Circadian Immune Rhythmicity Failure: A Mast Cell Mechanism Linking Artificial Light at Night to Inflammatory Chronic Disease
Year: 2026
Type: preprint
Abstract: Note (June 2026): This paper has been superseded by Version 2, published on Figshare as part of the CIRP — Circadian Immune Rhythmicity Project series. Version 2 (Figshare): https://doi.org/10.6084/m9.figshare.32593446 All five papers in the series are available at: https://figshare.com/projects/CIRP_-_Circadian_Immune_Rhythmicity_Project/276495 This Version 1 remains available for reference. Artificial light at night (ALAN) is associated with depression (3.29% risk increase per 1 lux indoor exposure; dose-response, 560,219 participants), allergic disease (OR 1.88), breast cancer (RR 1.12), and broad multimorbidity across virtually all major disease categories. Global nighttime brightness is increasing at 9.6% per year. Smartphone screens deliver indoor ALAN at retinal-stimulating intensities, directly before sleep; screen time ≥4 hours/day is associated with depression (OR 1.61), anxiety (OR 1.45), and ADHD (OR 1.21) in children — mediated primarily by sleep timing irregularity, not sleep duration. These associations are epidemiologically robust but mechanistically unexplained — treated as separate phenomena by separate fields. We propose a single upstream mechanism: collapse of circadian light-dark amplitude eliminates the melatonin-mediated nocturnal resetting cycle of mast cells, producing chronic low-grade mast cell activation that manifests across organ systems according to individual genetic and tissue context. A self-sustaining feedback loop — in which mast cell-derived TNF-α suppresses both SCN clock gene expression and pineal AANAT, further reducing melatonin synthesis — explains chronification and treatment resistance. This mechanism predicts and explains a second, independent observation: the major antidepressant classes — SSRIs, tricyclics, mirtazapine, SNRIs — all stabilize mast cells through distinct off-target pathways, independent of their putative neurotransmitter mechanisms. Each step is independently evidenced in published literature. The synthesis is new.
Author: Vester, Julian
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7162806684
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