OCD, TRPA1s, AND THE VAGAL FEAR PATHWAY.
By JOHN STEWART
As mentioned in articles in NPBR.1. and JBI.2., the crucial stage in MAOI and St John' s Wort OCD cures I have repeatedly found to be strong TRPA1 receptor activation by radicals, resulting in gut serotonin and CCK release. Matsuo et al.3. have pointed out that the TRPA1 vagal/trigeminal innate fear pathway, demonstrated in animals, is conserved in humans, including the vagal solitary tract nucleus path to the midbrain parabrachial nucleus. Vagal activation of this fear pathway leads to hypometabolism in brain areas due to suppression of pyruvate dehydrogenase activity by phosphorylation.
OCD cure, as detailed earlier, appears to relate to disruption of vagal afferent feedback, and resulting reversal of brain hypometabolism in crucial areas could provide increased "neural noise", bringing back the ability to "drown" persistent thoughts and to "mind wander" i.e activation of the default mode network. This hypothesis is testable, given current research into new TRPA1 agonists.
.1. Neurology,Psychiatry and Brain Research 5(4):181, 8(4):185, 10(4):149.
.2. Journal of Brief Ideas. "Oxidative stress, MAOIs and OCD". "OCD, St John's Wort and iron"."OCD, radicals and TRPA1 receptors."
.3. Matsuo et al. Nature Communications. 2021 12(1):2074. / (bioRxiv posted May 19, 2020).