Silent Inflammation: A Critical Narrative Review of the Relationship Between Periodontal Disease and Psychosis-The Role of Oxidative Stress and Iatrogenic Comorbidities.

Extensive epidemiological evidence links psychosis (PZ)-particularly schizophrenia (SCZ)-with disproportionate periodontal destruction, suggesting shared biological vulnerability. Beyond local tissue damage, periodontitis provides a clinically accessible translational paradigm for systemic redox dysregulation, where sustained inflammatory activation coincides with measurable oxidative injury and exhaustion of antioxidant (AO) defenses across cardiometabolic and neuropsychiatric domains. In this critical narrative review, we argue that the excess periodontal burden in PZ reflects a "pathological confluence" shaped by antipsychotic-associated iatrogenic factors, rapid metabolic deterioration, and chronic oxidative distress. We appraise the thioredoxin-interacting protein (TXNIP)-NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) axis as a metabolic-redox sensor linking dysglycemia to periodontal inflammasome activation and downstream cytokine signaling, and address the advanced glycation end-products (AGEs)-receptor for advanced glycation end-products (RAGE) axis as a key immunometabolic redox pathway. We further discuss mitochondrial dysfunction, impaired mitophagy, and mitochondrial deoxyribonucleic acid (mtDNA) leakage as damage-associated molecular patterns (DAMPs) that can amplify systemic "silent inflammation". Integrating evidence on periodontal pathogen-host interactions and redox-sensitive neuroimmune pathways (including NADPH oxidase 4 (NOX4)-linked microglial activation), we propose periodontitis as a plausible upstream amplifier that may exacerbate vascular dysfunction and compromise blood-brain barrier (BBB) integrity. Finally, we outline clinically measurable biomarker readouts to operationalize redox-informed integrated care and highlight the need for pragmatic trials targeting clinically meaningful endpoints to improve somatic longevity in PZ-spectrum populations. We acknowledge that current human evidence is largely associative and that the proposed mechanistic links remain hypothesis generating.