidemia in mental disorder inpatients increased nearly 3 times between 2005 and 2018.52 Thus, more attention should be paid to the risk of HUA in schizophrenia patients with dyslipidemia.
There were several limitations in the present study. First, this study was a retrospective cross-sectional study. We could not prove a direct causal relationship between HUA and these associated risk factors in our study. In addition, We could not assess other associated risk factors of HUA, such as smoking, antipsychotics, history of HUA, dietary habit, and health behaviors. Second, we only included inpatients from a public psychiatric hospital, patients with schizophrenia in general hospitals and communities were nor enrolled in this study. However, given on the large sample, the results of this study could partly reflect the prevalence of HUA in patients with schizophrenia in China. Third, we did not enroll healthy controls in this study. Thus, some bias possibly occurred when comparing our findings with the studies in the general population .