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What Is Depression, Anyway?: The Synapse Hypothesis | Slate Star Codex

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The problem with depression research isn’t that we don’t have any leads on what causes depression. It’s that we have so many leads on what causes depression that we don’t know what to do with all of them. For example: 1. Life adversity, like getting fired or breaking up with a partner, can make people depressed. The biological correlate of this seems to be the hypothalamic–pituitary–adrenal axis (HPA), where your brain tells your adrenal glands to produce glucocorticoid stress hormones like cortisol and this does something to your brain that increases the risk of depression. 2. Inflammation and immune overactivity can make people depressed. The classic examples of this are cancer-related depression (which exceeds what you would expect just from cancer being stressful) and depression induced by administration of the immunomodulator interferon-a. Antiinflammatory drugs have a small but clinically relevant antidepressant effect. Some of the relevant chemicals here seem to be TNF-A and IL-

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