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Effect of l-theanine on glutamatergic function in patients with schizophrenia

  • Miho Ota (a1), Chisato Wakabayashi (a1), Noriko Sato (a2), Hiroaki Hori (a1), Kotaro Hattori (a1), Toshiya Teraishi (a1), Hayato Ozawa (a3), Tsutomu Okubo (a3) and Hiroshi Kunugi (a1)...
Abstract
Objectives

Glutamatergic dysfunction in the brain has been implicated in the pathophysiology of schizophrenia. Previous studies suggested that l-theanine affects the glutamatergic neurotransmission and ameliorates symptoms in patients with schizophrenia. The aims of the present study were twofold: to examine the possible effects of l-theanine on symptoms in chronic schizophrenia patients and to evaluate the changes in chemical mediators, including glutamate + glutamine (Glx), in the brain by using 1H magnetic resonance spectroscopy (MRS).

Method

The subjects were 17 patients with schizophrenia and 22 age- and sex-matched healthy subjects. l-Theanine (250 mg/day) was added to the patients’ ongoing antipsychotic treatment for 8 weeks. The outcome measures were the Positive and Negative Syndrome Scale (PANSS), Pittsburgh Sleep Quality Index scores and MRS results.

Results

There were significant improvements in the PANSS positive scale and sleep quality after the l-theanine treatment. As for MRS, we found no significant differences in Glx levels before and after the 8 week l-theanine treatment. However, significant correlations were observed between baseline density of Glx and change in Glx density by l-theanine.

Conclusions

Our results suggest that l-theanine is effective in ameliorating positive symptoms and sleep quality in schizophrenia. The MRS findings suggest that l-theanine stabilises the glutamatergic concentration in the brain, which is a possible mechanism underlying the therapeutic effect.

Copyright
Corresponding author
Dr. Miho Ota, Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry 4-1-1, Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan. Tel: +81 42 341 2712; Fax: +81 42 346 2094; E-mail: ota@ncnp.go.jp
References
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1. Tsai, G, Van Kammen, DP, Chen, S, Kelley, ME, Grier, A, Coyle, JT. Glutamatergic neurotransmission involves structural and clinical deficits of schizophrenia. Biol Psychiatry 1998;44:667674.
2. Bartha, R, Williamson, PC, Drost, DJ et al. Measurement of glutamate and glutamine in the medial prefrontal cortex of never-treated schizophrenic patients and healthy controls using proton magnetic resonance spectroscopy. Arch Gen Psychiatry 1997;54:959965.
3. Théberge, J, Bartha, R, Drost, DJ et al. Glutamate and glutamine measured with 4.0 T proton MRS in never-treated patients with schizophrenia and healthy volunteers. Am J Psychiatry 2002;159:19441946.
4. Kegeles, LS, Mao, X, Stanford, AD et al. Elevated prefrontal cortex γ-aminobutyric acid and glutamate-glutamine levels in schizophrenia measured in vivo with proton magnetic resonance spectroscopy. Arch Gen Psychiatry 2012;69:449459.
5. Marsman, A, Van Den Heuvel, MP, Klomp, DW, Kahn, RS, Luijten, PR, Hulshoff Pol, HE. Glutamate in schizophrenia: a focused review and meta-analysis of 1 h-MRS studies. Schizophr Bull 2013;39:120129.
6. Théberge, J, Al-Semaan, Y, Williamson, PC et al. Glutamate and glutamine in the anterior cingulate and thalamus of medicated patients with chronic schizophrenia and healthy comparison subjects measured with 4.0-T proton MRS. Am J Psychiatry 2003;160:22312233.
7. Natsubori, T, Inoue, H, Abe, O et al. Reduced frontal glutamate + glutamine and n-acetylaspartate levels in patients with chronic schizophrenia but not in those at clinical high risk for psychosis or with first-episode schizophrenia. Schizophr Bull 2014;40:11281139.
8. Ota, M, Ishikawa, M, Sato, N et al. Glutamatergic changes in the cerebral white matter associated with schizophrenic exacerbation. Acta Psychiatr Scand 2012;126:7278.
9. De Mejia, EG, Ramirez-Mares, MV, Puangpraphant, S. Bioactive components of tea: cancer, inflammation and behavior. Brain Behav Immun 2009;23:721731.
10. Nathan, PJ, Lu, K, Gray, M, Oliver, C. The neuropharmacology of l-theanine (N-ethyl-l-glutamine): a possible neuroprotective and cognitive enhancing agent. J Herb Pharmacother 2006;6:2130.
11. Kakuda, T, Nozawa, A, Sugimoto, A, Niino, H. Inhibition by theanine of binding of [3H]AMPA, [3H]kainate, and [3H]MDL 105,519 to glutamate receptors. Biosci Biotechnol Biochem 2002;66:26832686.
12. Kakuda, T, Hinoi, E, Abe, A, Nozawa, A, Ogura, M, Yoneda, Y. Theanine, an ingredient of green tea, inhibits [3H]glutamine transport in neurons and astroglia in rat brain. J Neurosci Res 2008;86:18461856.
13. Wakabayashi, C, Numakawa, T, Ninomiya, M et al. Behavioral and molecular evidence for psychotropic effects in l-theanine. Psychopharmacology (Berl) 2012;219:10991109.
14. Ota, M, Wakabayashi, C, Matsuo, J et al. Effect of l-theanine on sensorimotor gating in human subjects. Psychiatry Clin Neurosci 2013;68:337343.
15. Lu, K, Gray, MA, Oliver, C et al. The acute effects of l-theanine in comparison with alprazolam on anticipatory anxiety in humans. Hum Psychopharmacol 2004;19:457465.
16. Ritsner, MS, Miodownik, C, Ratner, Y et al. l-Theanine relieves positive, activation, and anxiety symptoms in patients with schizophrenia and schizoaffective disorder: an 8-week, randomized, double-blind, placebo-controlled, 2-center study. J Clin Psychiatry 2011;72:3442.
17. Miodownik, C, Maayan, R, Ratner, Y et al. Serum levels of brain-derived neurotrophic factor and cortisol to sulfate of dehydroepiandrosterone molar ratio associated with clinical response to l-theanine as augmentation of antipsychotic therapy in schizophrenia and schizoaffective disorder patients. Clin Neuropharmacol 2011;34:155160.
18. Unno, K, Tanida, N, Ishii, N et al. Anti-stress effect of theanine on students during pharmacy practice: positive correlation among salivary α-amylase activity, trait anxiety and subjective stress. Pharmacol Biochem Behav 2013;111:128135.
19. Lyon, MR, Kapoor, MP, Juneja, LR. The effects of l-theanine (Suntheanine®) on objective sleep quality in boys with attention deficit hyperactivity disorder (ADHD): a randomized, double-blind, placebo-controlled clinical trial. Altern Med Rev 2011;16:348354.
20. Ozeki, M, Juneja, LR, Shirakawa, S. The effects of theanine on sleep with the actigraph as physiological indicator. Jpn J Physiol Anthropol 2004;9:143150.
21. American Psychiatric Association. DSM-IV: diagnostic and statistical manual of mental disorders, 4th edn. Washington, DC: American Psychiatric Press Inc, 1994.
22. Kay, SR, Opler, LA, Fiszbein, A. Positive and Negative Syndrome Scale (PANSS) manual. Schizophr Bull 1987;13:261276.
23. Otsubo, T, Tanaka, K, Koda, R et al. Reliability and validity of Japanese version of the mini-international neuropsychiatric interview. Psychiatry Clin Neurosci 2005;59:517526.
24. Sheehan, DV, Lecrubier, Y, Sheehan, KH et al. 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;59:2257.
25. Buysse, DJ, Reynolds, CF 3rd, Monk, TH, Berman, SR, Kupfer, DJ. The Pittsburgh sleep quality index: a new instrument for psychiatric practice and research. Psychiatry Res 1989;28:193213.
26. Provencher, SW. Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med 1993;30:672679.
27. Rowland, LM, Spieker, EA, Francis, A, Barker, PB, Carpenter, WT, Buchanan, RW. White matter alterations in deficit schizophrenia. Neuropsychopharmacology 2009;34:15141522.
28. Barker, PB, Soher, BJ, Blackband, SJ, Chatham, JC, Mathews, VP, Bryan, RN. Quantitation of proton NMR spectra of the human brain using tissue water as an internal concentration standard. NMR Biomed 1993;6:8994.
29. American Psychiatric Association. Practice guidelines for the treatment of patients with schizophrenia. Washington, DC: American Psychiatric Press Inc., 1997.
30. Inagaki, A, Inada, T. Dose equivalence of psychotropic drugs. partxviii: dose equivalence of psychotropic drugs: 2006-version. Jpn J Clin Psychopharmacol 2006;9:14431447.
31. Yokogoshi, H, Terashima, T. Effect of theanine, r-lutamylethylamide, on brain monoamines, striatal dopamine release and some kinds of behaviour in rats. Nutrition 2000;16:776777.
32. Braff, DL, Geyer, MA. Sensorimotor gating and schizophrenia. Human and animal model studies. Arch Gen Psychiatry 1990;47:181188.
33. Kunugi, H, Tanaka, M, Hori, H, Hashimoto, R, Saitoh, O, Hironaka, N. Prepulse inhibition of acoustic startle in japanese patients with chronic schizophrenia. Neurosci Res 2007;59:2328.
34. Ito, H, Takano, H, Arakawa, R et al. Effects of dopamine D2 receptor partial agonist antipsychotic aripiprazole on dopamine synthesis in human brain measured by PET with l-[β-11C]DOPA. PLoS One 2012;7:e46488.
35. Théberge, J, Williamson, KE, Aoyama, N et al. Longitudinal grey-matter and glutamatergic losses in first-episode schizophrenia. Br J Psychiatry 2007;191:325354.
36. Van Elst, LT, Valerius, G, Büchert, M et al. Increased prefrontal and hippocampal glutamate concentration in schizophrenia: evidence from a magnetic resonance spectroscopy study. Biol Psychiatry 2005;58:724730.
37. Pakkenberg, B, Scheel-Kruger, J, Kristiansen, LV. Schizophrenia; from structure to function with special focus on the mediodorsal thalamic prefrontal loop. Acta Psychiatr Scand 2009;120:345354.
38. Tibbo, P, Hanstock, C, Valiakalayil, A, Allen, P. 3-T proton MRS investigation of glutamate and glutamine in adolescents at high genetic risk for schizophrenia. Am J Psychiatry 2004;161:11161118.
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Acta Neuropsychiatrica
  • ISSN: 0924-2708
  • EISSN: 1601-5215
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