Reduced serum paraoxonase 1 (PON1) activity in patients with schizophrenia treated with olanzapine but not quetiapine

Cüneyt Ünsal,¹ Yakup Albayrak,¹ Neslihan Albayrak,² Murat Kuloğlu,³ Kenji Hashimoto<sup>4

1</sup>Department of Psychiatry, Namik Kemal University School of Medicine, Tekirdag, Turkey; ²Department of Cardiology, Kirklareli State Hospital, Kirklareli, Turkey; ³Department of Psychiatry, Akdeniz University School of Medicine, Antalya, Turkey; ⁴Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan

Background: Second generation antipsychotics (SGAs) are currently the most prescribed drugs in the treatment of schizophrenia. Despite their advantages, which include greater improvement in negative symptoms, cognitive function, prevention of deterioration, quality of life, and fewer extrapyramidal symptoms, the concern regarding metabolic abnormalities which might cause cardiovascular diseases during treatment with SGAs have been rising. Paraoxonase 1 (PON1) is an enzyme mostly located on high-density lipoprotein particles, and has been shown to protect or inhibit lipoprotein oxidation. Growing evidence suggests that PON1 plays a key role in the pathophysiology of atherosclerosis.
Methods: In the present study, we measured serum PON1 activity and serum levels of total cholesterol (TC), triglyceride, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in patients with schizophrenia, who had been treated with either olanzapine or quetiapine, and in healthy controls. Thirty five patients who had been treated with olanzapine, 29 patients who had been treated with quetiapine, and 32 age, sex, and smoking status-matched healthy control (HC) participants were enrolled. Serum PON1 activity and serum levels of TC, triglyceride, HDL-C, and LDL-C were measured.
Results: Serum PON1 activity in the olanzapine group was significantly lower than that of HC and quetiapine groups. Furthermore, serum levels of TC and LDL-C in the olanzapine group were significantly higher than those of quetiapine and HC groups. Interestingly, there was a positive correlation between PON1 activity and HDL-C levels in the olanzapine group.
Conclusion: These findings suggest that serum PON1 activity in patients treated with olanzapine was lower than that of HC and quetiapine groups, and that PON1 may play a role in the metabolic side effects associated with olanzapine treatment. A further study to examine the relationship between serum PON1 activity and cardiovascular and metabolic side effects during treatment with SGAs will be of great interest.

Keywords: second generation antipsychotics, SGA, atherosclerosis, metabolic, dyslipidemia, LDL-C