Over the past two decades, researchers such as Maes, Miller, and Raison have helped to bring attention to the role of the immune system in the brain. Inflammatory messengers called cytokines can traffic from the body to the brain, stimulating brain immune cells called microglia and an enzyme called IDO. This stimulation shunts tryptophan from production of serotonin and melatonin to the production of a disruptive excitatory compound called quinolinic acid, at the expense of a more regulatory compound called kynurenic acid. In a paper entitled, “A role for inflammatory metabolites as modulators of the glutamate N-methyl-D-aspartate receptor in depression and suicidality“, researchers measured inflammatory markers in cerebrospinal fluid and metabolites of repeat suicide attempters over a 2 year period.
The proposed physiology addressed in this study may explain the impulsivity involved in suicide-related behavior as quinolinic acid is an NMDA agonist most active in the limbic (think animal brain) system. They conclude:
We demonstrate a long-term dysregulation of the kynurenine pathway in the central nervous system of suicide attempters. An increased load of inflammatory cytokines was coupled to more severe symptoms. We therefore suggest that patients with a dysregulated kynurenine pathway are vulnerable to develop depressive symptoms upon inflammatory conditions, as a result the excess production of the NMDA-receptor agonist quinolinic acid.
Calming and addressing inflammation from the gut, diet, environmental toxins, and stress is becoming a more supported first-line approach, every day. Natural NMDA modulating agents include magnesium, zinc, taurine, glycine, N-acetylcysteine, and phenibut or GABA. Food additives, on the other hand, such as MSG (often hidden under one of these pseudonyms) stimulates the NMDA receptor in a toxic way that can cause unpredictable neurologic symptoms. When we look at the role of antidepressant treatment in suicidality, as exposed by Dr. David Healy, the pharmaceutical approach is revealed to not only miss the mark, but to endanger the very patients who are most vulnerable.