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Targeting Mitochondrial Dysfunction for Bipolar Disorder

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Bipolar Disorder: From Neuroscience to Treatment

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 48))

Abstract

People with bipolar disorder (BD) all too often have suboptimal long-term outcomes with existing treatment options. They experience relapsing episodes of depression and mania and also have interepisodic mood and anxiety symptoms. We need to have a better understanding of the pathophysiology of BD if we are to make progress in improving these outcomes. This chapter will focus on the critical role of mitochondria in human functioning, oxidative stress, and the biological mechanisms of mitochondria in BD. Additionally, this chapter will present the evidence that, at least for some people, BD is a product of mitochondrial dysregulation. We review the modulators of mitochondria, the connection between current BD medication treatments and mitochondria, and additional medications that have theoretical potential to treat BD.

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References

  • A Pilot Study Investigating the Efficacy of Minocycline and N-Acetyl Cysteine for Bipolar Depression (2016). https://clinicaltrials.gov/ct2/show/NCT02719392

  • A Study by ChromaDex to Assess the Effects of TRU NIAGEN on Cognitive Function, Mood and Sleep in Older Adults (2018). https://clinicaltrials.gov/ct2/show/NCT03562468

  • Abeysundera H, Gill R (2018) Possible SAMe-induced mania. BMJ Case Rep 2018

    Google Scholar 

  • Acuna-Castroviejo D, Escames G, Rodriguez MI et al (2007) Melatonin role in the mitochondrial function. Front Biosci 12:947–963

    CAS  PubMed  Google Scholar 

  • Akarsu S, Bolu A, Aydemir E et al (2018) The relationship between the number of manic episodes and oxidative stress indicators in bipolar disorder. Psychiatry Investig 15:514–519

    CAS  PubMed  PubMed Central  Google Scholar 

  • Alcazar-Fabra M, Trevisson E, Brea-Calvo G (2018) Clinical syndromes associated with coenzyme Q10 deficiency. Essays Biochem 62:377–398

    PubMed  Google Scholar 

  • Allen PJ (2012) Creatine metabolism and psychiatric disorders: does creatine supplementation have therapeutic value? Neurosci Biobehav Rev 36:1442–1462

    CAS  PubMed  PubMed Central  Google Scholar 

  • Almeida OP, Ford AH, Flicker L (2015) Systematic review and meta-analysis of randomized placebo-controlled trials of folate and vitamin B12 for depression. Int Psychogeriatr 27:727–737

    PubMed  Google Scholar 

  • Altunsoy N, Yuksel RN, Cingi Yirun M et al (2018) Exploring the relationship between vitamin D and mania: correlations between serum vitamin D levels and disease activity. Nord J Psychiatry 72:221–225

    PubMed  Google Scholar 

  • Andreazza AC, Shao L, Wang JF et al (2010) Mitochondrial complex I activity and oxidative damage to mitochondrial proteins in the prefrontal cortex of patients with bipolar disorder. Arch Gen Psychiatry 67:360–368

    CAS  PubMed  Google Scholar 

  • Ashok AH, Marques TR, Jauhar S et al (2017) The dopamine hypothesis of bipolar affective disorder: the state of the art and implications for treatment. Mol Psychiatry 22:666–679

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ashton MM, Dean OM, Walker AJ et al (2019) The therapeutic potential of mangosteen pericarp as an adjunctive therapy for bipolar disorder and schizophrenia. Front Psych 10:115

    Google Scholar 

  • Baek JH, Bernstein EE, Nierenberg AA (2013) One-carbon metabolism and bipolar disorder. Aust N Z J Psychiatry 47:1013–1018

    PubMed  Google Scholar 

  • Baltan S (2015) Can lactate serve as an energy substrate for axons in good times and in bad, in sickness and in health? Metab Brain Dis 30:25–30

    CAS  PubMed  Google Scholar 

  • Baranov SV, Baranova OV, Yablonska S et al (2019) Mitochondria modulate programmed neuritic retraction. Proc Natl Acad Sci U S A 116:650–659

    CAS  PubMed  Google Scholar 

  • Bauer IE, Green C, Colpo GD et al (2018) A double-blind, randomized, placebo-controlled study of aspirin and N-acetylcysteine as adjunctive treatments for bipolar depression. J Clin Psychiatry 80

    Google Scholar 

  • Berk M, Copolov DL, Dean O et al (2008) N-acetyl cysteine for depressive symptoms in bipolar disorder--a double-blind randomized placebo-controlled trial. Biol Psychiatry 64:468–475

    CAS  PubMed  Google Scholar 

  • Berk M, Turner A, Malhi GS et al (2019) A randomised controlled trial of a mitochondrial therapeutic target for bipolar depression: mitochondrial agents, N-acetylcysteine, and placebo. BMC Med 17:18

    PubMed  PubMed Central  Google Scholar 

  • Berridge MJ (2014) Calcium signalling and psychiatric disease: bipolar disorder and schizophrenia. Cell Tissue Res 357:477–492

    CAS  PubMed  Google Scholar 

  • Bezafibrate Treatment for Bipolar Depression: A Proof of Concept Study (2015). https://clinicaltrials.gov/ct2/show/NCT02481245

  • Blacker CJ, Lewis CP, Frye MA et al (2017) Metabotropic glutamate receptors as emerging research targets in bipolar disorder. Psychiatry Res 257:327–337

    CAS  Google Scholar 

  • Blazey T, Snyder AZ, Goyal MS et al (2018) A systematic meta-analysis of oxygen-to-glucose and oxygen-to-carbohydrate ratios in the resting human brain. PLoS One 13:e0204242

    PubMed  PubMed Central  Google Scholar 

  • Boden WE, Sidhu MS, Toth PP (2014) The therapeutic role of niacin in dyslipidemia management. J Cardiovasc Pharmacol Ther 19:141–158

    CAS  PubMed  Google Scholar 

  • Bonora M, Patergnani S, Rimessi A et al (2012) ATP synthesis and storage. Purinergic Signal 8:343–357

    CAS  PubMed  PubMed Central  Google Scholar 

  • Brennan BP, Jensen JE, Hudson JI et al (2013) A placebo-controlled trial of acetyl-L-carnitine and alpha-lipoic acid in the treatment of bipolar depression. J Clin Psychopharmacol 33:627–635

    CAS  PubMed  PubMed Central  Google Scholar 

  • Brietzke E, Mansur RB, Subramaniapillai M et al (2018) Ketogenic diet as a metabolic therapy for mood disorders: evidence and developments. Neurosci Biobehav Rev 94:11–16

    CAS  PubMed  Google Scholar 

  • Brown NC, Andreazza AC, Young LT (2014) An updated meta-analysis of oxidative stress markers in bipolar disorder. Psychiatry Res 218:61–68

    CAS  PubMed  Google Scholar 

  • Bustillo JR, Jones T, Qualls C et al (2019) Proton magnetic resonance spectroscopic imaging of gray and white matter in bipolar-I and schizophrenia. J Affect Disord 246:745–753

    PubMed  Google Scholar 

  • Callaly E, Walder K, Morris G et al (2015) Mitochondrial dysfunction in the pathophysiology of bipolar disorder: effects of pharmacotherapy. Mini Rev Med Chem 15:355–365

    CAS  PubMed  Google Scholar 

  • Campbell IH, Campbell H (2019) Ketosis and bipolar disorder: controlled analytic study of online reports. BJPsych Open 5:e58

    PubMed  PubMed Central  Google Scholar 

  • Carney MW, Chary TK, Bottiglieri T et al (1989) The switch mechanism and the bipolar/unipolar dichotomy. Br J Psychiatry 154:48–51

    CAS  PubMed  Google Scholar 

  • Cataldo AM, McPhie DL, Lange NT et al (2010) Abnormalities in mitochondrial structure in cells from patients with bipolar disorder. Am J Pathol 177:575–585

    PubMed  PubMed Central  Google Scholar 

  • Chen S, Owens GC, Edelman DB (2008) Dopamine inhibits mitochondrial motility in hippocampal neurons. PLoS One 3:e2804

    PubMed  PubMed Central  Google Scholar 

  • Chen WT, Huang TL, Tsai MC (2015) Bcl-2 associated with severity of manic symptoms in bipolar patients in a manic phase. Psychiatry Res 225:305–308

    CAS  PubMed  Google Scholar 

  • Chen SD, Wu CL, Hwang WC et al (2017) More insight into BDNF against neurodegeneration: anti-apoptosis, anti-oxidation, and suppression of autophagy. Int J Mol Sci 18:545

    PubMed Central  Google Scholar 

  • Chinnery PF, Hudson G (2013) Mitochondrial genetics. Br Med Bull 106:135–159

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chiu CT, Wang Z, Hunsberger JG et al (2013) Therapeutic potential of mood stabilizers lithium and valproic acid: beyond bipolar disorder. Pharmacol Rev 65:105–142

    CAS  PubMed  PubMed Central  Google Scholar 

  • Clarke DDS (1999) Regulation of cerebral metabolic rate. In: Basic neurochemistry: molecular cellular and medical aspects, 6th edn. Lippincott-Raven, Philadelphia

    Google Scholar 

  • Colle R, de Larminat D, Rotenberg S et al (2017) PPAR-gamma agonists for the treatment of major depression: a review. Pharmacopsychiatry 50:49–55

    CAS  PubMed  Google Scholar 

  • Conze D, Brenner C, Kruger CL (2019) Safety and metabolism of long-term administration of NIAGEN (nicotinamide riboside chloride) in a randomized, double-blind, placebo-controlled clinical trial of healthy overweight adults. Sci Rep 9:9772

    PubMed  PubMed Central  Google Scholar 

  • Cuomo A, Maina G, Bolognesi S et al (2019) Prevalence and correlates of vitamin D deficiency in a sample of 290 inpatients with mental illness. Front Psych 10:167

    Google Scholar 

  • Cuperfain AB, Zhang ZL, Kennedy JL et al (2018) The complex interaction of mitochondrial genetics and mitochondrial pathways in psychiatric disease. Mol Neuropsychiatry 4:52–69

    CAS  PubMed  PubMed Central  Google Scholar 

  • Czerniczyniec A, Bustamante J, Lores-Arnaiz S (2007) Dopamine enhances mtNOS activity: implications in mitochondrial function. Biochim Biophys Acta 1767:1118–1125

    CAS  PubMed  Google Scholar 

  • Data-Franco J, Singh A, Popovic D et al (2017) Beyond the therapeutic shackles of the monoamines: new mechanisms in bipolar disorder biology. Prog Neuro-Psychopharmacol Biol Psychiatry 72:73–86

    CAS  Google Scholar 

  • de Oliveira MR (2015) Vitamin A and retinoids as mitochondrial toxicants. Oxidative Med Cell Longev 2015:140267

    Google Scholar 

  • de Oliveira GS, Cereser KM, Fernandes BS et al (2009) Decreased brain-derived neurotrophic factor in medicated and drug-free bipolar patients. J Psychiatr Res 43:1171–1174

    PubMed  Google Scholar 

  • de Sousa RT, Machado-Vieira R, Zarate CA Jr et al (2014) Targeting mitochondrially mediated plasticity to develop improved therapeutics for bipolar disorder. Expert Opin Ther Targets 18:1131–1147

    PubMed  PubMed Central  Google Scholar 

  • de Sousa RT, Streck EL, Zanetti MV et al (2015) Lithium increases leukocyte mitochondrial complex I activity in bipolar disorder during depressive episodes. Psychopharmacology 232:245–250

    PubMed  Google Scholar 

  • de Sousa CNS, da Silva Leite CMG, da Silva Medeiros I et al (2019) Alpha-lipoic acid in the treatment of psychiatric and neurological disorders: a systematic review. Metab Brain Dis 34:39–52

    PubMed  Google Scholar 

  • Depeint F, Bruce WR, Shangari N et al (2006) Mitochondrial function and toxicity: role of the B vitamin family on mitochondrial energy metabolism. Chem Biol Interact 163:94–112

    CAS  PubMed  Google Scholar 

  • Dhitavat S, Ortiz D, Rogers E et al (2005) Folate, vitamin E, and acetyl-L-carnitine provide synergistic protection against oxidative stress resulting from exposure of human neuroblastoma cells to amyloid-beta. Brain Res 1061:114–117

    CAS  PubMed  Google Scholar 

  • Dienel GA (2012) Brain lactate metabolism: the discoveries and the controversies. J Cereb Blood Flow Metab 32:1107–1138

    CAS  PubMed  Google Scholar 

  • Dogan AE, Yuksel C, Du F et al (2018) Brain lactate and pH in schizophrenia and bipolar disorder: a systematic review of findings from magnetic resonance studies. Neuropsychopharmacology 43:1681–1690

    CAS  PubMed  PubMed Central  Google Scholar 

  • Droge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82:47–95

    CAS  PubMed  Google Scholar 

  • Du F, Yuksel C, Chouinard VA et al (2018) Abnormalities in high-energy phosphate metabolism in first-episode bipolar disorder measured using (31)P-magnetic resonance spectroscopy. Biol Psychiatry 84:797–802

    CAS  PubMed  Google Scholar 

  • Dudley JA, Lee JH, Durling M et al (2015) Age-dependent decreases of high energy phosphates in cerebral gray matter of patients with bipolar I disorder: a preliminary phosphorus-31 magnetic resonance spectroscopic imaging study. J Affect Disord 175:251–255

    CAS  PubMed  Google Scholar 

  • Dudley J, DelBello MP, Weber WA et al (2016) Tissue-dependent cerebral energy metabolism in adolescents with bipolar disorder. J Affect Disord 191:248–255

    CAS  PubMed  Google Scholar 

  • Ear PH, Chadda A, Gumusoglu SB et al (2019) Maternal nicotinamide riboside enhances postpartum weight loss, juvenile offspring development, and neurogenesis of adult offspring. Cell Rep 26:969–983.e964

    CAS  PubMed  Google Scholar 

  • Ebselen as an add-on Treatment in Hypo/Mania (2017). https://clinicaltrials.gov/ct2/show/NCT03013400

  • Effectiveness of Ascorbic Acid and Tocopherol for Depression in Elderly (2016). https://clinicaltrials.gov/ct2/show/NCT02793648

  • Efficacy of Resveratrol in Depression (2017). https://clinicaltrials.gov/ct2/show/NCT03384329

  • Ende G, Cackowski S, van Eijk J et al (2016) Impulsivity and aggression in female BPD and ADHD patients: association with ACC glutamate and GABA concentrations. Neuropsychopharmacology 41:410–418

    CAS  PubMed  Google Scholar 

  • Erecinska M, Silver IA (1989) ATP and brain function. J Cereb Blood Flow Metab 9:2–19

    CAS  PubMed  Google Scholar 

  • Fan L, Feng Y, Chen GC et al (2017) Effects of coenzyme Q10 supplementation on inflammatory markers: a systematic review and meta-analysis of randomized controlled trials. Pharmacol Res 119:128–136

    CAS  PubMed  Google Scholar 

  • Flippo KH, Strack S (2017) Mitochondrial dynamics in neuronal injury, development and plasticity. J Cell Sci 130:671–681

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fonseca AC, Moreira PI, Oliveira CR et al (2015) Amyloid-beta disrupts calcium and redox homeostasis in brain endothelial cells. Mol Neurobiol 51:610–622

    CAS  PubMed  Google Scholar 

  • Forester BP, Harper DG, Georgakas J et al (2015) Antidepressant effects of open label treatment with coenzyme Q10 in geriatric bipolar depression. J Clin Psychopharmacol 35:338–340

    PubMed  PubMed Central  Google Scholar 

  • Forlenza OV, De-Paula VJ, Diniz BS (2014) Neuroprotective effects of lithium: implications for the treatment of Alzheimer's disease and related neurodegenerative disorders. ACS Chem Neurosci 5:443–450

    CAS  PubMed  PubMed Central  Google Scholar 

  • Garrido-Maraver J, Cordero MD, Oropesa-Avila M et al (2014) Clinical applications of coenzyme Q10. Front Biosci (Landmark Ed) 19:619–633

    CAS  Google Scholar 

  • Geddes JR, Miklowitz DJ (2013) Treatment of bipolar disorder. Lancet 381:1672–1682

    CAS  PubMed  Google Scholar 

  • Geoffroy PA, Etain B, Lajnef M et al (2016) Circadian genes and lithium response in bipolar disorders: associations with PPARGC1A (PGC-1alpha) and RORA. Genes Brain Behav 15:660–668

    CAS  PubMed  Google Scholar 

  • Ghaleiha A, Davari H, Jahangard L et al (2016) Adjuvant thiamine improved standard treatment in patients with major depressive disorder: results from a randomized, double-blind, and placebo-controlled clinical trial. Eur Arch Psychiatry Clin Neurosci 266:695–702

    PubMed  Google Scholar 

  • Gladden LB (2004) Lactate metabolism: a new paradigm for the third millennium. J Physiol 558:5–30

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gomes MB, Negrato CA (2014) Alpha-lipoic acid as a pleiotropic compound with potential therapeutic use in diabetes and other chronic diseases. Diabetol Metab Syndr 6:80

    PubMed  PubMed Central  Google Scholar 

  • Gowda U, Mutowo MP, Smith BJ et al (2015) Vitamin D supplementation to reduce depression in adults: meta-analysis of randomized controlled trials. Nutrition 31:421–429

    CAS  PubMed  Google Scholar 

  • Grant JE, Odlaug BL, Chamberlain SR et al (2014) A randomized, placebo-controlled trial of N-acetylcysteine plus imaginal desensitization for nicotine-dependent pathological gamblers. J Clin Psychiatry 75:39–45

    CAS  PubMed  Google Scholar 

  • Greer PL, Greenberg ME (2008) From synapse to nucleus: calcium-dependent gene transcription in the control of synapse development and function. Neuron 59:846–860

    CAS  PubMed  Google Scholar 

  • Grings M, Moura AP, Parmeggiani B et al (2017) Bezafibrate prevents mitochondrial dysfunction, antioxidant system disturbance, glial reactivity and neuronal damage induced by sulfite administration in striatum of rats: implications for a possible therapeutic strategy for sulfite oxidase deficiency. Biochim Biophys Acta Mol basis Dis 1863:2135–2148

    CAS  PubMed  Google Scholar 

  • Grob CS, Danforth AL, Chopra GS et al (2011) Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry 68:71–78

    CAS  PubMed  Google Scholar 

  • Guimaraes-Ferreira L (2014) Role of the phosphocreatine system on energetic homeostasis in skeletal and cardiac muscles. Einstein (Sao Paulo) 12:126–131

    Google Scholar 

  • Guo C, Sun L, Chen X et al (2013) Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regen Res 8:2003–2014

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hagen TM, Liu J, Lykkesfeldt J et al (2002) Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Proc Natl Acad Sci U S A 99:1870–1875

    CAS  PubMed  PubMed Central  Google Scholar 

  • Haghighatdoost F, Hariri M (2019) The effect of alpha-lipoic acid on inflammatory mediators: a systematic review and meta-analysis on randomized clinical trials. Eur J Pharmacol 849:115–123

    CAS  PubMed  Google Scholar 

  • Hammerling U (2016) Retinol as electron carrier in redox signaling, a new frontier in vitamin a research. Hepatobiliary Surg Nutr 5:15–28

    PubMed  PubMed Central  Google Scholar 

  • Hardeland R (2017) Melatonin and the electron transport chain. Cell Mol Life Sci 74:3883–3896

    CAS  PubMed  Google Scholar 

  • Harwood AJ (2005) Lithium and bipolar mood disorder: the inositol-depletion hypothesis revisited. Mol Psychiatry 10:117–126

    CAS  PubMed  Google Scholar 

  • Haybaeck J, Postruznik M, Miller CL et al (2015) Increased expression of retinoic acid-induced gene 1 in the dorsolateral prefrontal cortex in schizophrenia, bipolar disorder, and major depression. Neuropsychiatr Dis Treat 11:279–289

    PubMed  PubMed Central  Google Scholar 

  • Herlihy WC (2011) Repligen reports phase 2b results for RG2417 for bipolar depression. https://www.businesswire.com/news/home/20110307005868/en/Repligen-Reports-Phase-2b-Results-RG2417-Bipolar

  • Holper L, Ben-Shachar D, Mann JJ (2019) Multivariate meta-analyses of mitochondrial complex I and IV in major depressive disorder, bipolar disorder, schizophrenia, Alzheimer disease, and Parkinson disease. Neuropsychopharmacology 44:837–849

    CAS  PubMed  Google Scholar 

  • Howell N, Smejkal CB, Mackey DA et al (2003) The pedigree rate of sequence divergence in the human mitochondrial genome: there is a difference between phylogenetic and pedigree rates. Am J Hum Genet 72:659–670

    CAS  PubMed  PubMed Central  Google Scholar 

  • Huang Y, Powers C, Moore V et al (2017) The PPAR pan-agonist bezafibrate ameliorates cardiomyopathy in a mouse model of Barth syndrome. Orphanet J Rare Dis 12:49

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ioannou N, Hargreaves IP, Allen G et al (2010) Bezafibrate induced increase in mitochondrial electron transport chain complex IV activity in human astrocytoma cells: implications for mitochondrial cytopathies and neurodegenerative diseases. Biofactors 36:468–473

    CAS  PubMed  Google Scholar 

  • Issac TG, Soundarya S, Christopher R et al (2015) Vitamin B12 deficiency: an important reversible co-morbidity in neuropsychiatric manifestations. Indian J Psychol Med 37:26–29

    PubMed  PubMed Central  Google Scholar 

  • Jakaria M, Azam S, Haque ME et al (2019) Taurine and its analogs in neurological disorders: focus on therapeutic potential and molecular mechanisms. Redox Biol 24:101223

    PubMed  PubMed Central  Google Scholar 

  • Jamilian H, Amirani E, Milajerdi A et al (2019) The effects of vitamin D supplementation on mental health, and biomarkers of inflammation and oxidative stress in patients with psychiatric disorders: a systematic review and meta-analysis of randomized controlled trials. Prog Neuro-Psychopharmacol Biol Psychiatry 94:109651

    CAS  Google Scholar 

  • Jardim FR, de Rossi FT, Nascimento MX et al (2018) Resveratrol and brain mitochondria: a review. Mol Neurobiol 55:2085–2101

    CAS  PubMed  Google Scholar 

  • Javadov S, Chapa-Dubocq X, Makarov V (2018) Different approaches to modeling analysis of mitochondrial swelling. Mitochondrion 38:58–70

    CAS  PubMed  Google Scholar 

  • Jensen JE, Daniels M, Haws C et al (2008) Triacetyluridine (TAU) decreases depressive symptoms and increases brain pH in bipolar patients. Exp Clin Psychopharmacol 16:199–206

    CAS  PubMed  Google Scholar 

  • Jia ZQ, Li SQ, Qiao WQ et al (2018) Ebselen protects mitochondrial function and oxidative stress while inhibiting the mitochondrial apoptosis pathway after acute spinal cord injury. Neurosci Lett 678:110–117

    CAS  PubMed  Google Scholar 

  • Jou MJ (2011) Melatonin preserves the transient mitochondrial permeability transition for protection during mitochondrial Ca(2+) stress in astrocyte. J Pineal Res 50:427–435

    CAS  PubMed  Google Scholar 

  • Juarez Olguin H, Calderon Guzman D, Hernandez Garcia E et al (2016) The role of dopamine and its dysfunction as a consequence of oxidative stress. Oxidative Med Cell Longev 2016:9730467

    Google Scholar 

  • Kannan K, Jain SK (2004) Effect of vitamin B6 on oxygen radicals, mitochondrial membrane potential, and lipid peroxidation in H2O2-treated U937 monocytes. Free Radic Biol Med 36:423–428

    CAS  PubMed  Google Scholar 

  • Kato T (2019) Current understanding of bipolar disorder: toward integration of biological basis and treatment strategies. Psychiatry Clin Neurosci 73:526–540

    PubMed  Google Scholar 

  • Kato T, Kato N (2000) Mitochondrial dysfunction in bipolar disorder. Bipolar Disord 2:180–190

    CAS  PubMed  Google Scholar 

  • Kato TM, Kubota-Sakashita M, Fujimori-Tonou N et al (2018) Ant1 mutant mice bridge the mitochondrial and serotonergic dysfunctions in bipolar disorder. Mol Psychiatry 23:2039–2049

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kim DJ, Lyoo IK, Yoon SJ et al (2007) Clinical response of quetiapine in rapid cycling manic bipolar patients and lactate level changes in proton magnetic resonance spectroscopy. Prog Neuro-Psychopharmacol Biol Psychiatry 31:1182–1188

    CAS  Google Scholar 

  • Kim HW, Rapoport SI, Rao JS (2010) Altered expression of apoptotic factors and synaptic markers in postmortem brain from bipolar disorder patients. Neurobiol Dis 37:596–603

    CAS  PubMed  Google Scholar 

  • Kim Y, Santos R, Gage FH et al (2017) Molecular mechanisms of bipolar disorder: progress made and future challenges. Front Cell Neurosci 11:30

    PubMed  PubMed Central  Google Scholar 

  • Kim Y, Vadodaria KC, Lenkei Z et al (2019) Mitochondria, metabolism, and redox mechanisms in psychiatric disorders. Antioxid Redox Signal 31:275–317

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kishi T, Nomura I, Sakuma K et al (2019) Melatonin receptor agonists-ramelteon and melatonin-for bipolar disorder: a systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials. Neuropsychiatr Dis Treat 15:1479–1486

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kocot J, Luchowska-Kocot D, Kielczykowska M et al (2017) Does vitamin C influence neurodegenerative diseases and psychiatric disorders? Nutrients 9:659

    PubMed Central  Google Scholar 

  • Kondo DG, Sung YH, Hellem TL et al (2011) Open-label uridine for treatment of depressed adolescents with bipolar disorder. J Child Adolesc Psychopharmacol 21:171–175

    PubMed  PubMed Central  Google Scholar 

  • Kontush K, Schekatolina S (2004) Vitamin E in neurodegenerative disorders: Alzheimer’s disease. Ann N Y Acad Sci 1031:249–262

    CAS  PubMed  Google Scholar 

  • Kovacs Z, D'Agostino DP, Diamond D et al (2019) Therapeutic potential of exogenous ketone supplement induced ketosis in the treatment of psychiatric disorders: review of current literature. Front Psych 10:363

    Google Scholar 

  • Kuang H, Duong A, Jeong H et al (2018) Lactate in bipolar disorder: a systematic review and meta-analysis. Psychiatry Clin Neurosci 72:546–555

    PubMed  Google Scholar 

  • Kubli DA, Gustafsson AB (2012) Mitochondria and mitophagy: the yin and yang of cell death control. Circ Res 111:1208–1221

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kumar P, Efstathopoulos P, Millischer V et al (2018) Mitochondrial DNA copy number is associated with psychosis severity and anti-psychotic treatment. Sci Rep 8:12743

    PubMed  PubMed Central  Google Scholar 

  • Kumari S, Mehta SL, Milledge GZ et al (2016) Ubisol-Q10 prevents glutamate-induced cell death by blocking mitochondrial fragmentation and permeability transition pore opening. Int J Biol Sci 12:688–700

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lagopoulos J, Hermens DF, Tobias-Webb J et al (2013) In vivo glutathione levels in young persons with bipolar disorder: a magnetic resonance spectroscopy study. J Psychiatr Res 47:412–417

    CAS  PubMed  Google Scholar 

  • Lange KW, Li S (2018) Resveratrol, pterostilbene, and dementia. Biofactors 44:83–90

    CAS  PubMed  Google Scholar 

  • Lee A, Hirabayashi Y, Kwon SK et al (2018) Emerging roles of mitochondria in synaptic transmission and neurodegeneration. Curr Opin Physiol 3:82–93

    PubMed  PubMed Central  Google Scholar 

  • Li XB, Gu JD, Zhou QH (2015) Review of aerobic glycolysis and its key enzymes – new targets for lung cancer therapy. Thorac Cancer 6:17–24

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liberti MV, Locasale JW (2016) The Warburg effect: how does it benefit cancer cells? Trends Biochem Sci 41:211–218

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liguori I, Russo G, Curcio F et al (2018) Oxidative stress, aging, and diseases. Clin Interv Aging 13:757–772

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lin DD, Crawford TO, Barker PB (2003) Proton MR spectroscopy in the diagnostic evaluation of suspected mitochondrial disease. AJNR Am J Neuroradiol 24:33–41

    PubMed  Google Scholar 

  • Loebl T, Raskin S (2013) A novel case report: acute manic psychotic episode after treatment with niacin. J Neuropsychiatry Clin Neurosci 25:E14

    PubMed  Google Scholar 

  • Lutz PE, Kieffer BL (2013) Opioid receptors: distinct roles in mood disorders. Trends Neurosci 36:195–206

    CAS  PubMed  Google Scholar 

  • Lyoo IK, Kong SW, Sung SM et al (2003) Multinuclear magnetic resonance spectroscopy of high-energy phosphate metabolites in human brain following oral supplementation of creatine-monohydrate. Psychiatry Res 123:87–100

    CAS  PubMed  Google Scholar 

  • MacDonald ML, Naydenov A, Chu M et al (2006) Decrease in creatine kinase messenger RNA expression in the hippocampus and dorsolateral prefrontal cortex in bipolar disorder. Bipolar Disord 8:255–264

    CAS  PubMed  PubMed Central  Google Scholar 

  • Machado-Vieira R, Pivovarova NB, Stanika RI et al (2011) The Bcl-2 gene polymorphism rs956572AA increases inositol 1,4,5-trisphosphate receptor-mediated endoplasmic reticulum calcium release in subjects with bipolar disorder. Biol Psychiatry 69:344–352

    CAS  PubMed  Google Scholar 

  • Maes M, Mihaylova I, Kubera M et al (2009) Lower plasma coenzyme Q10 in depression: a marker for treatment resistance and chronic fatigue in depression and a risk factor to cardiovascular disorder in that illness. Neuro Endocrinol Lett 30:462–469

    CAS  PubMed  Google Scholar 

  • Manfredi G, Kwong JQ, Oca-Cossio JA et al (2003) BCL-2 improves oxidative phosphorylation and modulates adenine nucleotide translocation in mitochondria of cells harboring mutant mtDNA. J Biol Chem 278:5639–5645

    CAS  PubMed  Google Scholar 

  • Mantle D, Hargreaves I (2019) Coenzyme Q10 and degenerative disorders affecting longevity: an overview. Antioxidants (Basel) 8:44

    CAS  Google Scholar 

  • Markham A, Bains R, Franklin P et al (2014) Changes in mitochondrial function are pivotal in neurodegenerative and psychiatric disorders: how important is BDNF? Br J Pharmacol 171:2206–2229

    CAS  PubMed  PubMed Central  Google Scholar 

  • Marsh WK, Penny JL, Rothschild AJ (2017) Vitamin D supplementation in bipolar depression: a double blind placebo controlled trial. J Psychiatr Res 95:48–53

    PubMed  Google Scholar 

  • Masaki C, Sharpley AL, Cooper CM et al (2016) Effects of the potential lithium-mimetic, ebselen, on impulsivity and emotional processing. Psychopharmacology 233:2655–2661

    CAS  PubMed  PubMed Central  Google Scholar 

  • Massaad CA, Klann E (2011) Reactive oxygen species in the regulation of synaptic plasticity and memory. Antioxid Redox Signal 14:2013–2054

    CAS  PubMed  PubMed Central  Google Scholar 

  • Matschke V, Theiss C, Matschke J (2019) Oxidative stress: the lowest common denominator of multiple diseases. Neural Regen Res 14:238–241

    PubMed  PubMed Central  Google Scholar 

  • McCann RF, Ross DA (2018) So happy together: the storied marriage between mitochondria and the mind. Biol Psychiatry 83:e47–e49

    PubMed  PubMed Central  Google Scholar 

  • McCarthy MJ, Le Roux MJ, Wei H et al (2016) Calcium channel genes associated with bipolar disorder modulate lithium's amplification of circadian rhythms. Neuropharmacology 101:439–448

    CAS  PubMed  Google Scholar 

  • Mehrpooya M, Yasrebifar F, Haghighi M et al (2018) Evaluating the effect of coenzyme Q10 augmentation on treatment of bipolar depression: a double-blind controlled clinical trial. J Clin Psychopharmacol 38:460–466

    CAS  PubMed  Google Scholar 

  • Mertens J, Wang QW, Kim Y et al (2015) Differential responses to lithium in hyperexcitable neurons from patients with bipolar disorder. Nature 527:95–99

    CAS  PubMed  PubMed Central  Google Scholar 

  • Minocycline for Bipolar Depression (2012). https://clinicaltrials.gov/ct2/show/NCT01514422

  • Modica-Napolitano JS, Renshaw PF (2004) Ethanolamine and phosphoethanolamine inhibit mitochondrial function in vitro: implications for mitochondrial dysfunction hypothesis in depression and bipolar disorder. Biol Psychiatry 55:273–277

    CAS  PubMed  Google Scholar 

  • Moffett JR, Arun P, Ariyannur PS et al (2013) N-Acetylaspartate reductions in brain injury: impact on post-injury neuroenergetics, lipid synthesis, and protein acetylation. Front Neuroenerg 5:11

    CAS  Google Scholar 

  • Monzani E, Nicolis S, Dell'Acqua S et al (2019) Dopamine, oxidative stress and protein-quinone modifications in Parkinson's and other neurodegenerative diseases. Angew Chem Int Ed Engl 58:6512–6527

    CAS  PubMed  Google Scholar 

  • Moore A, Beidler J, Hong MY (2018) Resveratrol and depression in animal models: a systematic review of the biological mechanisms. Molecules 23:2197

    PubMed Central  Google Scholar 

  • Morris G, Anderson G, Berk M et al (2013) Coenzyme Q10 depletion in medical and neuropsychiatric disorders: potential repercussions and therapeutic implications. Mol Neurobiol 48:883–903

    CAS  PubMed  Google Scholar 

  • Morris G, Walder K, McGee SL et al (2017) A model of the mitochondrial basis of bipolar disorder. Neurosci Biobehav Rev 74:1–20

    CAS  PubMed  Google Scholar 

  • Murphy AN, Bredesen DE, Cortopassi G et al (1996) Bcl-2 potentiates the maximal calcium uptake capacity of neural cell mitochondria. Proc Natl Acad Sci U S A 93:9893–9898

    CAS  PubMed  PubMed Central  Google Scholar 

  • Murphy BL, Stoll AL, Harris PQ et al (2012) Omega-3 fatty acid treatment, with or without cytidine, fails to show therapeutic properties in bipolar disorder: a double-blind, randomized add-on clinical trial. J Clin Psychopharmacol 32:699–703

    CAS  PubMed  Google Scholar 

  • Nascimento C, Kim HK, Young LT et al (2015) Glutathione-mediated effects of lithium in decreasing protein oxidation induced by mitochondrial complex I dysfunction. J Neural Transm (Vienna) 122:741–746

    CAS  Google Scholar 

  • Naydenov AV, MacDonald ML, Ongur D et al (2007) Differences in lymphocyte electron transport gene expression levels between subjects with bipolar disorder and normal controls in response to glucose deprivation stress. Arch Gen Psychiatry 64:555–564

    PubMed  Google Scholar 

  • Naziroglu M, Cig B, Ozgul C (2013) Neuroprotection induced by N-acetylcysteine against cytosolic glutathione depletion-induced Ca2+ influx in dorsal root ganglion neurons of mice: role of TRPV1 channels. Neuroscience 242:151–160

    CAS  PubMed  Google Scholar 

  • Neergheen V, Chalasani A, Wainwright L, Yubero D, Montero R, Artuch R, Hargreaves I (2017) Coenzyme Q10 in the treatment of mitochondrial disease. J Inborn Errors Metabol Screen 5

    Google Scholar 

  • Ngamchuea K, Batchelor-McAuley C, Williams C et al (2018) Salivary glutathione in bipolar disorder: a pilot study. J Affect Disord 238:277–280

    CAS  PubMed  Google Scholar 

  • Nierenberg AA, Kansky C, Brennan BP et al (2013) Mitochondrial modulators for bipolar disorder: a pathophysiologically informed paradigm for new drug development. Aust N Z J Psychiatry 47:26–42

    PubMed  Google Scholar 

  • Novakova M, Prasko J, Latalova K et al (2015) The circadian system of patients with bipolar disorder differs in episodes of mania and depression. Bipolar Disord 17:303–314

    CAS  PubMed  Google Scholar 

  • Odeya D, Galila A, Lilah T (2018) The observed alteration in BCL2 expression following lithium treatment is influenced by the choice of normalization method. Sci Rep 8:6399

    PubMed  PubMed Central  Google Scholar 

  • Okereke OI, Cook NR, Albert CM et al (2015) Effect of long-term supplementation with folic acid and B vitamins on risk of depression in older women. Br J Psychiatry 206:324–331

    PubMed  PubMed Central  Google Scholar 

  • Onukwufor JO, Berry BJ, Wojtovich AP (2019) Physiologic implications of reactive oxygen species production by mitochondrial complex I reverse electron transport. Antioxidants (Basel) 8:285

    CAS  Google Scholar 

  • Orrenius S (2004) Mitochondrial regulation of apoptotic cell death. Toxicol Lett 149:19–23

    CAS  PubMed  Google Scholar 

  • Ozkul A, Sair A, Akyol A et al (2014) Effects of lithium and lamotrigine on oxidative-nitrosative stress and spatial learning deficit after global cerebral ischemia. Neurochem Res 39:853–861

    CAS  PubMed  Google Scholar 

  • Papakostas GI, Mischoulon D, Shyu I et al (2010) S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. Am J Psychiatry 167:942–948

    PubMed  Google Scholar 

  • Pattij T, Vanderschuren LJ (2008) The neuropharmacology of impulsive behaviour. Trends Pharmacol Sci 29:192–199

    CAS  PubMed  Google Scholar 

  • Pehlivan FE (2017) Vitamin C: an antioxidant agent. Vitamin C. https://doi.org/10.5772/intechopen.69660

  • Pei L, Wallace DC (2018) Mitochondrial etiology of neuropsychiatric disorders. Biol Psychiatry 83:722–730

    CAS  PubMed  Google Scholar 

  • Pereira C, Chavarria V, Vian J et al (2018) Mitochondrial agents for bipolar disorder. Int J Neuropsychopharmacol 21:550–569

    CAS  PubMed  PubMed Central  Google Scholar 

  • Peters A, Schweiger U, Pellerin L et al (2004) The selfish brain: competition for energy resources. Neurosci Biobehav Rev 28:143–180

    CAS  PubMed  Google Scholar 

  • Petrov B, Aldoori A, James C et al (2018) Bipolar disorder in youth is associated with increased levels of vitamin D-binding protein. Transl Psychiatry 8:61

    PubMed  PubMed Central  Google Scholar 

  • Pham-Huy LA, He H, Pham-Huy C (2008) Free radicals, antioxidants in disease and health. Int J Biomed Sci 4:89–96

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pizzino G, Irrera N, Cucinotta M et al (2017) Oxidative stress: harms and benefits for human health. Oxidative Med Cell Longev 2017:8416763

    Google Scholar 

  • Pullar JM, Carr AC, Bozonet SM et al (2018) High vitamin C status is associated with elevated mood in male tertiary students. Antioxidants (Basel) 7:91

    Google Scholar 

  • Raha S, Robinson BH (2000) Mitochondria, oxygen free radicals, disease and ageing. Trends Biochem Sci 25:502–508

    CAS  PubMed  Google Scholar 

  • Reiter RJ, Rosales-Corral S, Tan DX et al (2017) Melatonin as a mitochondria-targeted antioxidant: one of evolution's best ideas. Cell Mol Life Sci 74:3863–3881

    CAS  PubMed  Google Scholar 

  • Rex A, Schickert R, Fink H (2004) Antidepressant-like effect of nicotinamide adenine dinucleotide in the forced swim test in rats. Pharmacol Biochem Behav 77:303–307

    CAS  PubMed  Google Scholar 

  • Ricca C, Aillon A, Bergandi L et al (2018) Vitamin D receptor is necessary for mitochondrial function and cell health. Int J Mol Sci 19:1672

    PubMed Central  Google Scholar 

  • Rizvi S, Raza ST, Ahmed F et al (2014) The role of vitamin e in human health and some diseases. Sultan Qaboos Univ Med J 14:e157–e165

    PubMed  PubMed Central  Google Scholar 

  • Robertson OD, Coronado NG, Sethi R et al (2019) Putative neuroprotective pharmacotherapies to target the staged progression of mental illness. Early Interv Psychiatry 13:1032–1049

    PubMed  Google Scholar 

  • Roitman S, Green T, Osher Y et al (2007) Creatine monohydrate in resistant depression: a preliminary study. Bipolar Disord 9:754–758

    CAS  PubMed  Google Scholar 

  • Rosa AR, Singh N, Whitaker E et al (2014) Altered plasma glutathione levels in bipolar disorder indicates higher oxidative stress; a possible risk factor for illness onset despite normal brain-derived neurotrophic factor (BDNF) levels. Psychol Med 44:2409–2418

    CAS  PubMed  Google Scholar 

  • Ross S, Bossis A, Guss J et al (2016) Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol 30:1165–1180

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sabir MS, Haussler MR, Mallick S et al (2018) Optimal vitamin D spurs serotonin: 1,25-dihydroxyvitamin D represses serotonin reuptake transport (SERT) and degradation (MAO-A) gene expression in cultured rat serotonergic neuronal cell lines. Genes Nutr 13:19

    PubMed  PubMed Central  Google Scholar 

  • Sahlin K, Harris RC (2011) The creatine kinase reaction: a simple reaction with functional complexity. Amino Acids 40:1363–1367

    CAS  PubMed  Google Scholar 

  • Sahraian A, Ghanizadeh A, Kazemeini F (2015) Vitamin C as an adjuvant for treating major depressive disorder and suicidal behavior, a randomized placebo-controlled clinical trial. Trials 16:94

    PubMed  PubMed Central  Google Scholar 

  • Samuni Y, Goldstein S, Dean OM et al (2013) The chemistry and biological activities of N-acetylcysteine. Biochim Biophys Acta 1830:4117–4129

    CAS  PubMed  Google Scholar 

  • Sanoobar M, Eghtesadi S, Azimi A et al (2015) Coenzyme Q10 supplementation ameliorates inflammatory markers in patients with multiple sclerosis: a double blind, placebo, controlled randomized clinical trial. Nutr Neurosci 18:169–176

    CAS  PubMed  Google Scholar 

  • Sarris J, Papakostas GI, Vitolo O et al (2014) S-adenosyl methionine (SAMe) versus escitalopram and placebo in major depression RCT: efficacy and effects of histamine and carnitine as moderators of response. J Affect Disord 164:76–81

    CAS  PubMed  Google Scholar 

  • Sarris J, Price LH, Carpenter LL et al (2015) Is S-adenosyl methionine (SAMe) for depression only effective in males? A re-analysis of data from a randomized clinical trial. Pharmacopsychiatry 48:141–144

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sarris J, Byrne GJ, Bousman C et al (2018) Adjunctive S-adenosylmethionine (SAMe) in treating non-remittent major depressive disorder: an 8-week double-blind, randomized, controlled trial. Eur Neuropsychopharmacol 28:1126–1136

    CAS  PubMed  Google Scholar 

  • Sarris J, Byrne GJ, Stough C et al (2019) Nutraceuticals for major depressive disorder- more is not merrier: an 8-week double-blind, randomised, controlled trial. J Affect Disord 245:1007–1015

    PubMed  Google Scholar 

  • Scaini G, Barichello T, Fries GR et al (2019) TSPO upregulation in bipolar disorder and concomitant downregulation of mitophagic proteins and NLRP3 inflammasome activation. Neuropsychopharmacology 44:1291–1299

    CAS  PubMed  Google Scholar 

  • Sena LA, Chandel NS (2012) Physiological roles of mitochondrial reactive oxygen species. Mol Cell 48:158–167

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sharpley AL, Hockney R, McPeake L et al (2014) Folic acid supplementation for prevention of mood disorders in young people at familial risk: a randomised, double blind, placebo controlled trial. J Affect Disord 167:306–311

    CAS  PubMed  Google Scholar 

  • Shults CW, Oakes D, Kieburtz K et al (2002) Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol 59:1541–1550

    PubMed  Google Scholar 

  • Shultz RB, Zhong Y (2017) Minocycline targets multiple secondary injury mechanisms in traumatic spinal cord injury. Neural Regen Res 12:702–713

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sigitova E, Fisar Z, Hroudova J et al (2017) Biological hypotheses and biomarkers of bipolar disorder. Psychiatry Clin Neurosci 71:77–103

    PubMed  Google Scholar 

  • Sikoglu EM, Navarro AA, Starr D et al (2015) Vitamin D3 supplemental treatment for mania in youth with bipolar spectrum disorders. J Child Adolesc Psychopharmacol 25:415–424

    CAS  PubMed  PubMed Central  Google Scholar 

  • Simon J, Geddes JR, Gardiner A et al (2018) Comparative economic evaluation of quetiapine plus lamotrigine combination vs quetiapine monotherapy (and folic acid vs placebo) in patients with bipolar depression (CEQUEL). Bipolar Disord 20:733–745

    CAS  PubMed  PubMed Central  Google Scholar 

  • Siwek M, Sowa-Kucma M, Styczen K et al (2016) Thiobarbituric acid-reactive substances: markers of an acute episode and a late stage of bipolar disorder. Neuropsychobiology 73:116–122

    CAS  PubMed  Google Scholar 

  • Slusarczyk W, Olakowska E, Larysz-Brysz M et al (2019) Use of ebselen as a neuroprotective agent in rat spinal cord subjected to traumatic injury. Neural Regen Res 14:1255–1261

    PubMed  PubMed Central  Google Scholar 

  • Soeiro-de-Souza MG, Pastorello BF, Leite Cda C et al (2016) Dorsal anterior cingulate lactate and glutathione levels in euthymic bipolar I disorder: 1H-MRS study. Int J Neuropsychopharmacol 19:pyw032

    PubMed  PubMed Central  Google Scholar 

  • Soeiro-de-Souza MG, Otaduy MCG, Machado-Vieira R et al (2018a) Anterior cingulate cortex glutamatergic metabolites and mood stabilizers in euthymic bipolar I disorder patients: a proton magnetic resonance spectroscopy study. Biol Psychiatry Cogn Neurosci Neuroimaging 3:985–991

    PubMed  Google Scholar 

  • Soeiro-de-Souza MG, Otaduy MCG, Machado-Vieira R et al (2018b) Lithium-associated anterior cingulate neurometabolic profile in euthymic bipolar I disorder: a (1)H-MRS study. J Affect Disord 241:192–199

    CAS  PubMed  Google Scholar 

  • Srivastava R, Faust T, Ramos A et al (2018) Dynamic changes of the mitochondria in psychiatric illnesses: new mechanistic insights from human neuronal models. Biol Psychiatry 83:751–760

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stacey D, Schubert KO, Clark SR et al (2018) A gene co-expression module implicating the mitochondrial electron transport chain is associated with long-term response to lithium treatment in bipolar affective disorder. Transl Psychiatry 8:183

    PubMed  PubMed Central  Google Scholar 

  • Steckert AV, Valvassori SS, Moretti M et al (2010) Role of oxidative stress in the pathophysiology of bipolar disorder. Neurochem Res 35:1295–1301

    CAS  PubMed  Google Scholar 

  • Stern S, Santos R, Marchetto MC et al (2018) Neurons derived from patients with bipolar disorder divide into intrinsically different sub-populations of neurons, predicting the patients' responsiveness to lithium. Mol Psychiatry 23:1453–1465

    CAS  PubMed  Google Scholar 

  • Szczepankiewicz A (2013) Evidence for single nucleotide polymorphisms and their association with bipolar disorder. Neuropsychiatr Dis Treat 9:1573–1582

    PubMed  PubMed Central  Google Scholar 

  • Tardiolo G, Bramanti P, Mazzon E (2018) Overview on the effects of N-acetylcysteine in neurodegenerative diseases. Molecules 23:3305

    PubMed Central  Google Scholar 

  • Taurine as an Anti-Manic Agent: A Double-Blind, Placebo-Controlled Study (2005). https://clinicaltrials.gov/ct2/show/NCT00217165

  • Toniolo RA, Silva M, Fernandes FBF et al (2018) A randomized, double-blind, placebo-controlled, proof-of-concept trial of creatine monohydrate as adjunctive treatment for bipolar depression. J Neural Transm (Vienna) 125:247–257

    CAS  Google Scholar 

  • Traina G (2016) The neurobiology of acetyl-L-carnitine. Front Biosci (Landmark Ed) 21:1314–1329

    CAS  Google Scholar 

  • Tsai MC, Huang TL (2015) Thiobarbituric acid reactive substances (TBARS) is a state biomarker of oxidative stress in bipolar patients in a manic phase. J Affect Disord 173:22–26

    CAS  PubMed  Google Scholar 

  • Vaarmann A, Kovac S, Holmstrom KM et al (2013) Dopamine protects neurons against glutamate-induced excitotoxicity. Cell Death Dis 4:e455

    CAS  PubMed  PubMed Central  Google Scholar 

  • Valvassori SS, Rezin GT, Ferreira CL et al (2010) Effects of mood stabilizers on mitochondrial respiratory chain activity in brain of rats treated with d-amphetamine. J Psychiatr Res 44:903–909

    PubMed  Google Scholar 

  • Valvassori SS, Bavaresco DV, Feier G et al (2018) Increased oxidative stress in the mitochondria isolated from lymphocytes of bipolar disorder patients during depressive episodes. Psychiatry Res 264:192–201

    CAS  PubMed  Google Scholar 

  • van Enkhuizen J, Janowsky DS, Olivier B et al (2015) The catecholaminergic-cholinergic balance hypothesis of bipolar disorder revisited. Eur J Pharmacol 753:114–126

    PubMed  Google Scholar 

  • Vellekkatt F, Menon V (2019) Efficacy of vitamin D supplementation in major depression: a meta-analysis of randomized controlled trials. J Postgrad Med 65:74–80

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang D, Li Z, Liu W et al (2018) Differential mitochondrial DNA copy number in three mood states of bipolar disorder. BMC Psychiatry 18:149

    PubMed  PubMed Central  Google Scholar 

  • Weber WA, Dudley J, Lee JH et al (2013) A pilot study of alterations in high energy phosphoryl compounds and intracellular pH in unmedicated adolescents with bipolar disorder. J Affect Disord 150:1109–1113

    CAS  PubMed  Google Scholar 

  • Wilson C, Lee MD, Heathcote HR et al (2019) Mitochondrial ATP production provides long-range control of endothelial inositol trisphosphate-evoked calcium signaling. J Biol Chem 294:737–758

    CAS  PubMed  Google Scholar 

  • Wu GF, Ren S, Tang RY et al (2017) Antidepressant effect of taurine in chronic unpredictable mild stress-induced depressive rats. Sci Rep 7:4989

    PubMed  PubMed Central  Google Scholar 

  • Wurtman RJ, Regan M, Ulus I et al (2000) Effect of oral CDP-choline on plasma choline and uridine levels in humans. Biochem Pharmacol 60:989–992

    CAS  PubMed  Google Scholar 

  • Yamaki N, Otsuka I, Numata S et al (2018) Mitochondrial DNA copy number of peripheral blood in bipolar disorder: the present study and a meta-analysis. Psychiatry Res 269:115–117

    CAS  PubMed  Google Scholar 

  • Yang L, Ran Y, Quan Z et al (2019) Pterostilbene, an active component of the dragon's blood extract, acts as an antidepressant in adult rats. Psychopharmacology 236:1323–1333

    CAS  PubMed  Google Scholar 

  • Yoon SJ, Lyoo IK, Haws C et al (2009) Decreased glutamate/glutamine levels may mediate cytidine's efficacy in treating bipolar depression: a longitudinal proton magnetic resonance spectroscopy study. Neuropsychopharmacology 34:1810–1818

    CAS  PubMed  Google Scholar 

  • Yu W, Greenberg ML (2016) Inositol depletion, GSK3 inhibition and bipolar disorder. Future Neurol 11:135–148

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yuksel C, Du F, Ravichandran C et al (2015) Abnormal high-energy phosphate molecule metabolism during regional brain activation in patients with bipolar disorder. Mol Psychiatry 20:1079–1084

    CAS  PubMed  Google Scholar 

  • Zhang J, Wang X, Vikash V et al (2016) ROS and ROS-mediated cellular signaling. Oxidative Med Cell Longev 2016:4350965

    Google Scholar 

  • Zheng W, Zhu XM, Zhang QE et al (2019) Adjunctive minocycline for major mental disorders: a systematic review. J Psychopharmacol 33:1215–1226

    CAS  PubMed  Google Scholar 

  • Zverova M, Hroudova J, Fisar Z et al (2019) Disturbances of mitochondrial parameters to distinguish patients with depressive episode of bipolar disorder and major depressive disorder. Neuropsychiatr Dis Treat 15:233–240

    CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Beer Yaakov-Ness Ziona Mental Health Center, Tel Aviv University, Tel-Aviv, Israel

    Maya Kuperberg

  2. Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA

    Sophie L. A. Greenebaum & Andrew A. Nierenberg

  3. Harvard Medical School, Boston, MA, USA

    Andrew A. Nierenberg

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  1. Maya Kuperberg
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  2. Sophie L. A. Greenebaum
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  3. Andrew A. Nierenberg
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Correspondence to Sophie L. A. Greenebaum .

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  1. PO72 De Crespigny Park, King’s College London, London, UK

    Allan H. Young

  2. PO72 De Crespigny Park, King’s College London, London, UK

    Mario F. Juruena

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Kuperberg, M., Greenebaum, S.L.A., Nierenberg, A.A. (2020). Targeting Mitochondrial Dysfunction for Bipolar Disorder. In: Young, A.H., Juruena, M.F. (eds) Bipolar Disorder: From Neuroscience to Treatment. Current Topics in Behavioral Neurosciences, vol 48. Springer, Cham. https://doi.org/10.1007/7854_2020_152

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