Hostname: page-component-78c5997874-8bhkd Total loading time: 0 Render date: 2024-11-15T13:21:05.933Z Has data issue: false hasContentIssue false
  • English
  • Français

Increased serum levels of serine enantiomers in patients with depression

Published online by Cambridge University Press:  29 October 2015

Kenji Hashimoto ,
Taisuke Yoshida ,
Masatomo Ishikawa ,
Yuko Fujita ,
Tomihisa Niitsu ,
Michiko Nakazato ,
Hiroyuki Watanabe ,
Tsuyoshi Sasaki ,
Akihiro Shiina  and
Tasuku Hashimoto
...Show all authors
Kenji Hashimoto*
Affiliation:
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan
Taisuke Yoshida
Affiliation:
Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan
Masatomo Ishikawa
Affiliation:
Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan
Yuko Fujita
Affiliation:
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan
Tomihisa Niitsu
Affiliation:
Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan
Michiko Nakazato
Affiliation:
Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan Research Center for Child Mental Development, Chiba University Center for Forensic Mental Health, Chiba, Japan Department of Child Psychiatry, Chiba University Hospital, Chiba, Japan
Hiroyuki Watanabe
Affiliation:
Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan Division of Medical Treatment and Rehabilitation, Chiba University Center for Forensic Mental Health, Chiba, Japan
Tsuyoshi Sasaki
Affiliation:
Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan Department of Child Psychiatry, Chiba University Hospital, Chiba, Japan
Akihiro Shiina
Affiliation:
Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan Department of Child Psychiatry, Chiba University Hospital, Chiba, Japan
Tasuku Hashimoto
Affiliation:
Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan
Nobuhisa Kanahara
Affiliation:
Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan Division of Medical Treatment and Rehabilitation, Chiba University Center for Forensic Mental Health, Chiba, Japan
Tadashi Hasegawa
Affiliation:
Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan
Masayo Enohara
Affiliation:
Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan
Atsushi Kimura
Affiliation:
Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan
Masaomi Iyo
Affiliation:
Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan Division of Medical Treatment and Rehabilitation, Chiba University Center for Forensic Mental Health, Chiba, Japan Department of Child Psychiatry, Chiba University Hospital, Chiba, Japan
*
Dr. Kenji Hashimoto, Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chiba 260-8670, Japan. Tel: +81-43-226-2517; Fax: +81-43-226-2561; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective

Glutamatergic neurotransmission via the N-methyl-d-aspartate (NMDA) receptor is integral to the pathophysiology of depression. This study was performed to examine whether amino acids related to NMDA receptor neurotransmission are altered in the serum of patients with depression.

Method

We measured the serum levels of d-serine, l-serine, glycine, glutamate and glutamine in patients with depression (n=70), and age-matched healthy subjects (n=78).

Results

Serum levels of d-serine and l-serine in patients with depression were significantly higher than those of healthy controls (p<0.001). In contrast, serum levels of glycine, glutamate and glutamine did not differ between the two groups. Interestingly, the ratio of l-serine to glycine in patients was significantly higher than that of healthy controls (p<0.001).

Conclusion

This study suggests that serine enantiomers may be peripheral biomarkers for depression, and that abnormality in the d-serine-l-serine-glycine cycle plays a role in the pathophysiology of depression.

Keywords

biomarkerd-serinedepressionl-serineNMDA receptor
Type
Short Communications
Information
Acta Neuropsychiatrica , Volume 28 , Issue 3 , June 2016 , pp. 173 - 178
Check for updates
Copyright
© Scandinavian College of Neuropsychopharmacology 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Sanacora, G, Zarate, CA, Krystal, JH, Manji, HK. Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nat Rev Drug Discov 2008;7:426–437.CrossRefGoogle ScholarPubMed
2. Hashimoto, K. Emerging role of glutamate in the pathophysiology of major depressive disorder. Brain Res Rev 2009;61:105–123.CrossRefGoogle ScholarPubMed
3. Hashimoto, K, Malchow, B, Faljai, P et al. Glutamate modulators as potential therapeutic drugs in schizophrenia and affective disorders. Eur Arch Psychiatry Clin Neurosci 2013;263:367–377.CrossRefGoogle ScholarPubMed
4. Krystal, JH, Sanacora, G, Duman, RS. Rapid-acting antidepressants: the path to ketamine and beyond. Biol Psychiatry 2013;73:1133–1141.CrossRefGoogle ScholarPubMed
5. Hashimoto, K. The R-stereoisomer of ketamine as an alternative for ketamine for treatment-resistant major depression. Clin Psychopharmacol Neurosci 2014;12:72–73.CrossRefGoogle ScholarPubMed
6. Yang, C, Hashimoto, K. Rapid antidepressant effects and abuse liability of ketamine. Psychopharmacology (Berl) 2014;231:2041–2042.CrossRefGoogle ScholarPubMed
7. Yang, C, Shirayama, Y, Zhang, JC et al. R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects. Transl Psychiatry 2015;5:e632.CrossRefGoogle ScholarPubMed
8. Heresco-Levy, U, Gelfin, G, Bloch, B et al. A randomized add-on trial of high-dose D-cycloserine for treatment-resistant depression. Int J Neuropsychopharmacol 2013;16:501–506.CrossRefGoogle ScholarPubMed
9. Hashimoto, K, Sawa, A, Iyo, M. Increased levels of glutamate in brains from patients with mood disorders. Biol Psychiatry 2007;62:1310–1316.CrossRefGoogle ScholarPubMed
10. Pålsson, E, Jakobsson, J, Södersten, K et al. Markers of glutamate signaling in cerebrospinal fluid and serum from patients with bipolar disorder and healthy controls. Eur Neuropsychopharmacol 2015;25:133–140.CrossRefGoogle ScholarPubMed
11. Hamilton, M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56–62.CrossRefGoogle ScholarPubMed
12. Ueda, N, Suda, A, Nakagawa, M et al. Reliability, validity and clinical utility of a Japanese version of the Social Adaptation Self-evaluation Scale as calibrated using the Beck Depression Inventory. Psychiatry Clin Neurosci 2011;65:624–629.CrossRefGoogle ScholarPubMed
13. Bosc, M. Assessment of social functioning in depression. Compr Psychiatry 2000;41:63–69.CrossRefGoogle ScholarPubMed
14. Yoshida, T, Suga, M, Arima, K et al. Criterion and construct validity of the CogState Schizophrenia Battery in Japanese patients with schizophrenia. PLoS One 2011;6:e20469.CrossRefGoogle ScholarPubMed
15. Yoshida, T, Ishikawa, M, Niitsu, T et al. Decreased serum levels of mature brain-derived neurotrophic factor (BDNF), but not its precursor proBDNF, in patients with major depressive disorder. PLoS One 2012;7:e42676.CrossRefGoogle Scholar
16. Fukushima, T, Kawai, J, Imai, K, Toyo'oka, T. Simultaneous determination of D- and L-serine in rat brain microdialysis sample using a column-switching HPLC with fluorimetric detection. Biomed Chromatogr 2004;18:813–819.CrossRefGoogle ScholarPubMed
17. Maes, M, De Backer, G, Suy, E, Minner, B. Increased plasma serine concentration in depression. Neuropsychobiology 1995;31:10–15.CrossRefGoogle ScholarPubMed
18. Sumiyoshi, T, Anil, AE, Jin, D et al. Plasma glycine and serine levels in schizophrenia compared to normal controls and major depression: relation to negative symptoms. Int J Neuropsychopharmacol 2004;7:1–8.CrossRefGoogle ScholarPubMed
19. Mitani, H, Shirayama, Y, Yamada, T et al. Correlation between plasma levels of glutamate, alanine and serine with severity of depression. Prog Neuropsychopharmacol Biol Psychiatry 2006;30:1155–1158.CrossRefGoogle ScholarPubMed
20. Altamura, C, Maes, M, Dai, J, Meltzer, HY. Plasma concentrations of excitatory amino acids, serine, glycine, taurine and histidine in major depression. Eur Neuropsychopharmacol 1995;5(Suppl.):71–75.CrossRefGoogle ScholarPubMed
21. Hashimoto, K. Targeting of NMDA receptors in new treatments of schizophrenia. Expert Opin Ther Targets 2014;18:1049–1063.CrossRefGoogle ScholarPubMed
22. Waziri, R, Mott, J, Wilcox, J. Differentiation of psychotic from nonpsychotic depression by a biological marker. J Affect Disord 1985;9:175–180.CrossRefGoogle ScholarPubMed
23. Hashimoto, K, Fukushima, T, Shimizu, E et al. 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.CrossRefGoogle ScholarPubMed
24. Moaddel, R, Luckenbaugh, DA, Xie, Y et al. D-serine plasma concentration is a potential biomarker of (R,S)-ketamine antidepressant response in subjects with treatment-resistant depression. Psychopharmacology (Berl) 2015;232:399–409.CrossRefGoogle ScholarPubMed
25. Hashimoto, K. Blood D-serine levels as a predictive biomarker for the rapid antidepressant effects of the NMDA receptor antagonist ketamine. Psychopharmacology (Berl) 2014;231:4081–4082.CrossRefGoogle ScholarPubMed
26. Hashimoto, K. Serine enantiomers as diagnostic biomarkers for schizophrenia and bipolar disorder. Eur Arch Psychiatry Clin Neurosci 2015; doi: 10.1007/s00406-015-0602-4.Google ScholarPubMed