A hypothalamic digoxin mediated model for conscious and subliminal perception

The isoprenoid pathway and its metabolites - digoxin, dolichol and ubiquino ne were assessed in schizophrenia. There was an upregulation of the isopren oid pathway as evidenced by elevated HMG CoA reductase activity. ;Digoxin, an endogenous Na+-K+ ATPase inhibitor secreted by the hypothalamus was foun d to be elevated and RBC membrane Na+-K+ ATPase activity was found to be re duced in schizophrenia. Membrane Na+-K+ ATPase inhibition can result in inc reased intracellular Ca2+ and reduced magnesium levels. Hypothalamic digoxi n can modulate conscious and subliminal perception and its dysfunction may lead on to schizophrenia. Digoxin can also preferentially upregulate trypto phan transport over tyrosine resulting in increased levels of depolarising tryptophan catabolites - serotonin and quinolinic acid (NMDA agonist). and decreased levels of hyperpolarising tyrosine catabolites dopamine and norad renaline contributing to membrane Na+-K+. ATPase inhibition. NMDA excitotox icity could result from hypomagnesemia induced by membrane Na+-K+ ATPase in hibition and quinolinic acid, an NMDA agonist acting on the NMDA receptor. Hypomagnesemia and increased dolichol level can affect glycoconjugate metab olism and membranogenesis leading on to disordered synaptic connectivity in the limbic allocortex and defective presentation of viral antigens and neu ronal antigens contributing to autoimmunity and viral persistance important in the pathogenesis. Membrane Na+-K+ ATPase inhibition can produce immune activation, a component of autoimmunity. Mitochondrial dysfunction conseque nt to altered calcium/ magnesium ratios and reduced ubiquinone levels can r esult in increased free radical generation and reduced free radical scaveng ing & defective apoptosis leading on to abnormal synaptogenesis. Schizophre nia can thus be considered as a syndrome of hypothalamic digoxin hypersecre tion consequent to an upregulated isoprenoid pathway.