Mind over microglia: using mindfulness-based interventions to target stress-induced neuroinflammatory mediators to improve behavioral symptoms

Abstract Chronic psychosocial stress is associated with dysregulation of neuroendocrine and immune pathways that may contribute to symptom exacerbation in individuals with psychotic disorders. Repeated activation of the hypothalamic–pituitary–adrenal (HPA) axis and sympathetic systems can alter glucocorticoid signaling, inflammatory mediators, blood–brain barrier function, and neuroimmune communication. Evidence implicates stress-responsive inflammatory pathways and heterogeneous microglial states in neural circuits involved in cognition, emotional regulation, and stress responsivity. Psychotic disorders are multifactorial and biologically heterogeneous, and neuroinflammatory abnormalities are unlikely to represent a uniform mechanism across schizophrenia or bipolar disorder. Stress-related immune dysregulation may instead be particularly relevant to subgroups defined by inflammatory status, disease stage, medication exposure, and metabolic factors. Mindfulness-based interventions (MBIs) have been associated with reduced perceived stress and alterations in HPA-axis activity, inflammatory biomarkers, neurotrophic factors, and stress-responsive neural circuitry. Mindfulness-based approaches may also improve clinical outcomes in schizophrenia-spectrum disorders, although findings remain heterogeneous and mechanistic studies in psychotic populations are limited. Direct evidence that MBIs modify microglial phenotype or activation state in psychotic disorders is lacking; proposed effects on neuroimmune function therefore remain inferential, supported primarily by peripheral biomarkers, neuroendocrine findings, and evidence from nonpsychotic and preclinical populations. This review evaluates evidence linking chronic stress and neuroendocrine and immune dysregulation with psychotic symptom expression, distinguishes established associations from proposed mechanisms, and considers the potential role of disease-adapted MBIs as adjunctive interventions.