In addition to established systemic contributors to periodontal and peri-implant diseases, other factors, such as chronic stress and depression, may influence disease initiation, progression, and treatment outcomes. This review examines the neurobiological and neurobehavioral pathways linking chronic stress and depression with periodontitis and peri-implantitis—associations that have been minimally explored and primarily investigated in necrotizing periodontal disease—alongside their potential interactions with the periodontal immune–microbiome equilibrium. Emerging evidence indicates that disruptions in neurobiological and neurobehavioral mechanisms, together with immune–microbiome imbalances associated with chronic stress and depression, may synergistically contribute to the development and exacerbation of not only necrotizing periodontal lesions but also chronic periodontitis and peri-implantitis. These interactions could be particularly significant in recurrent or aggressive forms of periodontal and peri-implant disease that often resist conventional therapies, suggesting that, if confirmed, they may inform personalized prevention and treatment strategies that address immune–microbiome dysregulation, neurobehavioral factors, and neurobiological mechanisms, especially in patients experiencing chronic stress and depression.
