Influence of antipsychotic medications on hyperlipidemia risk in patients with schizophrenia: evidence from a population-based cohort study and in vitro hepatic lipid homeostasis gene expression

Tien-Yuan Wu; Ni Tien; Cheng-Li Lin; Yu-Cun Cheah; Chung Y Hsu; Fuu-Jen Tsai; Yi-Jen Fang; Yun-Ping Lim

doi:10.3389/fmed.2023.1137977

Influence of antipsychotic medications on hyperlipidemia risk in patients with schizophrenia: evidence from a population-based cohort study and in vitro hepatic lipid homeostasis gene expression

Front Med (Lausanne). 2023 Jun 22:10:1137977. doi: 10.3389/fmed.2023.1137977. eCollection 2023.

Authors

Tien-Yuan Wu^{1

2}, Ni Tien^{3

4}, Cheng-Li Lin⁵, Yu-Cun Cheah⁶, Chung Y Hsu⁷, Fuu-Jen Tsai^{8

9

10

11}, Yi-Jen Fang^{12

13

14

15

16}, Yun-Ping Lim^{6

9

17}

Affiliations

¹ Graduate Institute of Clinical Pharmacy, College of Medicine, Tzu Chi University, Hualien, Taiwan.
² Department of Pharmacy, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan.
³ Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan.
⁴ Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan.
⁵ Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan.
⁶ Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan.
⁷ Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
⁸ School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
⁹ Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
¹⁰ Division of Medical Genetics, China Medical University Children's Hospital, Taichung, Taiwan.
¹¹ Department of Biotechnology and Bioinformatics, Asia University, Taichung, Taiwan.
¹² Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
¹³ Ph.D. Program in Environmental and Occupational Medicine, College of Medicine, Kaohsiung Medical University and National Health Research Institutes, Kaohsiung, Taiwan.
¹⁴ Department of Environmental Health, Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
¹⁵ Department of Post-Baccalaureate Medicine, College of Medicine, National Chung-Hsing University, Taichung, Taiwan.
¹⁶ Digestive Disease Center, Show Chwan Memorial Hospital, Changhua, Taiwan.
¹⁷ Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.

Abstract

Introduction: Schizophrenia increases the risk of mortality and cardiovascular disease (CVD) risk. However, the correlation between antipsychotics (APs) and CVD remains controversial. Hyperlipidemia is a significant risk factor for CVD.

Methods: We conducted a nationwide population-based retrospective cohort study to investigate the effects of APs on the risk of hyperlipidemia and lipid homeostasis gene expression. We used data from the Longitudinal Health Insurance Database of Taiwan on new-onset schizophrenia patients and a comparison cohort without schizophrenia. We used a Cox proportional hazards regression model to analyze the differences in hyperlipidemia development between the two cohorts. Furthermore, we examined the effects of APs on the hepatic expression of lipid homeostasis-related genes.

Results: After adjusting for potential interrelated confounding factors, the case group (N = 4,533) was found to have a higher hyperlipidemia risk than the control cohort (N = 4,533) [adjusted hazard ratio (aHR), 1.30, p < 0.001]. Patients with schizophrenia without APs had a significantly higher risk of hyperlipidemia (aHR, 2.16; p < 0.001). However, patients receiving APs had a significantly lower risk of hyperlipidemia than patients not receiving APs (all aHR ≤ 0.42, p < 0.001). First-generation antipsychotics (FGAs) induce the expression of hepatic lipid catabolism genes in an in vitro model.

Discussion: Patients with schizophrenia had a higher risk of hyperlipidemia than controls; however, compared with non-treated patients, AP users had a lower risk of hyperlipidemia. Early diagnosis and management of hyperlipidemia may help prevent CVD.

Keywords: antipsychotic medications; cohort study; hyperlipidemia; lipid homeostasis; schizophrenia.