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Updated: Oct 8, 2026
Individualized rTMS Treatment for Depression using an fMRI-Based Targeting Method
Published on: August 2, 2021
Functional involvement of HMGB1-related neuroinflammation in depression and its modulation by intermittent
Yaxing Zhang1, Shiyu Xin1, Kaiming Zhang1
1Department of Psychiatry, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050031, People's Republic of China; The Mental Health Center of Hebei Medical University, Shijiazhuang, Hebei, 050031, People's Republic of China; The Mental Health Institute of Hebei Medical University, Shijiazhuang, Hebei, 050031, People's Republic of China.
Purpose:
Intermittent theta-burst stimulation (iTBS) is widely used for its rapid antidepressant efficacy in clinical practice. However, its underlying neuroimmune mechanisms and objective biomarkers of treatment response remain largely unexplored. High mobility group box 1 (HMGB1), a critical driver of neuroimmune interactions in stress-related disorders, may link peripheral inflammation to central pathological processes in depression and may serve as a potential therapeutic target. Therefore, we aimed to explore the functional involvement of HMGB1 in depression and whether HMGB1-related inflammatory signaling is modulated by iTBS.
Methods:
We measured circulating HMGB1 levels in patients with Major depressive disorder (MDD). In mice exposed to chronic restraint stress (CRS) or LPS, HMGB1/TLR4/NF-κB signaling and neuroinflammatory responses in the prefrontal cortex were assessed. Glycyrrhizic acid (GA), a well-established HMGB1 antagonist, was used to determine the functional relevance of HMGB1. iTBS-mediated antidepressant effects were assessed via behavioral tests and HMGB1-related inflammatory signaling analysis.
Results:
HMGB1 was markedly upregulated in patients and in depressive‑like mouse models, accompanied by activation of the HMGB1/TLR4/NF-κB signaling pathway and increased neuroinflammation. GA alleviated depressive-like behaviors. iTBS reversed behavioral deficits and suppressed HMGB1-associated inflammatory signaling.
Conclusion:
HMGB1 is functionally involved in depression, and the therapeutic effects of iTBS are associated with suppression of HMGB1-related neuroinflammatory signaling. These findings suggest that HMGB1 may have potential as a biomarker for monitoring the biological effects of iTBS and may provide a basis for further investigation of HMGB1 in treatment response.
