Potential risk factors of susceptibility to recurrent depression

• Published in: Brain research bulletin Vol. 227; p. 111374
• Main Authors: Wang, Shuzhuo, Guo, Lei, Wang, Chuang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2025; Elsevier
• Subjects: Adult; Animals; BICC1; Depression - metabolism; Depressive Disorder, Major - blood; Depressive Disorder, Major - metabolism; Disease Models, Animal; Disease Susceptibility; Female; HIF1α; HSP90; HSP90 Heat-Shock Proteins - blood; HSP90 Heat-Shock Proteins - metabolism; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - blood; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Major depressive disorder (MDD); Male; Mice; Mice, Inbred C57BL; Middle Aged; Prefrontal Cortex - metabolism; Recurrence; Recurrent depression; Risk Factors; Stress, Psychological - metabolism; HSP90; HIF1α; Recurrent depression; BICC1; Major depressive disorder (MDD)
• ISSN: 0361-9230; 1873-2747; 1873-2747
• DOI: 10.1016/j.brainresbull.2025.111374

Major depressive disorder (MDD) is a highly prevalent and recurrent neuropsychiatric disorder associated with alterations in the BicC family RNA binding protein 1 (BICC1). However, the potential risk factors that regulate BICC1 and affect susceptibility to recurrent depression remain unclear. Herein, we firstly tested the heat shock protein 90 (HSP90), hypoxia-inducible factor 1-alpha (HIF1α), and BICC1 in the serum of the patients that were in first-episode or recurrent depression, as well as their controls. Then, through re-exposure to chronic unpredictable mild stress (CUMS) in mice, an animal model of recurrent depression was assessed. And the expression of HSP90, HIF1α, and BICC1 in the prefrontal cortex (PFC) were analyzed. We found that HSP90, HIF1α, and BICC1 were significantly increased in the serum of depressed patients, especially in those with recurrent depression, indicating that these molecules may serve as specific pathogenetic risk factors for depression, especially depression recurrence. In addition, the recurrent depression mice model was found to be accompanied by a significant increase in expression of HSP90, HIF1α and BICC1 in the PFC. The current study identified HSP90, HIF1α, and BICC1 as novel potential risk factors that affect susceptibility to recurrent depression. •We identify HSP90, HIF1α, and BICC1 as circulating biomarkers associated with recurrent depression.•We developed a mouse model for depression relapse and validated related molecular changes.•These molecules may serve as novel therapeutic targets for preventing or mitigating depression recurrence.