ArticleFrontiers in psychiatry2026
Associations between serum tumor necrosis factor-alpha, hippocampal-prefrontal-ventricular volumes, and clinical profiles in schizophrenia: a biomarker and neuroimaging study in North Sumatera, Indonesia.
Article in Frontiers in psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Schizophrenia is a neurodevelopmental disorder with systemic inflammation that is thought to play a role in its pathophysiology. The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) has been reported to be dysregulated in individuals with schizophrenia, but its relationship with brain volume changes remains inconsistent. This study aimed to analyze differences in TNF-α levels and brain volume (hippocampus, prefrontal cortex, and lateral ventricles) and their correlations in schizophrenia patients compared to healthy controls. Methods: This analytical cross-sectional investigation was conducted on 50 schizophrenia patients and 50 healthy Batak controls at the Prof. M. Ildrem Provincial Mental Hospital, Medan. Serum TNF-α levels were measured by ELISA, while brain structure volume was measured by 1.5 T MRI and analyzed using AnalyzePro software. Results: TNF-α levels in the schizophrenia group were significantly lower (3.35 pg/dl) than in the control group (16.90 pg/dl). No significant differences in hippocampal and prefrontal cortex volume were found between the groups. However, lateral ventricle volume was significantly larger in schizophrenia. Correlation analysis showed a weak negative relationship between TNF-α and prefrontal cortex volume only in the schizophrenia group. Discussion: The finding of low TNF-α in schizophrenia supports the complexity of immune dysfunction in schizophrenia, which may be influenced by medication or disease phase. Consistent ventricular enlargement reinforces previous neuroanatomical findings. The association of TNF-α with the prefrontal cortex only within the schizophrenia cohort indicates a specific interaction between inflammation and brain morphology in this patient population. Conclusions: The findings support TNF-α dysregulation in schizophrenia, albeit at lower levels. Lateral ventricular enlargement was consistently found, while changes in hippocampal and prefrontal cortex volume may be more subtle in this population. The negative correlation between TNF-α and the prefrontal cortex in schizophrenia suggests a potential role for inflammation in the pathology of this brain region.
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