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Current Neuropharmacology

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ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

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General Research Article

A Preliminary Nuclear Magnetic Resonance Metabolomics Study Identifies Metabolites that Could Serve as Diagnostic Markers of Major Depressive Disorder

Author(s): Ibrahim Mohammed Badamasi, Maulidiani Maulidiani, Munn Sann Lye, Normala Ibrahim, Khozirah Shaari and Johnson Stanslas*

Volume 20, Issue 5, 2022

Published on: 14 March, 2022

Page: [965 - 982] Pages: 18

DOI: 10.2174/1570159X19666210611095320

Price: $65

Abstract

Background: The evaluation of metabolites that are directly involved in the physiological process, few steps short of phenotypical manifestation, remains vital for unravelling the biological moieties involved in the development of the (MDD) and in predicting its treatment outcome.

Methodology: Eight (8) urine and serum samples each obtained from consenting healthy controls (HC), twenty-five (25) urine and serum samples each from first episode treatment naïve MDD (TNMDD) patients, and twenty (22) urine and serum samples each s from treatment naïve MDD patients 2 weeks after SSRI treatment (TWMDD) were analysed for metabolites using proton nuclear magnetic resonance (1HNMR) spectroscopy. The evaluation of patients’ samples was carried out using Partial Least Squares Discriminant Analysis (PLS-DA) and Orthogonal Partial Least Square- Discriminant Analysis (OPLSDA) models.

Results: In the serum, decreased levels of lactate, glucose, glutamine, creatinine, acetate, valine, alanine, and fatty acid and an increased level of acetone and choline in TNMDD or TWMDD irrespective of whether an OPLSDA or PLSDA evaluation was used were identified. A test for statistical validations of these models was successful.

Conclusion: Only some changes in serum metabolite levels between HC and TNMDD identified in this study have potential values in the diagnosis of MDD. These changes included decreased levels of lactate, glutamine, creatinine, valine, alanine, and fatty acid, as well as an increased level of acetone and choline in TNMDD. The diagnostic value of these changes in metabolites was maintained in samples from TWMDD patients, thus reaffirming the diagnostic nature of these metabolites for MDD.

Keywords: 1H NMR, metabolomics, urine, serum diagnosis, prognosis, MDD.

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[1]
Ellero-Simatos, S.; Lewis, J.P.; Georgiades, A.; Yerges-Armstrong, L.M.; Beitelshees, A.L.; Horenstein, R.B.; Dane, A.; Harms, A.C.; Ramaker, R.; Vreeken, R.J.; Perry, C.G.; Zhu, H.; Sànchez, C.L.; Kuhn, C.; Ortel, T.L.; Shuldiner, A.R.; Hankemeier, T.; Kaddurah-Daouk, R. Pharmacometabolomics reveals that serotonin is implicated in aspirin response variability. CPT Pharmacometrics Syst. Pharmacol., 2014, 3, e125.
[http://dx.doi.org/10.1038/psp.2014.22] [PMID: 25029353]
[2]
Nicholson, J.K.; Wilson, I.D.; Lindon, J.C. Pharmacometabonomics as an effector for personalized medicine. Pharmacogenomics, 2011, 12(1), 103-111.
[http://dx.doi.org/10.2217/pgs.10.157] [PMID: 21174625]
[3]
Carabotti, M.; Scirocco, A.; Maselli, M.A.; Severi, C. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann. Gastroenterol., 2015, 28(2), 203-209.
[PMID: 25830558]
[4]
Foster, J.A.; McVey Neufeld, K.A. Gut-brain axis: how the microbiome influences anxiety and depression. Trends Neurosci., 2013, 36(5), 305-312.
[http://dx.doi.org/10.1016/j.tins.2013.01.005] [PMID: 23384445]
[5]
Tian, J.S.; Shi, B.Y.; Xiang, H.; Gao, S.; Qin, X.M.; Du, G.H. 1H-NMR-based metabonomic studies on the anti-depressant effect of genipin in the chronic unpredictable mild stress rat model. PLoS One, 2013, 8(9), e75721.
[http://dx.doi.org/10.1371/journal.pone.0075721] [PMID: 24058700]
[6]
Bjerrum, J.T.; Nielsen, O.H.; Hao, F.; Tang, H.; Nicholson, J.K.; Wang, Y.; Olsen, J. Metabonomics in ulcerative colitis: diagnostics, biomarker identification, and insight into the pathophysiology. J. Proteome Res., 2010, 9(2), 954-962.
[http://dx.doi.org/10.1021/pr9008223] [PMID: 19860486]
[7]
Bertram, H.C.; Duus, J.Ø.; Petersen, B.O.; Hoppe, C.; Larnkjaer, A.; Schack-Nielsen, L.; Mølgaard, C.; Michaelsen, K.F. Nuclear magnetic resonance-based metabonomics reveals strong sex effect on plasma metabolism in 17-year-old Scandinavians and correlation to retrospective infant plasma parameters. Metabolism, 2009, 58(7), 1039-1045.
[http://dx.doi.org/10.1016/j.metabol.2009.03.011] [PMID: 19411084]
[8]
Serrano-Contreras, J.I.; García-Pérez, I.; Meléndez-Camargo, M.E.; Zepeda-Vallejo, L.G. NMR-based metabonomic analysis of normal rat urine and faeces in response to (±)-venlafaxine treatment. J. Pharm. Biomed. Anal., 2016, 123, 82-92.
[http://dx.doi.org/10.1016/j.jpba.2016.01.044] [PMID: 26895493]
[9]
Brown, P.N.; Murch, S.J.; Shipley, P. Phytochemical diversity of cranberry (Vaccinium macrocarpon Aiton) cultivars by anthocyanin determination and metabolomic profiling with chemometric analysis. J. Agric. Food Chem., 2012, 60(1), 261-271.
[http://dx.doi.org/10.1021/jf2033335] [PMID: 22148867]
[10]
Uher, R.; Payne, J.L.; Pavlova, B.; Perlis, R.H. Major depressive disorder in DSM-5: implications for clinical practice and research of changes from DSM-IV. Depress. Anxiety, 2014, 31(6), 459-471.
[http://dx.doi.org/10.1002/da.22217] [PMID: 24272961]
[11]
Bauer, M.; Bschor, T.; Pfennig, A.; Whybrow, P.C.; Angst, J.; Versiani, M.; Möller, H.J. World federation of societies of biological psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders in primary care. World J. Biol. Psychiatry, 2007, 8(2), 67-104.
[http://dx.doi.org/10.1080/15622970701227829] [PMID: 17455102]
[12]
Beckonert, O.; Keun, H.C.; Ebbels, T.M.D.; Bundy, J.; Holmes, E.; Lindon, J.C.; Nicholson, J.K. Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts. Nat. Protoc., 2007, 2(11), 2692-2703.
[http://dx.doi.org/10.1038/nprot.2007.376] [PMID: 18007604]
[13]
Mahadevan, S.; Shah, S.L.; Marrie, T.J.; Slupsky, C.M. Analysis of metabolomic data using support vector machines. Anal. Chem., 2008, 80(19), 7562-7570.
[http://dx.doi.org/10.1021/ac800954c] [PMID: 18767870]
[14]
Cloarec, O.; Dumas, M.E.; Trygg, J.; Craig, A.; Barton, R.H.; Lindon, J.C.; Nicholson, J.K.; Holmes, E. Evaluation of the orthogonal projection on latent structure model limitations caused by chemical shift variability and improved visualization of biomarker changes in 1H NMR spectroscopic metabonomic studies. Anal. Chem., 2005, 77(2), 517-526.
[http://dx.doi.org/10.1021/ac048803i] [PMID: 15649048]
[15]
Jung, Y.; Lee, J.; Kwon, J.; Lee, K.S.; Ryu, D.H.; Hwang, G.S. Discrimination of the geographical origin of beef by (1)H NMR-based metabolomics. J. Agric. Food Chem., 2010, 58(19), 10458-10466.
[http://dx.doi.org/10.1021/jf102194t] [PMID: 20831251]
[16]
Chen, J.J.; Zhou, C.J.; Zheng, P.; Cheng, K.; Wang, H.Y.; Li, J.; Zeng, L.; Xie, P. Differential urinary metabolites related with the severity of major depressive disorder. Behav. Brain Res., 2017, 332, 280-287.
[http://dx.doi.org/10.1016/j.bbr.2017.06.012] [PMID: 28624318]
[17]
Altamura, C.; Maes, M.; Dai, J.; Meltzer, H.Y. Plasma concentrations of excitatory amino acids, serine, glycine, taurine and histidine in major depression. Eur. Neuropsychopharmacol., 1995, 5(Suppl.), 71-75.
[http://dx.doi.org/10.1016/0924-977X(95)00033-L] [PMID: 8775762]
[18]
Hashimoto, K. Emerging role of glutamate in the pathophysiology of major depressive disorder. Brain Res. Brain Res. Rev., 2009, 61(2), 105-123.
[http://dx.doi.org/10.1016/j.brainresrev.2009.05.005] [PMID: 19481572]
[19]
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(1), 133-140.
[http://dx.doi.org/10.1016/j.euroneuro.2014.11.001] [PMID: 25482684]
[20]
Hashimoto, K.; Sawa, A.; Iyo, M. Increased levels of glutamate in brains from patients with mood disorders. Biol. Psychiatry, 2007, 62(11), 1310-1316.
[http://dx.doi.org/10.1016/j.biopsych.2007.03.017] [PMID: 17574216]
[21]
Mitani, H.; Shirayama, Y.; Yamada, T.; Maeda, K.; Ashby, C.R., Jr; Kawahara, R. Correlation between plasma levels of glutamate, alanine and serine with severity of depression. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2006, 30(6), 1155-1158.
[http://dx.doi.org/10.1016/j.pnpbp.2006.03.036] [PMID: 16707201]
[22]
Mauri, M.C.; Ferrara, A.; Boscati, L.; Bravin, S.; Zamberlan, F.; Alecci, M.; Invernizzi, G. Plasma and platelet amino acid concentrations in patients affected by major depression and under fluvoxamine treatment. Neuropsychobiology, 1998, 37(3), 124-129.
[http://dx.doi.org/10.1159/000026491] [PMID: 9597668]
[23]
Sumiyoshi, T.; Anil, A.E.; Jin, D.; Jayathilake, K.; Lee, M.; Meltzer, H.Y. Plasma glycine and serine levels in schizophrenia compared to normal controls and major depression: relation to negative symptoms. Int. J. Neuropsychopharmacol., 2004, 7(1), 1-8.
[http://dx.doi.org/10.1017/S1461145703003900] [PMID: 14720317]
[24]
Woo, H.I.; Chun, M.R.; Yang, J.S.; Lim, S.W.; Kim, M.J.; Kim, S.W.; Myung, W.J.; Kim, D.K.; Lee, S.Y. Plasma amino acid profiling in major depressive disorder treated with selective serotonin reuptake inhibitors. CNS Neurosci. Ther., 2015, 21(5), 417-424.
[http://dx.doi.org/10.1111/cns.12372] [PMID: 25611566]
[25]
Brunoni, A.R.; Lopes, M.; Fregni, F. A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression. Int. J. Neuropsychopharmacol., 2008, 11(8), 1169-1180.
[http://dx.doi.org/10.1017/S1461145708009309] [PMID: 18752720]
[26]
Duman, R.S.; Monteggia, L.M. A neurotrophic model for stress-related mood disorders. Biol. Psychiatry, 2006, 59(12), 1116-1127.
[http://dx.doi.org/10.1016/j.biopsych.2006.02.013] [PMID: 16631126]
[27]
Paige, L.A.; Mitchell, M.W.; Krishnan, K.R.R.; Kaddurah-Daouk, R.; Steffens, D.C. A preliminary metabolomic analysis of older adults with and without depression. Int. J. Geriatr. Psychiatry, 2007, 22(5), 418-423.
[http://dx.doi.org/10.1002/gps.1690] [PMID: 17048218]
[28]
Sartorius, A.; Hellweg, R.; Litzke, J.; Vogt, M.; Dormann, C.; Vollmayr, B.; Danker-Hopfe, H.; Gass, P. Correlations and discrepancies between serum and brain tissue levels of neurotrophins after electroconvulsive treatment in rats. Pharmacopsychiatry, 2009, 42(6), 270-276.
[http://dx.doi.org/10.1055/s-0029-1224162] [PMID: 19924587]
[29]
Sen, S.; Duman, R.; Sanacora, G. Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications. Biol. Psychiatry, 2008, 64(6), 527-532.
[http://dx.doi.org/10.1016/j.biopsych.2008.05.005] [PMID: 18571629]
[30]
Zhu, H.; Bogdanov, M.B.; Boyle, S.H.; Matson, W.; Sharma, S.; Matson, S.; Churchill, E.; Fiehn, O.; Rush, J.A.; Krishnan, R.R.; Pickering, E.; Delnomdedieu, M.; Kaddurah-Daouk, R. Pharmacometabolomics of response to sertraline and to placebo in major depressive disorder - possible role for methoxyindole pathway. PLoS One, 2013, 8(7), e68283.
[http://dx.doi.org/10.1371/journal.pone.0068283] [PMID: 23874572]
[31]
Kaddurah-Daouk, R.; Bogdanov, M.B.; Wikoff, W.R.; Zhu, H.; Boyle, S.H.; Churchill, E.; Wang, Z.; Rush, A.J.; Krishnan, R.R.; Pickering, E.; Delnomdedieu, M.; Fiehn, O. Pharmacometabolomic mapping of early biochemical changes induced by sertraline and placebo. Transl. Psychiatry, 2013, 3, e223.
[http://dx.doi.org/10.1038/tp.2012.142] [PMID: 23340506]
[32]
Liu, R-P.; Zou, M.; Wang, J-Y.; Zhu, J-J.; Lai, J-M.; Zhou, L-L.; Chen, S-F.; Zhang, X.; Zhu, J-H. Paroxetine ameliorates lipopolysaccharide-induced microglia activation via differential regulation of MAPK signaling. J. Neuroinflammation, 2014, 11(1), 47.
[http://dx.doi.org/10.1186/1742-2094-11-47] [PMID: 24618100]
[33]
Wichers, M.C.; Koek, G.H.; Robaeys, G.; Verkerk, R.; Scharpé, S.; Maes, M. IDO and interferon-α-induced depressive symptoms: a shift in hypothesis from tryptophan depletion to neurotoxicity. Mol. Psychiatry, 2005, 10(6), 538-544.
[http://dx.doi.org/10.1038/sj.mp.4001600] [PMID: 15494706]
[34]
Capuron, L.; Neurauter, G.; Musselman, D.L.; Lawson, D.H.; Nemeroff, C.B.; Fuchs, D.; Miller, A.H. Interferon-alpha-induced changes in tryptophan metabolism. relationship to depression and paroxetine treatment. Biol. Psychiatry, 2003, 54(9), 906-914.
[http://dx.doi.org/10.1016/S0006-3223(03)00173-2] [PMID: 14573318]
[35]
Valkanova, V.; Ebmeier, K.P.; Allan, C.L. CRP, IL-6 and depression: a systematic review and meta-analysis of longitudinal studies. J. Affect. Disord., 2013, 150(3), 736-744.
[http://dx.doi.org/10.1016/j.jad.2013.06.004] [PMID: 23870425]
[36]
Hannestad, J.; DellaGioia, N.; Bloch, M. The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis. Neuropsychopharmacology, 2011, 36(12), 2452-2459.
[http://dx.doi.org/10.1038/npp.2011.132] [PMID: 21796103]
[37]
Nandwani, S.; Saluja, M.; Vats, M.; Mehta, Y. Lactic acidosis In Critically Ill Patients. People’s J. Sci. Res, 2010, 3(1), 43-47.
[38]
Schurr, A. Lactate, not pyruvate, is the end product of glucose metabolism via glycolysis. Carbohydrate, 2017, Available from:, https://www.intechopen.com/books/carbohydrate/lactate-not-pyruvate-is-the-end-product-of-glucose-metabolism-via-glycolysis
[39]
Moat, A.G.; Foster, J.W.; Spector, M.P. Fermentation pathways. In: Microbial Physiology; Moat, A.G.; Foster, J.W.; Spector, M.P., Eds.; Wiley-Liss, Inc, 2002; pp. 412-433.
[http://dx.doi.org/10.1002/0471223867.ch11]
[40]
Gardner, A.; Boles, R.G. Beyond the serotonin hypothesis: mitochondria, inflammation and neurodegeneration in major depression and affective spectrum disorders. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2011, 35(3), 730-743.
[http://dx.doi.org/10.1016/j.pnpbp.2010.07.030] [PMID: 20691744]
[41]
Lopresti, A.L.; Hood, S.D.; Drummond, P.D. A review of lifestyle factors that contribute to important pathways associated with major depression: diet, sleep and exercise. J. Affect. Disord., 2013, 148(1), 12-27.
[http://dx.doi.org/10.1016/j.jad.2013.01.014] [PMID: 23415826]
[42]
Modica-Napolitano, J.S.; Renshaw, P.F. Ethanolamine and phosphoethanolamine inhibit mitochondrial function in vitro: implications for mitochondrial dysfunction hypothesis in depression and bipolar disorder. Biol. Psychiatry, 2004, 55(3), 273-277.
[http://dx.doi.org/10.1016/S0006-3223(03)00784-4] [PMID: 14744468]
[43]
Zubenko, G.S.; Hughes, H.B., III; Jordan, R.M.; Lyons-Weiler, J.; Cohen, B.M. Differential hippocampal gene expression and pathway analysis in an etiology-based mouse model of major depressive disorder. Am. J. Med. Genet. B. Neuropsychiatr. Genet., 2014, 165B(6), 457-466.
[http://dx.doi.org/10.1002/ajmg.b.32257] [PMID: 25059218]

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