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Epigenetic regulation of circadian clock genes in depression: multidimensional mechanisms and translational precision therapeutics
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Jia-cheng DAI1, Man-shu ZOU1, 3, Hai-xia HE2, Yu-hong WANG1, 3, *
Acta Pharmaceutica Sinica | 2025, 60(12) : 3665 - 3681
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Acta Pharmaceutica Sinica | 2025, 60(12): 3665-3681
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Epigenetic regulation of circadian clock genes in depression: multidimensional mechanisms and translational precision therapeutics
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Jia-cheng DAI1, Man-shu ZOU1, 3, Hai-xia HE2, Yu-hong WANG1, 3, *
Affiliations
  • 1Academy of Chinese Medical Sciences, Hunan University of Traditional Chinese Medicine, Changsha 410208, China
  • 2First Affiliated Hospital, Hunan University of Traditional Chinese Medicine, Changsha 410007, China
  • 3Hunan Key Laboratory of Traditional Chinese Medicine Prevention and Treatment of Depressive Diseases, Changsha 410208, China
Published: 2025-12-12 doi: 10.16438/j.0513-4870.2025-0589
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Depression, a highly disabling psychiatric disorder, involves core disruptions in the epigenetic regulation (DNA methylation, histone modifications, non-coding RNA) of circadian clock genes (e.g., circadian locomotor output cycles kaput, brain and muscle ARNT-like protein 1, period, and cryptochrome). This dysregulation causes abnormal gene expression rhythms, leading to neurotransmitter imbalance, hypothalamic-pituitary-adrenal axis overactivation, and exacerbated neuroinflammation. We propose an "epigenetic-clock-neural circuit" interaction model, wherein suprachiasmatic nucleus master clock dysfunction disrupts synchronization of the hypothalamic-hippocampal-prefrontal circuit, constituting the core mechanism of emotional-cognitive comorbidity. Depression exhibits distinct circadian epigenetic signatures compared to epilepsy or dementia, revealing disease-specific mechanisms. Animal and clinical evidence converge on the pivotal role of circadian epigenetics. Diverse therapeutic strategies target this mechanism, including antidepressants, small-molecule inhibitors, behavioral interventions, gene editing/RNA therapies, and biomarker-guided personalized medicine. Treatment is evolving from generalized to personalized approaches, requiring novel targets and technologies. Despite challenges, this groundbreaking research opens new diagnostic and therapeutic avenues, advancing psychiatry into an era of "circadian medicine".

depression  /  circadian clock gene  /  epigenetic regulation  /  precision medicine  /  neural circuit
戴佳程, 邹蔓姝, 贺海霞, 王宇红. 抑郁症生物钟基因的表观调控: 多维度机制与精准治疗转化. 药学学报, 2025 , 60 (12) : 3665 -3681 . DOI: 10.16438/j.0513-4870.2025-0589
Jia-cheng DAI, Man-shu ZOU, Hai-xia HE, Yu-hong WANG. Epigenetic regulation of circadian clock genes in depression: multidimensional mechanisms and translational precision therapeutics[J]. Acta Pharmaceutica Sinica, 2025 , 60 (12) : 3665 -3681 . DOI: 10.16438/j.0513-4870.2025-0589
Year 2025 volume 60 Issue 12
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Article Info
doi: 10.16438/j.0513-4870.2025-0589
  • Receive Date:2025-05-26
  • Online Date:2026-09-20
  • Published:2025-12-12
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History
  • Received:2025-05-26
  • Revised:2025-07-18
Affiliations
    1Academy of Chinese Medical Sciences, Hunan University of Traditional Chinese Medicine, Changsha 410208, China
    2First Affiliated Hospital, Hunan University of Traditional Chinese Medicine, Changsha 410007, China
    3Hunan Key Laboratory of Traditional Chinese Medicine Prevention and Treatment of Depressive Diseases, Changsha 410208, China
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表12种不同金属材料的力学参数
科
Family
属数
Number of
genus
种数
Number of
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Percentage of
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Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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