Circadian Immune Rhythmicity Failure: A Mast Cell Mechanism Linking Artificial Light at Night to Inflammatory Chronic Disease – With a Proposed Explanation for the Cross-Syndrome Efficacy of Antidepressants, Antihistamines, and Metformin

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.