Key points

Scientists mapped chromatin accessibility in brain cells from people with and without major depression.

Two cell types stood out: deep-layer excitatory neurons and a gray-matter microglia subtype.

Depression is not only a chemical imbalance but a rewiring of the brain’s regulation of genes.

Depression affects millions worldwide, yet its root cause has long remained elusive. Behind its lived experience lies a biological mystery. Why does the brain, an organ built to adapt and survive, sometimes disrupt its own careful harmony?

For decades, the dominant story was simple: a “chemical imbalance,” a shortage of serotonin or dopamine . That story is comforting in its clarity, yet incomplete. Antidepressants can ease symptoms, yet they do not explain why depression begins, or

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