Blood metabolomics analysis identifies abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism in bipolar disorder

BBA Clinical

Volumn 5, Issue , 2016, Pages 151-158

  Yoshimi, Noriko ^a,b   Futamura, Takashi ^b   Kakumoto, Keiji ^b   Salehi, Alireza M ^c   Sellgren, Carl M ^d,e   Holmén Larsson, Jessica ^f   Jakobsson, Joel ^f   Pålsson, Erik ^f   Landén, Mikael ^f,g   Hashimoto, Kenji ^a  

^a CHIBA UNIVERSITY   (Japan)

^b OTSUKA PHARMACEUTICAL CO LTD   (Japan)

^c KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^d MASSACHUSETTS GENERAL HOSPITAL   (United States)

^e BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^f UNIVERSITY OF GOTHENBURG   (Sweden)

^g KAROLINSKA INSTITUTE   (Sweden)

Author keywords

Arginine; Bipolar disorder; N acetylglutamic acid; Pyruvate; Serine; alanine

Indexed keywords

2 OXOGLUTARIC ACID; ANTICONVULSIVE AGENT; ANTIDEPRESSANT AGENT; ANXIOLYTIC AGENT; ARGININE; BETA ALANINE; BETAINE; CITRIC ACID; CREATINE; CREATINE PHOSPHATE; FUMARIC ACID; LAMOTRIGINE; LITHIUM; MOOD STABILIZER; N ACETYLGLUTAMIC ACID; NEUROLEPTIC AGENT; PYRUVIC ACID; SERINE; THREONINE; TRYPTOPHAN; VALPROIC ACID;

ADULT; AMINO ACID METABOLISM; ANIMAL EXPERIMENT; ARTICLE; BIPOLAR DISORDER; BLOOD ANALYSIS; CITRIC ACID CYCLE; CLINICAL GLOBAL IMPRESSION SCALE; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; GLOBAL ASSESSMENT OF FUNCTIONING; HUMAN; MAJOR CLINICAL STUDY; MALE; METABOLOMICS; NONHUMAN; PRIORITY JOURNAL; RAT; TANDEM MASS SPECTROMETRY; TIME OF FLIGHT MASS SPECTROMETRY; UREA CYCLE;

EID: 84977111858     PISSN: 22146474     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bbacli.2016.03.008     Document Type: Article

References (67)

1. Merikangas K.R., Jin R., He J.P., Kessler R.C., Lee S., Sampson N.A., Viana M.C., Andrade L.H., Hu C., Karam E.G., Ladea M., Medina-Mora M.E., Ono Y., Posada-Villa J., Sagar R., Wells J.E., Zarkov Z. Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Arch. Gen. Psychiatry 2011, 68:241-251.
2. Hirschfeld R.M., Cass A.R., Holt D.C., Carlson C.A. Screening for bipolar disorder in patients treated for depression in a family medicine clinic. J. Am. Board Fam. Pract. 2005, 18:233-239.
3. Viktorin A., Lichtenstein P., Thase M.E., Larsson H., Lundholm C., Magnusson P.K., Landén M. The risk of switch to mania in patients with bipolar disorder during treatment with an antidepressant alone and in combination with a mood stabilizer. Am. J. Psychiatry 2014, 171:1067-1073.
4. Altshuler L.L., Post R.M., Leverich G.S., Mikalauskas K., Rosoff A., Ackerman L. Antidepressant-induced mania and cycle acceleration: a controversy revisited. Am. J. Psychiatry 1995, 152:1130-1138.
5. Hirschfeld R.M. Differential diagnosis of bipolar disorder and major depressive disorder. J. Affect. Disord. 2014, 169(Suppl. 1):S12-S16.
6. Goodwin G.M. Evidence-based guidelines for treating bipolar disorder: revised second edition-recommendations from the British Association for Psychopharmacology. J. Psychopharmacol. 2009, 23:346-388.
7. Yatham L.N., Kennedy S.H., Parikh S.V., Schaffer A., Beaulieu S., Alda M., O'Donovan C., Macqueen G., McIntyre R.S., Sharma V., Ravindran A., Young L.T., Milev R., Bond D.J., Frey B.N., Goldstein B.I., Lafer B., Birmaher B., Ha K., Nolen W.A., Berk M. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013. Bipolar Disord. 2013, 15:1-44.
8. Isgren A., Jakobsson J., Pålsson E., Ekman C.J., Johansson A.G., Sellgren C., Blennow K., Zetterberg H., Landén M. Increased cerebrospinal fluid interleukin-8 in bipolar disorder patients associated with lithium and antipsychotic treatment. Brain Behav. Immun. 2015, 43:198-204.
9. Jakobsson J., Bjerke M., Sahebi S., Isgren A., Ekman C.J., Sellgren C., Olsson B., Zetterberg H., Blennow K., Pålsson E., Landén M. Monocyte and microglial activation in patients with mood-stabilized bipolar disorder. J. Psychiatry Neurosci. 2015, 40:250-258.
10. Sellgren C.M., Kegel M.E., Bergen S.E., Ekman C.J., Olsson S., Larsson M., Vawter M.P., Backlund L., Sullivan P.F., Sklar P., Smoller J.W., Magnusson P.K., Hultman C.M., Walther-Jallow L., Svensson C.I., Lichtenstein P., Schalling M., Engberg G., Erhardt S., Landén M. A genome-wide association study of kynurenic acid in cerebrospinal fluid: implications for psychosis and cognitive impairment in bipolar disorder. Mol. Psychiatry 2015, Dec 15. doi: 10.1038/mp.2015.186.
11. Kato T., Kato N. Mitochondrial dysfunction in bipolar disorder. Bipolar Disord. 2000, 2:180-190.
12. Iwamoto K., Bundo M., Kato T. Altered expression of mitochondria-related genes in postmortem brains of patients with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray analysis. Hum. Mol. Genet. 2005, 14:241-253.
13. Kato T. Molecular neurobiology of bipolar disorder: a disease of 'mood-stabilizing neurons'?. Trends Neurosci. 2008, 31:495-503.
14. Quiroz J.A., Gray N.A., Kato T., Manji H.K. Mitochondrially mediated plasticity in the pathophysiology and treatment of bipolar disorder. Neuropsychopharmacology 2008, 33:2551-2565.
15. Konradi C., Sillivan S.E., Clay H.B. Mitochondria, oligodendrocytes and inflammation in bipolar disorder: evidence from transcriptome studies points to intriguing parallels with multiple sclerosis. Neurobiol. Dis. 2012, 45:37-47.
16. Frey B.N., Andreazza A.C., Houenou J., Jamain S., Goldstein B.I., Frye M.A., Leboyer M., Berk M., Malhi G.S., Lopez-Jaramillo C., Taylor V.H., Dodd S., Frangou S., Hall G.B., Fernandes B.S., Kauer-Sant'Anna M., Yatham L.N., Kapczinski F., Young L.T. Biomarkers in bipolar disorder: a positional paper from the International Society for Bipolar Disorders Biomarkers Task Force. Aust. N. Z. J. Psychiatry 2013, 47:321-332.
17. Goldstein B.I., Young L.T. Toward clinically applicable biomarkers in bipolar disorder: focus on BDNF, inflammatory markers, and endothelial function. Curr. Psychiatry Rep. 2015, 15:425.
18. de Sousa R.T., Machado-Vieira R., Zarate C.A., Manji H.K. Targeting mitochondrially mediated plasticity to develop improved therapeutics for bipolar disorder. Expert Opin. Ther. Targets 2014, 18:1131-1147.
19. Rolstad S., Jakobsson J., Sellgren C., Isgren A., Ekman C.J., Bjerke M., Blennow K., Zetterberg H., Pålsson E., Landén M. CSF neuroinflammatory biomarkers in bipolar disorder are associated with cognitive impairment. Eur. Neuropsychopharmacol. 2015, 25:1091-1098.
20. Hashimoto K. Brain-derived neurotrophic factor as a biomarker for mood disorders: an historical overview and future directions. Psychiatry Clin. Neurosci. 2010, 64:341-357.
21. Södersten K., Pålsson E., Ishima T., Funa K., Landén M., Hashimoto K., Ågren H. Abnormality in serum levels of mature brain-derived neurotrophic factor (BDNF) and its precursor proBDNF in mood-stabilized patients with bipolar disorder: a study of two independent cohorts. J. Affect. Disord. 2014, 160:1-9.
22. Li Z., Zhang C., Fan J., Yuan C., Huang J., Chen J., Yi Z., Wang Z., Hong W., Wang Y., Lu W., Guan Y., Wu Z., Su Y., Cao L., Hu Y., Hao Y., Liu M., Yu S., Cui D., Xu L., Song Y., Fang Y. Brain-derived neurotrophic factor levels and bipolar disorder in patients in their first depressive episode: 3-year prospective longitudinal study. Br. J. Psychiatry 2014, 205:29-35.
23. Hashimoto K. BDNF and proBDNF as biomarkers for bipolar disorder. Br. J. Psychiatry 2014, 205:410.
24. Hashimoto K. Brain-derived neurotrophic factor (BDNF) and its precursor proBDNF as diagnostic biomarkers for major depressive disorder and bipolar disorder. Eur. Arch. Psychiatry Clin. Neurosci. 2015, 265:83-84.
25. Munkholm K., Vinberg M., Kessing L.V. Peripheral blood brain-derived neurotrophic factor in bipolar disorder: a comprehensive systematic review and meta-analysis. Mol. Psychiatry 2016, 21:216-228.
26. Pålsson E., Jakobsson J., Södersten K., Fujita Y., Sellgren C., Ekman C.J., Ågren H., Hashimoto K., Landén M. Markers of glutamate signaling in cerebrospinal fluid and serum from patients with bipolar disorder and healthy controls. Eur. Neuropsychopharmacol. 2015, 25:133-140.
27. Holmes E., Wilson I.D., Nicholson J.K. Metabolic phenotyping in health and disease. Cell 2008, 134:714-717.
28. Quinones M.P., Kaddurah-Daouk R,. Metabolomics tools for identifying biomarkers for neuropsychiatric diseases. Neurobiol. Dis. 2009, 35:165-176.
29. Davies S.K., Ang J.E., Revell V.L., Holmes B., Mann A., Robertson F.P., Cui N., Middleton B., Ackermann K., Kayser M., Thumser A.E., Raynaud F.I., Skene D.J. Effect of sleep deprivation on the human metabolome. Proc. Natl. Acad. Sci. U. S. A. 2014, 111:10761-10766.
30. Soga T., Igarashi K., Ito C., Mizobuchi K., Zimmermann H.P., Tomita M. Metabolomic profiling of anionic metabolites by capillary electrophoresis mass spectrometry. Anal. Chem. 2009, 81:6165-6174.
31. Yoshimi N., Futamura T., Bergen S.E., Iwayama Y., Ishima T., Sellgren C., Ekman C.J., Jakobsson J., Pålsson E., Kakumoto K., Ohgi Y., Yoshikawa T., Landén M., Hashimoto K. Cerebrospinal fluid metabolomics identifies a key role of isocitrate dehydrogenase in bipolar disorder: evidence in support of mitochondrial dysfunction hypothesis. Mol. Psychiatry Jan 19 2016, doi: 10.1038/mp.2015.217.
32. Koike S., Bundo M., Iwamoto K., Suga M., Kuwabara H., Ohashi Y., Shinoda K., Takano Y., Iwashiro N., Satomura Y., Nagai T., Natsubori T., Tada M., Yamasue H., Kasai K. A snapshot of plasma metabolites in first-episode schizophrenia: a capillary electrophoresis time-of-flight mass spectrometry study. Translat. Psychiatry 2014, 4.
33. Kuwabara H., Yamasue H., Koike S., Inoue H., Kawakubo Y., Kuroda M., Iwashiro Y.N., Natsubori T., Aoki Y., Kano Y., Kasai K. Altered metabolites in the plasma of autism spectrum disorder: a capillary electrophoresis time-of-flight mass spectroscopy study. PloS One 2013, (8):e73814.
34. Ryden E., Johansson C., Blennow K., Landén M. Lower CSF HVA and 5-HIAA in bipolar disorder type 1 with a history of childhood ADHD. J. Neural Transm. 2009, 116:1667-1674.
35. Jakobsson J., Bjerke M., Ekman C.J., Sellgren C., Johansson A.G., Zetterberg H., Blennow K., Landén M. Elevated concentrations of neurofilament light chain in the cerebrospinal fluid of bipolar disorder patients. Neuropsychopharmacology 2014, 39:2349-2356.
36. Sachs G.S., Thase M.E., Otto M.W., Bauer M., Miklowitz D., Wisniewski S.R., Lavori P., Lebowitz B., Rudorfer M., Frank E., Nierenberg A.A., Fava M., Bowden C., Ketter T., Marangell L., Calabrese J., Kupfer D., Rosenbaum J.F. Rationale, design, and methods of the systematic treatment enhancement program for bipolar disorder (STEP-BD). Biol. Psychiatry 2003, 53:1028-1042.
37. Sheehan D.V., Lecrubier Y., Sheehan K.H., Amorim P., Janavs J., Weiller E., Hergueta T., Baker R., Dunbar G.C. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J. Clin. Psychiatry 1998, 59(Suppl. 20):22-33.
38. Saunders J.B., Aasland O.G., Babor T.F., de la Fuente J.R., Grant M. Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption-II. Addiction 1993, 88:791-804.
39. Soga T., Heiger D.N. Amino acid analysis by capillary electrophoresis electrospray ionization mass spectrometry. Anal. Chem. 2000, 72:1236-1241.
40. Soga T., Ohashi Y., Ueno Y., Naraoka H., Tomita M., Nishioka T. Quantitative metabolome analysis using capillary electrophoresis mass spectrometry. J. Proteome Res. 2003, 2:488-494.
41. Sugimoto M., Wong D.T., Hirayama A., Soga T., Tomita M. Capillary electrophoresis mass spectrometry-based saliva metabolomics identified oral, breast and pancreatic cancer-specific profiles. Metabolomics 2010, 6:78-95.
42. Allen D.M. The relationship between variable selection and data augmentation, and a method for prediction. Technometrics 1974, 16:125-127.
43. Miller A.J. Subset selection in regression, Chapman and Hall/CRC 1974.
44. Hunziker S., Bivens M.J., Cocchi M.N., Miller J., Salciccioli J., Howell M.D., Donnino M.M. International validation of the out-of-hospital cardiac arrest score in the United States. Crit. Care Med. 2011, 39:1670-1674.
45. Wadelius M., Chen L.Y., Lindh J.D., Eriksson N., Ghori M.J., Bumpstead S., Holm L., McGinnis R., Rane A., Deloukas P. The largest prospective warfarin-treated cohort supports genetic forecasting. Blood 2009, 113:784-792.
46. Benjamini Y., Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R Statist Soc B 1995, 57:289-300.
47. Gray L.R., Tompkins S.C., Taylor E.B. Regulation of pyruvate metabolism and human disease. Cell. Mol. Life Sci. 2014, 71:2577-2604.
48. Legido A., Jethva R., Goldenthal M.J. Mitochondrial dysfunction in autism. Semin. Pediatr. Neurol. 2013, 20:163-175.
49. Salminen A., Kauppinen A., Hiltunen M., Kaarniranta K. Krebs cycle intermediates regulate DNA and histone methylation: epigenetic impact on the aging process. Ageing Res. Rev. 2014, 16:45-65.
50. Labrie V., Pai S., Petronis A. Epigenetics of major psychosis: progress, problems and perspectives. Trends Genet. 2012, 28:427-435.
51. Kato T., Iwamoto K. Comprehensive DNA methylation and hydroxymethylation analysis in the human brain and its implication in mental disorders. Neuropharmacology 2014, 80:133-139.
52. Caldovic L., Tuchman M. N-acetylglutamate and its changing role through evolution. Biochem. J. 2003, 372:279-290.
53. Shi D., Allewell N.M., Tuchman M. The N-acetylglutamate synthase family: structure, function and mechanisms. Int. J. Mol. Sci. 2015, 16:13004-13022.
54. Bronte V., Zanovello P. Regulation of immune responses by l-arginine metabolism. Nat. Rev. Immunol. 2005, 5:641-654.
55. Morris S.M. Arginine metabolism: boundaries of our knowledge. J. Nutr. 2007, 137(Suppl. 2):1602S-1609S.
56. Fontoura P.C., Pinto V.L., Matsuura C., Resende A.C., de Bem G.F., Ferraz M.R., Cheniaux E., Brunini T.M., Mendes-Ribeiro A.C. Defective nitric oxide-cyclic guanosine monophosphate signaling in patients with bipolar disorder: a potential role for platelet dysfunction. Psychosom. Med. 2012, 74:873-877.
57. Brown N.C., Andrezza A.C., Young L.T. An updated meta-analysis of oxidative stress markers in bipolar disorder. Psychiatry Res. 2014, 218:61-68.
58. Yanik M., Vural H., Tutkun H., Zoroğlu S.S., Savaş H.A., Herken H., Koçyiğit A., Keleş H., Akyol O. The role of the arginine-nitric oxide pathway in the pathogenesis of bipolar affective disorder. Eur. Arch. Psychiatry Clin. Neurosci. 2004, 254:43-47.
59. Hashimoto K., Fukushima T., Shimizu E., Komatsu N., Watanabe H., Shinoda N., Nakazato M., Kumakiri C., Okada S., Hasegawa H., Imai K., Iyo M. Decreased serum levels of d-serine in patients with schizophrenia: evidence in support of the N-methyl-d-aspartate receptor hypofunction hypothesis of schizophrenia. Arch. Gen. Psychiatry 2003, 60:572-576.
60. Yamada K., Ohnishi T., Hashimoto K., Ohba H., Iwayama-Shigeno Y., Toyoshima M., Okuno A., Takao H., Toyota T., Minabe Y., Nakamura K., Shimizu E., Itokawa M., Mori N., Iyo M., Yoshikawa T. Identification of multiple serine racemase (SRR) mRNA isoforms and genetic analyses of SRR and DAO in schizophrenia and d-serine levels. Biol. Psychiatry 2005, 57:1493-1503.
61. Hashimoto K., Malchow B., Falkai P., Schmitt A. Glutamate modulators as potential therapeutic drugs in schizophrenia and affective disorders. Eur. Ach. Psychiatry Clin. Neurosci. 2013, 263:367-377.
62. Hashimoto K. Targeting of NMDA receptors in new treatments for schizophrenia. Expert Opin. Ther. Targets 2014, 18:1049-1063.
63. Hashimoto K., Yoshida T., Ishikawa M., Fujita Y., Niitsu T., Nakazato M., Watanabe H., Sasaki T., Shiina A., Hashimoto T., Kanahara N., Hasegawa T., Enohara M., Kimura A., Iyo M. Increased serum levels of serine enantiomers in patients with depression. Acta Neuropsychiatr. 2016, 10.1017/neu.2015.59.
64. Hashimoto K. Serine enantiomers as diagnostic biomarkers for schizophrenia and bipolar disorder. Eur. Arch. Psychiatry Clin. Neurosci. 2016, 266:83-85.
65. Sahlin K. Muscle energetics during explosive activities and potential effects of nutrition and training. Sports Med. 2014, 44(Suppl. 2):S167-S173.
66. Trexler E.T., Smith-Ryan A.E., Stout J.R., Hoffman J.R., Wilborn C.D., Sale C., Kreider R.B., Jäger R., Earnest C.P., Bannock L., Campbell B., Kalman D., Ziegenfuss T.N., Antonio J. International society of sports nutrition position stand: beta-alanine. J. Int. Soc. Sports Nutr. Jul 15 2015, 12(30). doi: 10.1186/s12970-015-0090-y.
67. Karanti A., Bobeck C., Osterman M., Kardell M., Tidemalm D., Runeson B., Lichtenstein P., Landén M. Gender differences in the treatment of patients with bipolar disorder: a study of 7354 patients. J. Affect. Disord. 2015, 174:303-309.