Sci Adv. 2025 Jul 25;11(30):eadx3698. doi: 10.1126/sciadv.adx3698. Epub 2025 Jul 25.
ABSTRACT
The incidence rate, disability rate, and suicide rate of major depressive disorder (MDD) are increasing year by year, but the mechanism has not yet been clarified. There are multiple hypotheses about the etiology of MDD, among which the cross-talk between the immune system and the nervous system breaks the boundaries between neurologic and psychiatric disorders and provides a breakthrough in the etiologic study of MDD. Combining the immunological “danger theory,” inflammation triggered by damage-associated molecular patterns (DAMPs) produced by the central nervous system (CNS) and the immune system may be the underlying cause of MDD; however, MDD has not yet been explored in depth from this perspective. This work reviewed the cross-talk of DAMPs between the CNS and the immune system, suggesting that stress-induced CNS inflammation is an important pathogenetic mechanism of MDD, and the cross-talk of DAMPs is a central factor, refining the hypothesis of the etiology of MDD.
PMID:40712012 | DOI:10.1126/sciadv.adx3698
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