# Comparing metabolic syndrome parameters, oxidative stress, cellular metabolism, and gene polymorphism between people with schizophrenia and healthy controls

## TL;DR

People with schizophrenia show altered glutathione levels and metabolic risk factors, possibly due to genetic variations in the GCLC gene.

## Contribution

This study identifies early metabolic and oxidative stress changes in schizophrenia linked to GCLC gene polymorphisms.

## Key findings

- Individuals with schizophrenia had lower GSH and GSSG levels but a higher GSH/GSSG ratio compared to controls.
- High-risk GCLC genotypes were associated with higher MDA levels in schizophrenia patients.
- GSSG levels in schizophrenia correlated negatively with LDL-c, while MDA correlated with diastolic blood pressure in controls.

## Abstract

Patients with schizophrenia have an increased risk of metabolic syndrome and cardiovascular disease, even in the absence of antipsychotic treatment. Oxidative stress, mitochondrial dysfunction, and genetic polymorphisms of the GCLC gene may contribute to this vulnerability.

We conducted an analytical observational case–control study including 25 patients with schizophrenia (drug-naïve or drug-free) and 25 age- and sex-matched healthy controls, both groups predominantly men, recruited from two Indonesian psychiatric hospitals (2021–2023). Anthropometric (waist circumference, BMI, and blood pressure), metabolic (LDL-c, HDL-c, triglyceride, and HbA1c), and oxidative stress parameters (malondialdehyde [MDA], reduced glutathione [GSH], oxidized glutathione [GSSG], manganese superoxide dismutase [MnSOD], and adenosine triphosphate [ATP]) were measured from the blood sample. GCLC GAG trinucleotide repeat polymorphisms were analyzed by PCR.

Individuals with schizophrenia had significantly lower GSH and GSSG levels than controls but a higher GSH/GSSG ratio. Plasma MDA levels were lower in schizophrenia. High-risk GCLC genotypes were associated with higher MDA levels in schizophrenia. In the schizophrenia group, GSSG showed a moderate negative correlation with LDL-c (r = −0.430, p = 0.032). In the control group, MDA correlated positively with diastolic blood pressure (r = 0.411, p = 0.041) and GSSG correlated positively with triglycerides (r = 0.495, p = 0.012). No significant differences in ATP levels or mitochondrial activity were observed.

Schizophrenia is associated with disruption of the glutathione system and early metabolic risk, influenced in part by GCLC GAG polymorphisms. These findings support the importance of early metabolic screening in schizophrenia.