The relationship between components of metabolic syndrome and disease onset in patients with schizophrenia

The increased prevalence of metabolic syndrome and some of its components among patients with schizophrenia may be related to a shared genetic liability (Malan-Müller et al., 2016). Metabolic abnormalities in schizophrenia may therefore be associated with the more severe forms of illness and an earlier onset (Saari et al., 2004). Only one study has previously investigated possible associations between schizophrenia onset and plasma triglyceride concentration (Saari et al., 2004), and there are no reports comparing variations in other components of metabolic syndrome and disease onset. We investigated the associations between plasma glucose and lipid concentrations, body mass index (BMI) values, and age of disease onset among Croatian patients with schizophrenia. Two hundred and forty five patients (males/females: 131/114), aged 41.8 ± 11.9 years, meeting the DSM-IV criteria for schizophrenia and under a stable antipsychotic medication regimen for at least 12 months were included in this study. The study was approved by the Ethics Committee of the School of Medicine, University of Rijeka, Croatia and written informed consent was obtained from all patients. Age at onset was classified as early (≤ 26 years) or late (> 26 years), based on the median age for the entire sample at the first hospital admission due to a psychotic episode which included the diagnosis of schizophrenia. The mean age at first hospital admission was not significantly different between male and female patients (26.2 7.6 vs. 27.6 8.2, P > 0.05). Fasting plasma total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride, and glucose levels were determined with an autoanalyzer (Olympus AU640, Olympus, Tokyo, Japan), BMI was calculated (BMI = weight in kg/square of height in meter), and the associations between lipid and glucose concentrations and BMI values and age at onset were determined by multiple regression analysis adjusted for age and illness duration. A Mann-Whitney U test was used to test for differences between mean plasma lipid and glucose concentrations and BMI values as a function of disease onset. Males and females were analyzed separately to account for a possible interaction between the metabolic parameters and gender (Pradhan, 2014 ; Varlamov et al., 2015). All statistical analyses were conducted with Statistica for Windows, version 9 (StatSoft, Inc., Tulsa, OK, USA), and P values less than 0.05 (P 0.05). Significant associations between plasma triglyceride and glucose levels and age at first hospitalization were observed for male patients only ( = -0.35, F = 7.51, P = 0.008 and = 0.29, F = 9.23, P = 0.003). Triglyceride levels were specifically higher in males with early (N = 79), compared to late onset (N = 52, 2.5 ± 1.4 vs. 1.7 ± 0.8, z = - 2.01, P = 0.042), while glucose levels were higher in males with late compared to early onset (5.9 ± 1.4 vs. 5.3 ± 0.7, z = - 2.59, P = 0.009) (Table 1). The age at first hospitalization accounted for approximately 12% of the variability in triglyceride levels and 8% of the variability in glucose levels (R2 change = 0.122 and 0.082, respectively). These results suggest statistically significant although relatively weak associations between age of schizophrenia onset and several components of metabolic syndrome, in male patients only. Earlier disease onset was associated with higher plasma triglyceride values, in alignment with a previous report of higher serum triglyceride levels in patients with early-onset schizophrenia (Saari et al., 2004). However, higher plasma glucose levels were observed in males with late onset schizophrenia, which is inconsistent with our hypothesis that individuals with an earlier disease onset are more vulnerable to the development of diabetes. Higher glucose levels may be present before the development of overt psychotic symptoms and could delay the onset of psychosis by influencing dopaminergic neurotransmission. Male rats treated with a dopamine antagonist manifest higher glucose and insulin levels, and dopamine D2 receptor knockout mice develop glucose intolerance and an impaired insulin response to glucose (Baptista et al., 2002 ; García-Tornadú et al., 2010). One recent study also found a lower severity of positive symptoms of schizophrenia (associated with dopamine system hyperactivity) in first-episode patients manifesting with higher plasma glucose levels (Zhang et al., 2015). Additional studies are needed to elucidate this relationship