Psychiatry Research: Neuroimaging
Volume 173, Issue 2 , Pages 143-149 , 30 August 2009

Oral glycine administration increases brain glycine/creatine ratios in men: A proton magnetic resonance spectroscopy study

  • Marc J. Kaufman

      Affiliations

    • Brain Imaging Center, McLean Hospital, Harvard Medical School, Belmont, MA 02478, United States
    • Corresponding Author InformationCorresponding author. Brain Imaging Center, McLean Hospital, 115 Mill Street, Belmont, MA 02478 United States. Tel.: +1 617 855 3469; fax: +1 617 855 2770.
    • ,
  • Andrew P. Prescot

      Affiliations

    • Brain Imaging Center, McLean Hospital, Harvard Medical School, Belmont, MA 02478, United States
    • ,
  • Dost Ongur

      Affiliations

    • Brain Imaging Center, McLean Hospital, Harvard Medical School, Belmont, MA 02478, United States
    • ,
  • A. Eden Evins

      Affiliations

    • Massachusetts General Hospital, Boston, MA 02114, United States
    • ,
  • Tanya L. Barros

      Affiliations

    • Brain Imaging Center, McLean Hospital, Harvard Medical School, Belmont, MA 02478, United States
    • ,
  • Carissa L. Medeiros

      Affiliations

    • Brain Imaging Center, McLean Hospital, Harvard Medical School, Belmont, MA 02478, United States
    • ,
  • Julie Covell

      Affiliations

    • Brain Imaging Center, McLean Hospital, Harvard Medical School, Belmont, MA 02478, United States
    • ,
  • Liqun Wang

      Affiliations

    • Translational Medicine and Genetics, GlaxoSmithKline, Greenford, United Kingdom
    • ,
  • Maurizio Fava

      Affiliations

    • Massachusetts General Hospital, Boston, MA 02114, United States
    • ,
  • Perry F. Renshaw

      Affiliations

    • Brain Imaging Center, McLean Hospital, Harvard Medical School, Belmont, MA 02478, United States
    • The Brain Institute, University of Utah, Salt Lake City, UT, United States

Received 13 April 2008 ,Revised 5 March 2009 ,Accepted 10 March 2009.

References 

  1. Aprison MH, Shank RP, Davidoff RA. A comparison of the concentration of glycine, a transmitter suspect, in different areas of the brain and spinal cord in seven different vertebrates. Comparative Biochemistry and Physiology. 1969;28:1345–1355
  2. Backstrom P, Hyytia P. Ionotropic and metabotropic glutamate receptor antagonism attenuates cue-induced cocaine seeking. Neuropsychopharmacology. 2006;31:778–786
  3. Behar KL, Rothman DL, Spencer DD, Petroff OA. Analysis of macromolecule resonances in 1H NMR spectra of human brain. Magnetic Resonance in Medicine. 1994;32:294–302
  4. Bergeron R, Meyer TM, Coyle JT, Greene RW. Modulation of N-methyl-D-aspartate receptor function by glycine transport. Proceedings of the National Academy of Sciences of the United States of America. 1998;95:15730–15734
  5. Billups D, Attwell D. Active release of glycine or D-serine saturates the glycine site of NMDA receptors at the cerebellar mossy fibre to granule cell synapse. European Journal of Neuroscience. 2003;18:2975–2980
  6. Bisaga A, Popik P. In search of a new pharmacological treatment for drug and alcohol addiction: N-methyl-D-aspartate (NMDA) antagonists. Drug and Alcohol Dependence. 2000;59:1–15
  7. Boulay D, Pichat P, Dargazanli G, Estenne-Bouhtou G, Terranova JP, Rogacki N, et al. Characterization of SSR103800, a selective inhibitor of the glycine transporter-1 in models predictive of therapeutic activity in schizophrenia. Pharmacology, Biochemistry and Behavior. 2008;91:47–58
  8. Buchanan RW, Javitt DC, Marder SR, Schooler NR, Gold JM, McMahon RP, et al. The Cognitive and Negative Symptoms in Schizophrenia Trial (CONSIST): the efficacy of glutamatergic agents for negative symptoms and cognitive impairments. American Journal of Psychiatry. 2007;164:1593–1602
  9. Choi C, Bhardwaj PP, Seres P, Kalra S, Tibbo PG, Coupland NJ. Measurement of glycine in human brain by triple refocusing 1H-MRS in vivo at 3.0T. Magnetic Resonance in Medicine. 2008;59:59–64
  10. Costa J, Khaled E, Sramek J, Bunney W, Potkin SG. An open trial of glycine as an adjunct to neuroleptics in chronic treatment-refractory schizophrenics. Journal of Clinical Psychopharmacology. 1990;10:71–72
  11. Coyle JT. Substance use disorders and schizophrenia: a question of shared glutamatergic mechanisms. Neurotoxicity Research. 2006;10:221–233
  12. Depoortere R, Dargazanli G, Estenne-Bouhtou G, Coste A, Lanneau C, Desvignes C, et al. Neurochemical, electrophysiological and pharmacological profiles of the selective inhibitor of the glycine transporter-1 SSR504734, a potential new type of antipsychotic. Neuropsychopharmacology. 2005;30:1963–1985
  13. Dopico JG, Gonzalez-Hernandez T, Perez IM, Garcia IG, Abril AM, Inchausti JO, et al. Glycine release in the substantia nigra: interaction with glutamate and GABA. Neuropharmacology. 2006;50:548–557
  14. D'Souza DC, Gil R, Cassello K, Morrissey K, Abi-Saab D, White J, et al. IV glycine and oral D-cycloserine effects on plasma and CSF amino acids in healthy humans. Biological Psychiatry. 2000;47:450–462
  15. Evins AE, Fitzgerald SM, Wine L, Rosselli R, Goff DC. Placebo-controlled trial of glycine added to clozapine in schizophrenia. American Journal of Psychiatry. 2000;157:826–828
  16. Flogel U, Niendorf T, Serkowa N, Brand A, Henke J, Leibfritz D. Changes in organic solutes, volume, energy state, and metabolism associated with osmotic stress in a glial cell line: a multinuclear NMR study. Neurochemical Research. 1995;20:793–802
  17. Galli A, Mori F, Bargellini M, Coppini L. Sodium-dependent release of exogenous glycine from preloaded rat hippocampal synaptosomes. Journal of Neural Transmission. General Section. 1993;93:167–179
  18. Goff DC, Tsai G, Manoach DS, Flood J, Darby DG, Coyle JT. D-cycloserine added to clozapine for patients with schizophrenia. American Journal of Psychiatry. 1996;153:1628–1630
  19. Govindaraju V, Young K, Maudsley AA. Proton NMR chemical shifts and coupling constants for brain metabolites. NMR in Biomedicine. 2000;13:129–153
  20. Gozzi A, Herdon H, Schwarz A, Bertani S, Crestan V, Turrini G, et al. Pharmacological stimulation of NMDA receptors via co-agonist site suppresses fMRI response to phencyclidine in the rat. Psychopharmacology (Berlin). 2008;201:273–284
  21. Gundlach AL, Beart PM. Neurochemical studies of the mesolimbic dopaminergic pathway: glycinergic mechanisms and glycinergic-dopaminergic interactions in the rat ventral tegmentum. Journal of Neurochemistry. 1982;38:574–581
  22. Harsing LG, Solyom S, Salamon C. The role of glycineB binding site and glycine transporter (GlyT1) in the regulation of [3H]GABA and [3H]glycine release in the rat brain. Neurochemical Research. 2001;26:915–923
  23. Hashimoto K, Fujita Y, Ishima T, Chaki S, Iyo M. Phencyclidine-induced cognitive deficits in mice are improved by subsequent subchronic administration of the glycine transporter-1 inhibitor NFPS and D-serine. European Neuropsychopharmacology. 2008;18:414–421
  24. Hayashi Y, Ishibashi H, Hashimoto K, Nakanishi H. Potentiation of the NMDA receptor-mediated responses through the activation of the glycine site by microglia secreting soluble factors. Glia. 2006;53:660–668
  25. Hejazi N, Zhou C, Oz M, Sun H, Ye JH, Zhang L. Delta9-tetrahydrocannabinol and endogenous cannabinoid anandamide directly potentiate the function of glycine receptors. Molecular Pharmacology. 2006;69:991–997
  26. Hejnum S, Hassel B. High-affinity glycine and glutamate transport in pig forebrain white and gray matter: a quantitative study. Neurochemistry International. 2007;50:696–702
  27. Heresco-Levy U, Javitt DC, Ermilov M, Mordel C, Horowitz A, Kelly D. Double-blind, placebo-controlled, crossover trial of glycine adjuvant therapy for treatment-resistant schizophrenia. British Journal of Psychiatry. 1996;169:610–617
  28. Heresco-Levy U, Javitt DC, Ermilov M, Mordel C, Silipo G, Lichtenstein M. Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia. Archives of General Psychiatry. 1999;56:29–36
  29. Heresco-Levy U, Ermilov M, Lichtenberg P, Bar G, Javitt DC. High-dose glycine added to olanzapine and risperidone for the treatment of schizophrenia. Biological Psychiatry. 2004;55:165–171
  30. Huang H, Barakat L, Wang D, Bordey A. Bergmann glial GlyT1 mediates glycine uptake and release in mouse cerebellar slices. Journal of Physiology. 2004;560:721–736
  31. Hurd R, Sailasuta N, Srinivasan R, Vigneron DB, Pelletier D, Nelson SJ. Measurement of brain glutamate using TE-averaged PRESS at 3T. Magnetic Resonance in Medicine. 2004;51:435–440
  32. Javitt DC, Zukin SR. Recent advances in the phencyclidine model of schizophrenia. American Journal of Psychiatry. 1991;148:1301–1308
  33. Javitt DC, Zylberman I, Zukin SR, Heresco-Levy U, Lindenmayer JP. Amelioration of negative symptoms in schizophrenia by glycine. American Journal of Psychiatry. 1994;151:1234–1236
  34. Javitt DC, Silipo G, Cienfuegos A, Shelley AM, Bark N, Park M, et al. Adjunctive high-dose glycine in the treatment of schizophrenia. International Journal of Neuropsychopharmacology. 2001;4:385–391
  35. Javitt DC, Duncan L, Balla A, Sershen H. Inhibition of system A-mediated glycine transport in cortical synaptosomes by therapeutic concentrations of clozapine: implications for mechanisms of action. Molecular Psychiatry. 2005;10:276–287
  36. Johnson JW, Ascher P. Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature. 1987;325:529–531
  37. Kanahara N, Shimizu E, Ohgake S, Fujita Y, Kohno M, Hashimoto T, et al. Glycine and D:-serine, but not D:-cycloserine, attenuate prepulse inhibition deficits induced by NMDA receptor antagonist MK-801. Psychopharmacology (Berlin). 2008;198:363–374
  38. Karasawa J, Hashimoto K, Chaki S. D-serine and a glycine transporter inhibitor improve MK-801-induced cognitive deficits in a novel object recognition test in rats. Behavioural Brain Research. 2008;186:78–83
  39. Kaufman MJ, Henry ME, Frederick BdeB, Hennen J, Villafuerte RA, Stoddard EP, et al. Selective serotonin reuptake inhibitor discontinuation syndrome is associated with a rostral anterior cingulate choline metabolite decrease: a proton magnetic resonance spectroscopic imaging study. Biological Psychiatry. 2003;54:534–539
  40. Kessler M, Terramani T, Lynch G, Baudry M. A glycine site associated with N-methyl-D-aspartic acid receptors: characterization and identification of a new class of antagonists. Journal of Neurochemistry. 1989;52:1319–1328
  41. Kleckner NW, Dingledine R. Requirement for glycine in activation of NMDA-receptors expressed in Xenopus oocytes. Science. 1988;241:835–837
  42. Konradsson A, Marcus MM, Hertel P, Svensson TH, Jardemark KE. Inhibition of the glycine transporter GlyT-1 potentiates the effect of risperidone, but not clozapine, on glutamatergic transmission in the rat medial prefrontal cortex. Synapse. 2006;60:102–108
  43. Labrie V, Lipina T, Roder JC. Mice with reduced NMDA receptor glycine affinity model some of the negative and cognitive symptoms of schizophrenia. Psychopharmacology (Berlin). 2008;200:217–230
  44. Lane HY, Chang YC, Liu YC, Chiu CC, Tsai GE. Sarcosine or D-serine add-on treatment for acute exacerbation of schizophrenia: a randomized, double-blind, placebo-controlled study. Archives of General Psychiatry. 2005;62:1196–1204
  45. Leiderman E, Zylberman I, Zukin SR, Cooper TB, Javitt DC. Preliminary investigation of high-dose oral glycine on serum levels and negative symptoms in schizophrenia: an open-label trial. Biological Psychiatry. 1996;39:213–215
  46. Linn GS, O'Keeffe RT, Lifshitz K, Schroeder C, Javitt DC. Behavioral effects of orally administered glycine in socially housed monkeys chronically treated with phencyclidine. Psychopharmacology (Berlin). 2007;192:27–38
  47. Martin G, Guadano-Ferraz A, Morte B, Ahmed S, Koob GF, De Lecea L, et al. Chronic morphine treatment alters N-methyl-D-aspartate receptors in freshly isolated neurons from nucleus accumbens. Journal of Pharmacology and Experimental Therapeutics. 2004;311:265–273
  48. Neumeister A, Carson R, Henry S, Planeta-Wilson B, Binneman B, Maguire RP, et al. Cerebral metabolic effects of intravenous glycine in healthy human subjects. Journal of Clinical Psychopharmacology. 2006;26:595–599
  49. Ogg RJ, Kingsley PB, Taylor JS. WET, a T1- and B1-insensitive water-suppression method for in vivo localized 1H NMR spectroscopy. Journal of Magnetic Resonance B. 1994;104:1–10
  50. Olney JW, Farber NB. Glutamate receptor dysfunction and schizophrenia. Archives of General Psychiatry. 1995;52:998–1007
  51. Potkin SG, Jin Y, Bunney BG, Costa J, Gulasekaram B. Effect of clozapine and adjunctive high-dose glycine in treatment-resistant schizophrenia. American Journal of Psychiatry. 1999;156:145–147
  52. Prescot AP, Frederick BdeB, Wang L, Brown J, Jensen JE, Kaufman MJ, et al. In vivo detection of brain glycine with echo-time-averaged (1)H magnetic resonance spectroscopy at 4.0 T. Magnetic Resonance in Medicine. 2006;55:681–686
  53. Provencher SW. Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magnetic Resonance in Medicine. 1993;30:672–679
  54. Provencher SW. In: LCModel and LCMgui User's Manual. 2005;p. 163
  55. Roberto M, Schweitzer P, Madamba SG, Stouffer DG, Parsons LH, Siggins GR. Acute and chronic ethanol alter glutamatergic transmission in rat central amygdala: an in vitro and in vivo analysis. Journal of Neuroscience. 2004;24:1594–1603
  56. Rosse RB, Theut SK, Banay-Schwartz M, Leighton M, Scarcella E, Cohen CG, et al. Glycine adjuvant therapy to conventional neuroleptic treatment in schizophrenia: an open-label, pilot study. Clinical Neuropharmacology. 1989;12:416–424
  57. Roux MJ, Supplisson S. Neuronal and glial glycine transporters have different stoichiometries. Neuron. 2000;25:373–383
  58. Silk DB, Kumar PJ, Perrett D, Clark ML, Dawson AM. Amino acid and peptide absorption in patients with coeliac disease and dermatitis herpetiformis. Gut. 1974;15:1–8
  59. Stoll B, Henry J, Reeds PJ, Yu H, Jahoor F, Burrin DG. Catabolism dominates the first-pass intestinal metabolism of dietary essential amino acids in milk protein-fed piglets. Journal of Nutrition. 1998;128:606–614
  60. Toth E, Lajtha A. Elevation of cerebral levels of nonessential amino acids in vivo by administration of large doses. Neurochemical Research. 1981;6:1309–1317
  61. Toth E, Lajtha A. Antagonism of phencyclidine-induced hyperactivity by glycine in mice. Neurochemical Research. 1986;11:393–400
  62. Tsai GE, Yang P, Chung LC, Tsai IC, Tsai CW, Coyle JT. D-serine added to clozapine for the treatment of schizophrenia. American Journal of Psychiatry. 1999;156:1822–1825
  63. Urenjak J, Williams SR, Gadian DG, Noble M. Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types. Journal of Neuroscience. 1993;13:981–989
  64. Vengeliene V, Bachteler D, Danysz W, Spanagel R. The role of the NMDA receptor in alcohol relapse: a pharmacological mapping study using the alcohol deprivation effect. Neuropharmacology. 2005;48:822–829
  65. Viola A, Chabrol B, Nicoli F, Confort-Gouny S, Viout P, Cozzone PJ. Magnetic resonance spectroscopy study of glycine pathways in nonketotic hyperglycinemia. Pediatric Research. 2002;52:292–300
  66. Waziri R. Glycine therapy of schizophrenia. Biological Psychiatry. 1988;23:210–211
  67. Williams JB, Mallorga PJ, Conn PJ, Pettibone DJ, Sur C. Effects of typical and atypical antipsychotics on human glycine transporters. Schizophrenia Research. 2004;71:103–112
  68. Wojcik SM, Katsurabayashi S, Guillemin I, Friauf E, Rosenmund C, Brose N, et al. A shared vesicular carrier allows synaptic corelease of GABA and glycine. Neuron. 2006;50:575–587
  69. Wu G. Intestinal mucosal amino acid catabolism. Journal of Nutrition. 1998;128:1249–1252
  70. Zafra F, Aragon C, Olivares L, Danbolt NC, Gimenez C, Storm-Mathisen J. Glycine transporters are differentially expressed among CNS cells. Journal of Neuroscience. 1995;15:3952–3969

PII: S0925-4927(09)00066-3

doi: 10.1016/j.pscychresns.2009.03.004

Psychiatry Research: Neuroimaging
Volume 173, Issue 2 , Pages 143-149 , 30 August 2009

Article Tools

* Image Usage & Resolution