Progress in research on the inflammatory and immunological mechanisms and interventions for the comorbidity of psoriasis and depression

Psoriasis is a chronic systemic inflammatory disease centered on the IL-23/Th17 axis, encompassing two major clinical phenotypes: Cutaneous psoriasis and psoriatic arthritis (PsA).Depressive disorders are among the most common psychiatric comorbidities in patients with psoriasis; a bidirectional association exists between the two, creating a vicious cycle in which each condition exacerbates the other.Current evidence suggests that chronic systemic inflammation and immune dysregulation may serve as the central biological bridge linking the two diseases.While direct clinical data from psoriasis and PsA populations confirm this bidirectional association, the causal chain from peripheral inflammation to central depressive symptoms has not been fully validated in comorbid conditions.At the mechanistic level, cytokines such as IL-17A, TNF-α, and IL-6-produced by the activation of the IL-23/Th17 axis-enter the circulation and reach the central nervous system via the blood-brain barrier, the choroid plexus, and the vagus nerve pathway, where they activate microglia and disrupt monoaminergic neurotransmission; the peripheral corticotropin-releasing hormone (CRH)-mast cell-IL-17 loop of the hypothalamic-pituitary-adrenal axis and the central CRH-cortisol-glucocorticoid resistance loop reinforce each other; indoleamine 2,3dioxygenase-mediated metabolic shifts in the kynurenine pathway convert peripheral inflammation into serotonin depletion and neurotoxic damage; central sensitization in chronic pain and impaired brain derived neurotrophic factor signaling further exacerbate dysfunction in emotional regulation circuits; gut dysbiosis, through shortchain fatty acid deficiency and intestinal barrier damage, may contribute to systemic inflammation.In terms of interventions, clinical data from patient-reported symptom scales indicate that biologics, small-molecule drugs, antidepressants, psychobehavioral interventions, and lifestyle modifications have all shown potential for improving depressive symptom scores; however, high-quality evidence with clinically diagnosed depressive disorders as the primary outcome remains lacking.Future research should 4 / 63 include mechanism-driven prospective cohort studies and randomized controlled trials with clinically diagnosed depressive disorders as a pre-specified endpoint to advance the integrated management of dermatological-psychiatric comorbidity.