Neurotoxic metabolites of kynurenine are likely primary contributors to depression genesis in the context of inflammation.

“what's basically happening here is that the tryptophan that normally would be made into serotonin, under conditions of inflammation is being diverted into a neurotoxic pathway.”

“And ingestion of EPAs, because it limits these inflammatory cytokines, things like IL-6, C-reactive protein, et cetera, can cause more of the tryptophan that one ingests or has in their body to be diverted towards the serotoninergic pathway.”

“However, if there's excessive amounts of inflammation, these inflammatory cytokines cause tryptophan to be diverted down a different pathway. The pathway involves something called IDO, indoleamine, which converts tryptophan into kynurenine. Kynurenine actually acts as a neurotoxin by way of converting into something called quinolinic acid, okay? And quinolinic acid is pro-depressive.”

“the inflammation can trigger shunting of tryptophan metabolites to other spaces in the body and then you don't always make enough serotonin”

“So really, it looks like exactly is that kynurenine and its metabolites almost, I mean, those are results that have been replicated. But they’re probably more relevant bad actors through that pathway in terms of the depression genesis in the context of inflammation than is the drop in serotonin.”

“But the problem is that kynurenine can form is it quinolinic acid? Charles: You can find kynurenic acid and quinolinic acid, that’s right. Quinolinic acid is definitely a neurotoxic agent.”

“So Michael Moss and Lucile Capuron, and a number of people in the early 2000s, began to show that chronic inflammation activated an enzyme called Indoleamine 2,3-Dioxygenase. This is an enzyme that basically, as you said, takes tryptophan and shunts it away from serotonin into kynurenine.”

“canine is a compound that can be converted into a metabolite that is actually neurotoxic and associated with Depression known as quinolinic acid”

“in the case of Serotonin the inflammatory cyto kindes such as tnf Alpha actually increase the metabolism or re-uptake of Serotonin and thus decrease the amount of Serotonin that's actively in the synapse where it exerts all of its effects on mood and anxiety inflammatory cyto kindes also lower the amount of Serotonin that is produced by diverting the precursor to serotonin tryptophan into a competing pathway through the activation of an enzyme called indolamine 23 dioxygenase or Ido which is responsible for converting tryptophan into curine instead of Serotonin”