Abstract
The prolonged usage of atypical antipsychotic drugs (AAPD) among individuals with schizophrenia often leads to metabolic side effects such as dyslipidemia. These effects not only limit one's selection of AAPD but also significantly reduce compliance and quality of life of patients. Recent studies suggest that bilirubin plays a crucial role in maintaining lipid homeostasis and may be a potential pre-treatment biomarker for individuals with dyslipidemia. The present study included 644 schizophrenia patients from two centers. Demographic and clinical characteristics were collected at baseline and 4 weeks after admission to investigate the correlation between metabolites, episodes, usage of AAPDs, and occurrence of dyslipidemia. Besides, we explored the combined predictive value of genotypes and baseline bilirubin for dyslipidemia by employing multiple PCR targeted capture techniques to sequence two pathways: bilirubin metabolism-related genes and lipid metabolism-related genes. Our results indicated that there existed a negative correlation between the changes in bilirubin levels and triglyceride (TG) levels in patients with schizophrenia. Among three types of bilirubin, direct bilirubin in the baseline (DBIL-bl) proved to be the most effective in predicting dyslipidemia in the ROC analysis (AUC = 0.627, p < 0.001). Furthermore, the odds ratio from multinomial logistic regression analysis showed that UGT1A1*6 was a protective factor for dyslipidemia (ß = -12.868, p < 0.001). The combination of baseline DBIL and UGT1A1*6 significantly improved the performance in predicting dyslipidemia (AUC = 0.939, p < 0.001). Schizophrenia patients with UGT1A1*6 mutation and a certain level of baseline bilirubin may be more resistant to dyslipidemia and have more selections for AAPD than other patients.