Depressive disorder is a common disease characterized by depressed mood and loss of pleasure, which often brings a great grief to patients and a huge burden to the society. Currently, the therapeutic strategy has made a rapid progress, but even the most well-studied and commonly used antidepressants will take weeks to produce a desired effect and have some side-effects. Besides, the objective and specific diagnostic indexes are still absent. Many important hypotheses have been proposed and inflammation is one of them. Among the inflammatory cytokines that might be closely related to depression, HMGB1 is a novel and vital one.

We reviewed and analyzed literature on PubMed and web of science using the relevant key words ( "depression/MDD" in conjunction with "HMGB1/high mobility group box 1).

We found that both clinical and laboratory studies demonstrated pro-inflammatory role of HMGB1 in depressive disorder, while conditional knockout or inhibition of HMGB1 could alleviate inflammation and depression.

Therefore, in this review we will talk about the possible role of HMGB1 in the development of depressive disorder and the underlying mechanisms with the hope of providing evidence for a novel and effective therapy for depressive disorder.