Work

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

Year: 2026

Type: article

Abstract: Background 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. Methods 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. Results 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. Conclusion 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.

Source: Frontiers in Psychiatry

DOI: 10.3389/fpsyt.2026.1715991