#031 On Depression and Its Underlying Causes

Inflammation directly causes depressive symptoms

Rhonda Patrick presents causal evidence from placebo-controlled studies showing that injecting healthy people with inflammatory cytokines causes acute depressive symptoms, anxiety, and anhedonia - and that EPA omega-3 fatty acids block these effects.

"Those people that were injected with the pro-inflammatory cytokine, but were also given the omega-3 fatty acid known as icosapentaenoic acid or EPA that I have talked about for a variety of reasons and is known for its renowned anti-inflammatory properties, did not experience depressive symptoms."

Exercise prevents neurotoxic metabolite linked to depression

Patrick explains how inflammation diverts tryptophan away from serotonin production into a neurotoxic compound called quinolinic acid, but exercise causes skeletal muscle to intercept this pathway and prevent the neurotoxin from forming.

"In humans, exercise has been shown to cause kynurinine to be taken up into muscle and prevents it from becoming this toxic metabolite, which provides yet another possible mechanism by which exercise combats depression."

Stress hormones degrade gut lining and fuel brain inflammation

Patrick describes how stress hormones like cortisol and CRH travel to the gut, activate mast cells, release pro-inflammatory cytokines, degrade gut epithelium proteins causing intestinal permeability, and activate the inflammasome which directly connects to brain inflammation.

"Corticotropin-releasing hormone, which makes its way into the gut, perhaps the vagus nerve, the direct line between the gut and the brain. Once it's in the gut, the stress hormone activates immune cells in the gut, specifically called mast cells, and they release pro-inflammatory cytokines like TNF-alpha"