Figure 6.

The overactive KP affects the serotonin pathway. The aryl hydrocarbon receptor (AHR) has a role in regulating immunity and induce transcription of indoleamine 2,3-dioxygenase (IDO-2) enzyme. The amount of IDO-2 in PCS is abundant and causes autophagy and reduced mitochondrial functioning²⁸. Because the metabolites kynurenine and kynurenine acid are agonists of the AHR receptor, there is a ‘runaway positive feedback loop’ producing more and more metabolites^28,30–32. Several of the metabolites are potentially toxic. Kynurenine and oxidative stress block the enzyme tetrahydrobiopterin (BH4)^1,56, inhibiting both the serotonin pathway and the dopamine pathway^1,20,55,56. Kynurenic acid is a nicotine-receptor antagonist and a glutaminergic-receptor antagonist^28,30,32. Quinolinic acid blocks the glutaminergic receptor²⁸. When we want to intervene: the kynurenine pathway can be inhibited in various ways and the serotonin pathway can be stimulated in various ways. Intervening through an SSRI has been the most important so far.