Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The isoprenoid pathway and its metabolites--digoxin, dolichol and ubiquinone were assessed in schizophrenia. There was an upregulation of the isoprenoid pathway as evidenced by elevated HMG CoA reductase activity. Digoxin, an endogenous Na+-K+ ATPase inhibitor secreted by the hypothalamus was found to be elevated and RBC membrane Na+-K+ ATPase activity was found to be reduced in schizophrenia. Membrane Na+-K+ ATPase inhibition can result in increased intracellular Ca2+ and reduced magnesium levels. Hypothalamic digoxin can modulate conscious and subliminal perception and its dysfunction may lead on to schizophrenia. Digoxin can also preferentially upregulate tryptophan 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 noradrenaline contributing to membrane Na+-K+ ATPase inhibition. NMDA excitotoxicity could result from hypomagnesemia induced by membrane Na+-K+ ATPase inhibition and quinolinic acid, an NMDA agonist acting on the NMDA receptor. Hypomagnesemia and increased dolichol level can affect glycoconjugate metabolism and membranogenesis leading on to disordered synaptic connectivity in the limbic allocortex and defective presentation of viral antigens and neuronal 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 consequent to altered calcium/magnesium ratios and reduced ubiquinone levels can result in increased free radical generation and reduced free radical scavenging & defective apoptosis leading on to abnormal synaptogenesis. Schizophrenia can thus be considered as a syndrome of hypothalamic digoxin hypersecretion consequent to an upregulated isoprenoid pathway.
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PMID:A hypothalamic digoxin mediated model for conscious and subliminal perception. 1151 51

Alteration in the isoprenoid metabolites--digoxin, ubiquinone, and dolichol--have been reported in neuronal degeneration (Parkinson's disease), oncogenesis (central nervous system glioma), functional neuropsychiatric disorders (schizophrenia and epilepsy), and immune-mediated disorders (multiple sclerosis). The coexistence of these disorders has been documented in literature and a central dysfunction related to digoxin and the isoprenoid pathway may underlie all these disorders. A family with a high prevalence of Parkinson's disease, schizophrenia, neoplasms, syndrome X, rheumatoid arthritis, and epilepsy has been described. The psychological behavioral patterns of the family were: creativity and high IQ, hypersexual behavior, reduced appetite and eating behavior, insomnia and reduced sleep patterns, increased tendency for spirituality, increased tendency for addiction, less bonding and affectionate behavior, and left handedness/right hemispheric dominance. Digoxin, an endogenous Na(+)-K+ ATPase inhibitor secreted by the hypothalamus, was found to be elevated and red blood cell (RBC) membrane Na(+)-K+ ATPase activity was found to be reduced in all the disorders and in the indexed family studied. Hypothalamic digoxin can modulate conscious perception and its dysfunction may lead to schizophrenia. Digoxin can also preferentially upregulate tryptophan transport over tyrosine, resulting in increased levels of depolarizng tryptophan catabolites, serotonin, quinolinic acid, strychnine, and nicotine, and decreased levels of hyperpolarizing tyrosine catabolites, dopamine, noradrenaline, and morphine, contributing to membrane Na(+)-K+ ATPase inhibition in all the above disorders and the indexed family. Digoxin-induced membrane Na(+)-K+ ATPase inhibition can result in increased intracellular Ca2+ and reduced Mg2+ levels, leading on to glutamate excitotoxicity, oncogene activation, and immune activation. Digoxin-induced altered Ca2+/Mg2+ ratios, reduced ubiquinone, and increased dolichol can affect glycoconjugate metabolism, membrane formation and structure, and mitochondrial function, leading to the diverse disorders described above, including those in the indexed family. The isoprenoid pathway and neurotransmitter patterns were compared in right-handed/LH dominant and left-handed/RH dominant individuals. The left-handed/RH dominant individuals compared to right-handed/LH dominant individuals had elevated hydroxymethylglutarylcoenzyme A reductase activity, with increased serum digoxin and dolichol levels. The serum ubiquinone, serum Mg2+ and RBC Na(+)-K+ ATPase activity were reduced in left-handed/RH dominant individuals. The left-handed/RH dominant individuals compared to right-handed/LH dominant individuals had elevated levels of serum tryptophan, quinolinic acid, serotonin, nicotine, and strychnine. The levels of tyrosine, dopamine, noradrenaline, and morphine were low in left-handed/RH dominant compared to right-handed/LH dominant individuals. The hyperdigoxinemic state indicates right hemispheric dominance. Hypothalamic digoxin can thus function as the master conductor of the neuroimmunoendocrine orchestra and coordinate the functions of various cellular organelles.
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PMID:Central role of hypothalamic digoxin in conscious perception, neuroimmunoendocrine integration, and coordination of cellular function: relation to hemispheric dominance. 1232 12

The isoprenoid pathway produces digoxin, an endogenous membrane Na(+)-K+ ATPase inhibitor and regulator of neurotransmitter transport. The objective of the study was to relate digoxin status and hemispheric dominance to the pathogenesis of psychiatric disorders--bipolar mood disorder, major depressive disorder, and schizophrenia. The following parameters were assessed in bipolar mood disorder during the manic phase and depressive phase of the illness as well as in major depressive disorder, and schizophrenia: HMG CoA reductase activity, tryptophan and tyrosine catabolic patterns, red blood cell (RBC) Na(+)-K+ ATPase activity, and serum magnesium. These parameters were compared to individuals of differing hemispheric dominance. The levels of serum digoxin and HMG CoA reductase activity were found to be decreased in the depressive phase of bipolar mood disorder and major depressive disorder with a corresponding increase in RBC Na(+)-K+ ATPase activity and serum magnesium levels. There was increase in tyrosine and tyrosine catabolites, and a reduction in tryptophan and its catabolites, in the serum in the depressive phase of bipolar mood disorder and major depressive disorder. The neurotransmitter patterns and digoxin levels in the depressive phase of bipolar mood disorder/major depressive disorder correlated with those in right-handed/left hemisphere dominant individual. The neurotransmitter patterns and digoxin levels in the manic phase of bipolar mood disorder and schizophrenia correlated with those in left-handed/right hemisphere dominant individuals. Digoxin status and hemispheric dominance could correlate with the pathogenesis of psychiatric disorders--schizophrenia, major depressive disorder, and bipolar mood disorder.
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PMID:Membrane Na(+)-K+ ATPase mediated cascade in bipolar mood disorder, major depressive disorder, and schizophrenia--relationship to hemispheric dominance. 1244 37

A family with a high prevalence of Parkinson's disease, schizophrenia, neoplasms, syndrome-X, rheumatoid arthritis and epilepsy has been described. The psychological behavioural patterns of the family were as follows--creativity and high IQ, hypersexual behaviour, reduced appetite and eating behaviour, insomnia and reduced sleep patterns, increased tendency for spirituality, increased tendency for addiction, less of bonding and affectionate behaviour and left handedness. Digoxin, an endogenous Na(+)-K(+) ATPase inhibitor secreted by the hypothalamus, was found to be elevated and RBC membrane Na(+)-K(+) ATPase activity was found to be reduced in all the disorders and in the indexed family studied. Hypothalamic digoxin can modulate conscious perception and its dysfunction may lead to schizophrenia. Digoxin can also preferentially upregulate tryptophan transport over tyrosine resulting in increased levels of depolarising tryptophan catabolites - serotonin, quinolinic acid, strychnine and nicotine and decreased levels of hyperpolarising tyrosine catabolites dopamine, noradrenaline and morphine contributing to membrane Na(+)-K(+) ATPase inhibition in all the above disorders and the indexed family. Digoxin induced membrane Na(+)-K(+) ATPase inhibition can result in increased intracellular Ca(2+) and reduced Mg(++) levels leading to glutamate excitotoxicity, oncogene activation and immune activation. Digoxin induced altered Ca(++)/Mg(++) ratios, reduced ubiquinone and increased dolichol can affect glycoconjugate metabolism, membrane formation and structure and mitochondrial function leading to the diverse disorders described above including those in the indexed family. The isoprenoid pathway and neurotransmitter patterns were compared in right-handed/left hemispheric dominant and left-handed/right hemispheric dominant individuals. The biochemical patterns in the indexed family and the diverse disorders studied correlated with those obtained in right hemispheric dominance. The hyperdigoxinemic state indicates right hemispheric dominance. Hypothalamic digoxin can thus function as the master conductor of the neuroimmunoendocrine orchestra and co-ordinate the functions of various cellular organelles.
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PMID:Hypothalamic digoxin--central role in conscious perception, neuroimmunoendocrine integration and coordination of cellular function--relation to hemispheric dominance. 1260 43

The case report of a family with coexistence of schizophrenia, systemic malignancy, Parkinson's disease, rheumatoid arthritis and syndrome X is described. The coexistence of malignant transformation, neuronal degeneration, immune dysfunction and psychiatric manifestation have been extensively documented in literature. It is possible that a central dysfunction in neuroendocrine and immune integration may play a role in the pathophysiology of these diseases. Elevated levels of an endogenous sodium-potassium ATPase inhibitor, digoxin, a steroidal glycoside, has been reported in syndrome X. The human hypothalamus is the principal source of digoxin. Serum digoxin level and RBC sodium-potassium ATPase were measured in the members of the index family and8 groups of patients with CNS gliomas, Parkinson's disease, motor neuron disease, CNS vasculitis, multiple sclerosis, primary generalised epilepsy, schizophrenia and the acquired immunodeficiency syndrome. Digoxin, being a isoprenoidal compound, its synthesis was assessed by HMG CoA reductase activity. The levels of serum digoxin and HMG CoA reductase activity were found to be increased in the members of the index family and all the 8 groups studied with a corresponding reduction in RBC sodium-potassium ATPase activity. The role of hypothalamic digoxin in the pathogenesis of these diseases is discussed. A digoxin model for hypothalamic regulation of neuronal transmission, endocrine function, immunity and cytodifferentiation is proposed.
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PMID:Digoxin : a model for hypothalamic regulation of neuronal transmission, endocrine function, immunity and cytodifferentiation. 2950 17