The relationship between the serum bilirubin levels and metabolic syndrome in schizophrenia patients

Objective: Especially with the use of atypical antipsychotics, the increase of the metabolic side effects constitutes a major problem in schizophrenia patients. Serum bilirubin levels have been reported to be associated with insulin resistance, abdominal obesity, and metabolic syndrome (MS) (1,2). However, the relationship between MS parameters and bilirubin levels has not been investigated in schizophrenia patients. It has been reported that antipsychotic drugs do not cause significant changes in serum bilirubin levels (3). The objective of this study was to investigate the association between bilirubin levels and the parameters associated with MS in schizophrenia patients.

Methods: Ninety one schizophrenic patients (38 female, 53 male) receiving antipsychotics for at least one year were included in the study. The parameters associated with MS were as follows: Body mass index, body weight, waist circumference, systolic and diastolic blood pressure, fasting blood glucose, insulin, serum triglycerides, HDL cholesterol levels, and the insulin resistance as calculated by using the value HOMA (homeostasis model assessment). The criteria were based on ATP-III criteria for metabolic syndrome (Adult Treatment Panel III). Statistical analysis was performed by using SPSS 17.0 (for Windows).

Results: Serum triglyceride levels were inversely correlated with serum direct bilirubin (p=.006) and positively correlated with indirect/direct bilirubin ratio (p =. 002). Serum HDL levels (p=.018) showed a significant positive correlation with indirect/direct bilirubin ratio. Waist circumference (p=.048) showed a significant negative correlation with serum total bilirubin. The levels of insulin (p =.038) and value of HOMA (p =.015) were inversely correlated with serum direct bilirubin. The rate of metabolic syndrome was significantly lower in the patients with highest quartile (75-100) of the serum direct bilirubin levels than the other quartiles (p=.022). In these patients, the ratio of the patients that meet criteria for metabolic syndrome according to levels of the fasting triglyceride (p=.013) and HDL (p=.040) was significantly lower than others. Additionally, the means of body weight (p=.026), waist circumference (p=.022), and serum triglyceride levels (p=.039) of these patients were found significantly lower.

Conclusions: In this study we found that bilirubin levels are associated with metabolic syndrome and its parameters and high levels of serum direct bilirubin may be associated with the lower risk for MS in schizophrenia patients; similar to the healthy individuals (1,2,4). Our study is the first study investigating this issue. Our results may be important for the following aspects: High serum direct bilirubin levels may serve as an easily applicable, inexpensive marker indicating lower MS risk for schizophrenic patients. Additionally, it may be possible to prevent antipsychotics induced metabolic side effects by avoiding the drugs with higher risk for MS, in the patients with low levels of direct bilirubin. Due to the relatively limited number of patients and cross-sectional nature, our results required to be confirmed by longitidunal studies with larger samples.