Pathogenesis and Treatment of Depression Comorbid with Cerebral Small Vessel Disease Based on the Concept of “Disharmony of the Three Collaterals and Collateral Damage Impairing Mental Activity”

Corresponding author: wudahua

DOI: 10.12201/bmr.202610.00013

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  Abstract: Depression comorbid with cerebral small vessel disease (CSVD) involves cerebral microvascular injury, disrupted white-matter connectivity, and dysfunction of emotion-regulation networks. Previous traditional Chinese medicine studies have mainly interpreted this condition in terms of kidney deficiency and brain-marrow insufficiency, qi deficiency and blood stasis, phlegm-stasis obstruction, and pathogenic factors damaging the brain collaterals. However, the coordinated dysfunction of collateral transmission and regulation, circulation and nourishment, and fluid distribution and clearance requires further integration. Based on collateral disease theory, this article conceptualizes the brain qi, blood, and fluid collaterals as three interrelated functional dimensions of a single brain collateral network. The disease is considered to be rooted in depletion of kidney essence, impaired spleen function, and insufficiency of qi, blood, essence, and fluids. Disharmony of the three collaterals constitutes the core pathological change, collateral damage with brain-marrow injury represents the key link, and dysfunction of mental activity is the functional manifestation. The pathogenesis may be summarized as deficiency and stagnation of the qi collaterals, concurrent disorders of the blood and fluid collaterals, and collateral damage with brain-marrow injury. These patterns may overlap and transform dynamically rather than constituting fixed stages. Treatment should focus on unblocking the collaterals and nourishing the brain marrow. The predominant collateral involvement and the severity of collateral dysfunction, obstruction, and damage should be assessed to determine the relative application of dispersing, resolving, and nourishing methods, while relieving depression and regulating mental activity throughout treatment.

  Key words: cerebral small vessel disease; depression; collateral disease theory; qi collateral; blood collateral; fluid collateral; collateral damage impairing mental activity

  Submit time: 9 October 2026

  Copyright: The copyright holder for this preprint is the author/funder, who has granted biomedRxiv a license to display the preprint in perpetuity.
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  1	2026-08-14	10.12201/bmr.202610.00013V1	Download

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