OCD AND PYRUVATE DEHYDROGENASE
By JOHN STEWART
As set out in NPBR.1. and JBI.2., MAOI OCD cure involves gut TRPA1 activation by radicals*,and vagal/trigeminal change influencing the parabrachial and subthalamic nuclei.3. The subthalamic nucleus is implicated in OCD.4. with ventral subthalamic theta activity inversely-correlated with OCD severity.5. Vagal feedback disruption, with consequently increased pyruvate dehydrogenase complex(PDC) activation by dephosphorylation, reverses brain hypometabolism. Astrocyte dysfunction in OCD.6. suggests increased PDC activation may be significant for OCD cure not only for the TCA cycle and brain energy metabolism, but also linked glutamate-glutamine-GABA cycling, and resultant changes to excitatory/inhibitory balances in neurons. Neurons depend upon this cycling to replenish glutamate via glutamine from astrocytes. Disordered astrocyte/neuronal coupling is seen in the OCD-related Tourette's syndrome, with significant negative correlations between thalamic glutamate levels and premonitory urges.7. Further, pyruvate kinase M1 is an autoimmune target in Tourette's.8.;this immunoreactivity may be clinically relevant to Tourette's and OCD.
*(Sleep deprivation, frequently found antidepressant in humans, has recently been found to cause large free radical increases in mammalian small and large intestines.9.,which may explain this.)
1.Neurology,Psychiatry and Brain Research.5(4):181,8(4):185,10(4):149.
2.Journal of Brief Ideas."OCD,TRPA1s and the vagal fear pathway" 3.Nature.Communications.2021;12:2648. 4.J.Neurol.Neurosurg.Psychiatry.2020;91:1349-1356. 5.Translational Psychiatry.2018.8:118.
6.Experimental & Molecular Medicine.2020.52:1028-1038.