HMGB1 involved in stress-induced depression and its neuroinflammatory priming role: a systematic review

Evidence from clinical and preclinical studies has demonstrated that stress can cause depressive-like symptoms including anhedonia and psychomotor retardation, namely, the manifestation of motivational deficits in depression. The proximate mediator of linking social-environmental stress with internal motivational deficits remains elusive, although substantial studies proposed neural endocrine mechanisms. As an endogenous danger-associated molecule, high mobility group box-1 (HMGB1) is necessary and sufficient for stress-induced sensitization of innate immune cells and subsequent (neuro)inflammation.

This review aims to provide evidence to unveil the potential mechanism of the relationship between motivational deficits and stress in depression.

We reviewed original case-control studies investigating the association between HMGB1-mediated inflammation and stress-induced depression. The literature search of Pubmed and Web of Science electronic database from inception up to March 28th, 2019 were conducted by two independent authors. We performed a qualitative systematic review approach to explore the correlation between HMGB1-mediated inflammation and anhedonia/psychomotor retardation in depression.

A total of 69 studies based on search strategy were retrieved and seven eligible studies met the inclusion criteria. Studies showed that HMGB1 was implicated with depressive-like behaviors, which are similar with motivational deficits. Furthermore, HMGB1-mediated inflammation in depressive-like behaviors may be involved in Nod-like receptor family pyrin domain containing three (NLRP3) inflammasome and proinflammatory cytokines, abnormal kynurenine pathway and imbalance between neuroprotective and neurotoxic factors.

We found that stress-induced inflammation mediated by HMGB1 may affect motivational deficits through regulating dopamine pathway in corticostriatal neurocircuitry. The systematic review may shed light on the novel neurobiological underpinning for treatment of motivation deficits in depression.