Periodontitis and Neuropsychiatric Disorders: Epidemiological and Mechanistic Evidence

This review aims to critically analyze the epidemiological evidence and mechanistic insights linking periodontitis with the onset, progression, or severity of neuropsychiatric disorders. From an epidemiological perspective, eligible evidence was identified regarding disorders related to trauma, stress, anxiety, depressive, and bipolar disorders, whereas no studies meeting the predefined inclusion criteria were found for the remaining considered disorders. The strongest epidemiological evidence was observed for depressive disorders and anxiety- and stress-related conditions. However, the predominance of cross-sectional studies, together with substantial methodological heterogeneity, limits conclusions regarding temporality and causality. From a mechanistic perspective, the available evidence regarding the association between periodontitis and neuropsychiatric disorders predominantly supports as mechanisms (1) microbial pathways (microbial translocation and functional dysregulation of the oral microbiome), (2) inflammatory and immune pathways (systemic (meta)inflammation and trafficking of immune players systemic), and (3) shared underlying vulnerabilities (behavioral factors, medication-related effects, lifestyle and systemic health factors, and genetic mechanisms). Periodontitis may promote a persistent low-grade systemic inflammatory state through the release of bacterial products and inflammatory mediators into the circulation, thereby influencing immune, neuroendocrine, and vascular pathways relevant to neuropsychiatric vulnerability. Moreover, the hematogenous dissemination or swallowing of periodontal bacteria and their virulence factors may contribute to microbial remodeling at distant sites, including the gut, supporting the concept of an oral-gut-brain axis. Overall, the evidence analyzed supports periodontitis as a potential modifiable contributor within a broader biopsychosocial network linking oral and mental health, while highlighting the need for longitudinal studies and interventional trials to clarify causality and clinical relevance.