ubiquinone and Mental-Disorders

Topics: Humans; Mental Disorders; Mitochondria; Nervous System Diseases; Oxidative Stress; Randomized Controlled Trials as Topic; Schizophrenia; Treatment Outcome; Ubiquinone; Vitamins

Coenzyme Q10 (CoQ10) is an antioxidant, a membrane stabilizer, and a vital cofactor in the mitochondrial electron transport chain, enabling the generation of adenosine triphosphate. It additionally regulates gene expression and apoptosis; is an essential cofactor of uncoupling proteins; and has anti-inflammatory, redox modulatory, and neuroprotective effects. This paper reviews the known physiological role of CoQ10 in cellular metabolism, cell death, differentiation and gene regulation, and examines the potential repercussions of CoQ10 depletion including its role in illnesses such as Parkinson's disease, depression, myalgic encephalomyelitis/chronic fatigue syndrome, and fibromyalgia. CoQ10 depletion may play a role in the pathophysiology of these disorders by modulating cellular processes including hydrogen peroxide formation, gene regulation, cytoprotection, bioenegetic performance, and regulation of cellular metabolism. CoQ10 treatment improves quality of life in patients with Parkinson's disease and may play a role in delaying the progression of that disorder. Administration of CoQ10 has antidepressive effects. CoQ10 treatment significantly reduces fatigue and improves ergonomic performance during exercise and thus may have potential in alleviating the exercise intolerance and exhaustion displayed by people with myalgic encepholamyletis/chronic fatigue syndrome. Administration of CoQ10 improves hyperalgesia and quality of life in patients with fibromyalgia. The evidence base for the effectiveness of treatment with CoQ10 may be explained via its ability to ameliorate oxidative stress and protect mitochondria.

Topics: Humans; Mental Disorders; Nitrosation; Oxidative Stress; Signal Transduction; Ubiquinone

Though affecting many thousands of patients, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) should be considered an orphan disease, since the cause remains elusive and no treatment is available that can provide complete cure. There is reasonable insight into the pathogenesis of signs and symptoms, and treatments specifically directed to immunological, inflammatory and metabolic processes offer relief to an increasing number of patients. Particular attention is given to the importance of co-morbidity requiring appropriate therapy. Promising results are obtained by treatment with Metformin, or possibly Momordica charantia extract, which will correct insulin resistance, with Meldonium improving the transportation of glucose into the mitochondria, with sodium dichloroacetate activating pyruvate dehydrogenase, and with nutraceutical support reducing oxidative and inflammatory impairment.

Topics: Adult; Animals; Antiviral Agents; Autoimmune Diseases; Comorbidity; Dichloroacetic Acid; Dietary Supplements; Drug Evaluation, Preclinical; Drug Therapy, Combination; Endocrine System Diseases; Fatigue Syndrome, Chronic; Female; Humans; Infections; Insulin Resistance; Male; Mental Disorders; Methylhydrazines; Middle Aged; Mitochondria; Neuroimaging; Pyruvate Dehydrogenase Complex; Severity of Illness Index; Thiamine; Thioctic Acid; Tomography, Emission-Computed, Single-Photon; Ubiquinone

Mental disorders present a global health concern and have limited treatment options. In today's medical practice, medications such as antidepressants are prescribed not only for depression but also for conditions such as anxiety and attention deficit hyperactivity disorder (ADHD). Therefore, identifying gene targets for specific disorders is important and offers improved precision. In this study, we performed a genetic analysis of six common mental disorders-ADHD, anxiety, depression, delays in mental development, intellectual disabilities (IDs) and speech/language disorder-in the ethnic minority of African Americans (AAs) using whole genome sequencing (WGS). WGS data were generated from blood-derived DNA from 4178 AA individuals, including 1384 patients with the diagnosis of at least one mental disorder. Mutation burden analysis was applied based on rare and deleterious mutations in the AA population between cases and controls, and further analyzed in the context of patients with single mental disorder diagnosis. Certain genes uncovered demonstrated significant P-values in mutation burden analysis. In addition, exclusive recurrences in specific type of disorder were scanned through gene-drug interaction databases to assess for availability of potential medications. We uncovered 15 genes harboring deleterious mutations, including 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR) and Uronyl 2-Sulfotransferase (UST) for ADHD; Farnesyltransferase, CAAX Box, Beta (FNTB) for anxiety; Xin Actin Binding Repeat Containing 2 (XIRP2), Natriuretic Peptide C (NPPC), Serine/Threonine Kinase 33 (STK33), Pannexin 1 (PANX1) and Neurotensin (NTS) for depression; RUNX Family Transcription Factor 3 (RUNX3), Tachykinin Receptor 1 (TACR1) and NADH:Ubiquinone Oxidoreductase Core Subunit S7 (NDUFS7) for delays in mental development; Hepsin (HPN) for ID and Collagen Type VI Alpha 3 Chain (COL6A3), Damage Specific DNA Binding Protein 1 (DDB1) and NADH:Ubiquinone Oxidoreductase Subunit A11 (NDUFA11) for speech/language disorder. Taken together, we have established critical insights into the development of new precision medicine approaches for mental disorders in AAs.

Topics: Attention Deficit Disorder with Hyperactivity; Black or African American; Connexins; Ethnicity; Humans; Language Disorders; Mental Disorders; Minority Groups; Mutation; NAD; Nerve Tissue Proteins; Oxidoreductases; Ubiquinone; Whole Genome Sequencing

The membrane composition and the isoprenoid pathway metabolites important in maintaining cell membrane integrity was studied in neurological and psychiatric disorders. The results indicate alteration in cholesterol:phospholipid ratio of the RBC membrane which is increased in glioma, schizophrenia, and bipolar mood disorder (MDP); decreased in multiple sclerosis and Parkinson's disease; and not significantly altered in epilepsy. The concentration of total glycosaminoglycans (GAG), hexose, and fucose decreased in the RBC membrane and increased in the serum. The RBC membrane Na+-K+ ATPase activity was reduced and serum HMG CoA reductase activity was increased. There were increased serum levels of digoxin, cholesterol, and dolichol and decreased levels of ubiquinone. The serum magnesium and tyrosine levels were reduced and tryptophan increased. The results indicate a defect in membrane formation and a decreased membrane Na+-K+ ATPase activity in all the disorders studied. The results are discussed, and a hypothesis regarding the relationship between these disorders and defective membrane architecture and membrane Na+-K+ ATPase inhibition is presented.

Topics: Adult; Cholesterol; Digoxin; Dolichols; Erythrocyte Membrane; Female; Humans; Hydroxymethylglutaryl CoA Reductases; Male; Membrane Proteins; Mental Disorders; Middle Aged; Models, Biological; Nervous System Diseases; Neurons; Phospholipids; Sodium-Potassium-Exchanging ATPase; Terpenes; Tryptophan; Tyrosine; Ubiquinone

The isoprenoid pathway produces three key metabolites--digoxin (membrane Na(+)-K+ ATPase inhibitor, regulator of neurotransmitter transport, and immunomodulatory agent), dolichol (regulatory of N-glycosylation of proteins), and ubiquinone (free-radical scavenger). The pathway was assessed in systemic lupus erythematosis with neuropsychiatric manifestations, slow viral diseases (subacute sclerosing panencephalitis [SSPE], and Creutzfeldt-Jakob disease [CJD]) and patients with recurrent respiratory infections. This was also studied for comparison in patients with right hemispheric and left hemispheric dominance. The isoprenoid pathway was upregulated with increased digoxin synthesis in patients with neurolupus, SSPE, and CJD, and in those with right hemispheric dominance. The tryptophan catabolites were increased and the tyrosine catabolites reduced. In these patients the dolichol and glycoconjugate levels were elevated and lysosomal stability was reduced. The ubiquinone levels were low and free-radical levels increased in these patients. The membrane cholesterol:phospholipid ratios were increased and membrane glycoconjugates reduced. On the other hand, in patients with recurrent respiratory infection and left hemispheric dominance, the reverse patterns and hypodigoxinemia with a downregulated isoprenoid pathway were noticed. The isoprenoid pathway is important in the pathogenesis of neurolupus, CJD, SSPE, and recurrent respiratory infections. Hypothalamic digoxin and chemical hemispheric dominance play an important role in the regulation of immunity.

Topics: Creutzfeldt-Jakob Syndrome; Digoxin; Dolichols; Erythrocyte Membrane; Functional Laterality; Glycosaminoglycans; Humans; Hydroxymethylglutaryl CoA Reductases; Hypothalamus; Lupus Erythematosus, Systemic; Mental Disorders; Neuroimmunomodulation; Recurrence; Respiratory Tract Diseases; Sodium-Potassium-Exchanging ATPase; Subacute Sclerosing Panencephalitis; Tryptophan; Tyrosine; Ubiquinone

The incidence of coenzyme Q 10 and its alterations in psychiatrical pathology is studied. A screening of a randomly selected 113-patient sample showed a high percentage of deficiencies: When taken care of, an improvement in patients' clinical pictures, with no secondary complaint could be observed. Results do not yield alteration specificity according to diagnosis. In those cases where values higher than admitted as normal were detected, neither a common symptoms nor the predomination of a determined pathology could be found.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Chromatography, High Pressure Liquid; Female; Humans; Male; Mental Disorders; Middle Aged; Ubiquinone

Topics: Animals; Coenzymes; Cytoplasm; Liver; Mental Disorders; Rats; Stress, Physiological; Ubiquinone