The Role of Tryptophan Metabolites in Neuropsychiatric Disorders.

Majid Davidson, Niloufar Rashidi, Kulmira Nurgali, Vasso Apostolopoulos
Author Information
  1. Majid Davidson: Institute for Health and Sport, Victoria University, Melbourne, VIC 3011, Australia. ORCID
  2. Niloufar Rashidi: Institute for Health and Sport, Victoria University, Melbourne, VIC 3011, Australia.
  3. Kulmira Nurgali: Institute for Health and Sport, Victoria University, Melbourne, VIC 3011, Australia. ORCID
  4. Vasso Apostolopoulos: Institute for Health and Sport, Victoria University, Melbourne, VIC 3011, Australia. ORCID

Abstract

In recent decades, neuropsychiatric disorders such as major depressive disorder, schizophrenia, bipolar, etc., have become a global health concern, causing various detrimental influences on patients. Tryptophan is an important amino acid that plays an indisputable role in several physiological processes, including neuronal function and immunity. Tryptophan's metabolism process in the human body occurs using different pathways, including the kynurenine and serotonin pathways. Furthermore, other biologically active components, such as serotonin, melatonin, and niacin, are by-products of Tryptophan pathways. Current evidence suggests that a functional imbalance in the synthesis of Tryptophan metabolites causes the appearance of pathophysiologic mechanisms that leads to various neuropsychiatric diseases. This review summarizes the pharmacological influences of tryptophan and its metabolites on the development of neuropsychiatric disorders. In addition, tryptophan and its metabolites quantification following the neurotransmitters precursor are highlighted. Eventually, the efficiency of various biomarkers such as inflammatory, protein, electrophysiological, genetic, and proteomic biomarkers in the diagnosis/treatment of neuropsychiatric disorders was discussed to understand the biomarker application in the detection/treatment of various diseases.

Keywords

References

  1. FEBS J. 2015 Jul;282(14):2735-45 [PMID: 25950090]
  2. Neuropsychopharmacology. 2001 Aug;25(2):277-89 [PMID: 11425511]
  3. Public Health Nutr. 2004 Oct;7(7):959-63 [PMID: 15482625]
  4. Psychiatry Res. 2018 Nov;269:45-49 [PMID: 30145300]
  5. Psychiatry Clin Neurosci. 2020 Feb;74(2):112-117 [PMID: 31599111]
  6. Free Radic Biol Med. 2015 Dec;89:220-8 [PMID: 26393422]
  7. Pflugers Arch. 2011 Feb;461(2):211-23 [PMID: 21110037]
  8. J Clin Psychiatry. 2015 Feb;76(2):e199-206 [PMID: 25742207]
  9. Nat Commun. 2018 Aug 17;9(1):3294 [PMID: 30120222]
  10. J Psychopharmacol. 2009 May;23(3):287-94 [PMID: 18562404]
  11. Ann Neurol. 1992 Aug;32(2):198-206 [PMID: 1510359]
  12. J Mass Spectrom. 2006 Apr;41(4):517-26 [PMID: 16498605]
  13. BMJ. 2012 Dec 27;345:e8508 [PMID: 23271744]
  14. Behav Brain Funct. 2015 Nov 05;11(1):36 [PMID: 26542774]
  15. Rapid Commun Mass Spectrom. 2004;18(13):1413-20 [PMID: 15216500]
  16. J Affect Disord. 2015 Feb 1;172:81-8 [PMID: 25451399]
  17. Mol Psychiatry. 2020 Jan;25(1):131-147 [PMID: 30980044]
  18. Neurosci Biobehav Rev. 2009 Jun;33(6):926-52 [PMID: 19428501]
  19. Clin Pract Epidemiol Ment Health. 2020 Jul 30;16(Suppl-1):156-164 [PMID: 33029192]
  20. Amino Acids. 2013 Dec;45(6):1319-29 [PMID: 24105077]
  21. Clin Pharmacol Ther. 2001 Mar;69(3):89-95 [PMID: 11240971]
  22. Gene. 2013 Oct 10;528(2):320-7 [PMID: 23872233]
  23. Sci Rep. 2020 Nov 6;10(1):19280 [PMID: 33159145]
  24. Clin Nutr. 2019 Oct;38(5):1995-2001 [PMID: 30497694]
  25. Molecules. 2018 Apr 02;23(4): [PMID: 29614844]
  26. Psychiatr Danub. 2017 Dec;29(4):394-400 [PMID: 29197195]
  27. Psychiatr Q. 2012 Mar;83(1):91-102 [PMID: 21877216]
  28. Exp Mol Med. 2014 Nov 14;46:e121 [PMID: 25394548]
  29. J Affect Disord. 2010 Nov;126(3):366-87 [PMID: 20541810]
  30. Prog Neuropsychopharmacol Biol Psychiatry. 2011 Apr 29;35(3):702-21 [PMID: 21185346]
  31. Biol Psychiatry. 2005 Jun 1;57(11):1215-20 [PMID: 15949990]
  32. Adv Pharmacol. 2016;76:13-37 [PMID: 27288072]
  33. J Chromatogr A. 2016 Feb 19;1434:91-101 [PMID: 26818237]
  34. Eur J Pharmacol. 1981 Jul 10;72(4):411-2 [PMID: 6268428]
  35. Biol Psychiatry. 1973 Apr;6(2):109-18 [PMID: 4709128]
  36. J Neurochem. 2001 Aug;78(4):842-53 [PMID: 11520905]
  37. Plant J. 2021 Jan;105(2):376-391 [PMID: 32645752]
  38. Int J Mol Sci. 2021 May 08;22(9): [PMID: 34066870]
  39. Clin J Pain. 2011 Jul-Aug;27(6):529-34 [PMID: 21415718]
  40. Front Immunol. 2021 May 19;12:667179 [PMID: 34093561]
  41. J Affect Disord. 2016 Sep 15;202:120-3 [PMID: 27262632]
  42. Am J Psychiatry. 1983 Jun;140(6):757-60 [PMID: 6405638]
  43. In Vivo. 2014 Jul-Aug;28(4):633-8 [PMID: 24982234]
  44. J Cell Physiol. 2015 Aug;230(8):1822-8 [PMID: 25522009]
  45. J Clin Psychiatry. 2014 Sep;75(9):e906-15 [PMID: 25295433]
  46. Int J Neurosci. 1992 Nov-Dec;67(1-4):127-44 [PMID: 1305630]
  47. Am J Psychiatry. 2016 Jun 1;173(6):575-87 [PMID: 27113121]
  48. Int J Neuropsychopharmacol. 2014 Oct;17(10):1599-608 [PMID: 24901538]
  49. BMC Nephrol. 2016 Nov 10;17(1):171 [PMID: 27832762]
  50. Neuropsychopharmacology. 2002 Oct;27(4):672-83 [PMID: 12377404]
  51. J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Sep 15;879(26):2720-5 [PMID: 21855425]
  52. Psychol Med. 1976 Nov;6(4):673-8 [PMID: 794897]
  53. Schizophr Bull. 1984;10(1):30-48 [PMID: 6142525]
  54. Behav Brain Funct. 2008 Oct 20;4:48 [PMID: 18937842]
  55. Curr Psychiatry Rep. 2013 Dec;15(12):425 [PMID: 24243532]
  56. J Psychopharmacol. 2012 May;26(5):629-35 [PMID: 22158544]
  57. PLoS One. 2020 Jun 18;15(6):e0233850 [PMID: 32555730]
  58. Sci Rep. 2020 Sep 28;10(1):15908 [PMID: 32985599]
  59. Eur J Clin Nutr. 2010 Aug;64(8):832-9 [PMID: 20485303]
  60. Int J Mol Sci. 2021 Jun 28;22(13): [PMID: 34203517]
  61. Schizophr Res. 2019 Jun;208:439-440 [PMID: 30962118]
  62. Neural Plast. 2016;2016:9162590 [PMID: 27843651]
  63. Clin Psychopharmacol Neurosci. 2020 Nov 30;18(4):507-526 [PMID: 33124585]
  64. Front Psychiatry. 2021 May 12;12:649833 [PMID: 34054609]
  65. Neuropsychopharmacology. 2016 Sep;41(10):2587-95 [PMID: 27143602]
  66. J Neural Transm (Vienna). 2022 Apr;129(4):361-377 [PMID: 35286460]
  67. Int J Tryptophan Res. 2019 Jun 19;12:1178646919852996 [PMID: 31258331]
  68. Int J Mol Sci. 2021 Mar 15;22(6): [PMID: 33804088]
  69. Prog Neuropsychopharmacol Biol Psychiatry. 2021 Jan 10;104:110051 [PMID: 32758517]
  70. Psychopharmacologia. 1974 Jan 9;34(1):11-20 [PMID: 4593517]
  71. J Infect Dis. 2003 Sep 15;188(6):844-9 [PMID: 12964115]
  72. Toxins (Basel). 2018 Jan 08;10(1): [PMID: 29316724]
  73. Transl Psychiatry. 2021 Apr 1;11(1):198 [PMID: 33795641]
  74. J Psychiatry Neurosci. 2014 Jan;39(1):6-21 [PMID: 23971978]
  75. Benef Microbes. 2017 Apr 26;8(2):153-162 [PMID: 28443383]
  76. Neuropharmacology. 2017 Jan;112(Pt B):237-247 [PMID: 27511838]
  77. J Psychopharmacol. 2013 Oct;27(10):878-93 [PMID: 23904410]
  78. Curr Pharm Des. 2016;22(8):949-54 [PMID: 26654774]
  79. Lancet. 1963 Jan 12;1(7272):79-81 [PMID: 14022907]
  80. Prim Care Companion CNS Disord. 2021 Jan 21;23(1): [PMID: 33480483]
  81. Curr Pharm Des. 2016;22(8):987-1012 [PMID: 26654772]
  82. Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12553-8 [PMID: 8901620]
  83. Biol Psychiatry. 1998 Aug 1;44(3):151-62 [PMID: 9693387]
  84. Pak J Pharm Sci. 2021 Jul;34(4(Supplementary)):1499-1508 [PMID: 34799325]
  85. Curr Neuropharmacol. 2018;16(5):574-582 [PMID: 28901278]
  86. Expert Opin Ther Targets. 2019 Aug;23(8):655-667 [PMID: 31216212]
  87. J Infect Dis. 2019 Jun 5;220(1):127-138 [PMID: 30721966]
  88. Schizophr Res. 2015 Dec;169(1-3):491-493 [PMID: 26547882]
  89. Psychoneuroendocrinology. 2014 Jul;45:202-10 [PMID: 24845191]
  90. Nat Rev Neurosci. 2012 Jul;13(7):465-77 [PMID: 22678511]
  91. J Psychiatry Neurosci. 1991 Dec;16(5):241-6 [PMID: 1797098]
  92. Postgrad Med. 2010 Nov;122(6):107-16 [PMID: 21084787]
  93. Antioxidants (Basel). 2021 Nov 10;10(11): [PMID: 34829665]
  94. J Pineal Res. 2019 Apr;66(3):e12544 [PMID: 30586215]
  95. J Psychiatry Neurosci. 2015 Mar;40(2):126-33 [PMID: 25455350]
  96. Pharmacol Res. 2011 Jan;63(1):85-92 [PMID: 20940053]
  97. Front Endocrinol (Lausanne). 2019 Mar 01;10:87 [PMID: 30881340]
  98. Schizophr Bull. 2014 Jul;40(4):721-8 [PMID: 24870447]
  99. eNeurologicalSci. 2020 Sep 10;21:100270 [PMID: 33134567]
  100. Exp Gerontol. 2020 Jan;129:110770 [PMID: 31704347]
  101. Curr Drug Targets. 2013 May 1;14(5):571-7 [PMID: 23531160]
  102. Neural Regen Res. 2017 Jan;12(1):64-65 [PMID: 28250745]
  103. Br J Psychiatry. 2001 May;178:399-405 [PMID: 11331552]
  104. J Neural Transm (Vienna). 2008 Dec;115(12):1687-94 [PMID: 18982242]
  105. Wound Repair Regen. 2019 Jul;27(4):375-385 [PMID: 31017740]
  106. Br J Pharmacol. 2016 Sep;173(18):2702-25 [PMID: 27314810]
  107. Int J Tryptophan Res. 2016 Oct 26;9:79-88 [PMID: 27812290]
  108. Neurosci Biobehav Rev. 2010 Mar;34(3):387-407 [PMID: 19715722]
  109. Neurosci Biobehav Rev. 2018 Jul;90:212-220 [PMID: 29656032]
  110. Prog Neuropsychopharmacol Biol Psychiatry. 2016 Oct 3;70:8-16 [PMID: 27117820]
  111. Neuropharmacology. 2017 Jan;112(Pt B):248-263 [PMID: 26617070]
  112. Prog Neuropsychopharmacol Biol Psychiatry. 2010 Oct 1;34(7):1279-84 [PMID: 20643177]
  113. Sci Rep. 2020 Feb 6;10(1):2049 [PMID: 32029799]
  114. Eur J Clin Nutr. 2007 Mar;61(3):355-61 [PMID: 17151594]
  115. J Affect Disord. 2017 Nov;222:32-39 [PMID: 28668713]
  116. Int J Tryptophan Res. 2009;2:1-19 [PMID: 22084578]
  117. Curr Drug Targets. 2013 May 1;14(5):514-21 [PMID: 23514379]
  118. Acta Vitaminol Enzymol. 1978;32(5-6):188-94 [PMID: 583200]
  119. Nutr Rev. 2022 Jan 10;80(2):306-316 [PMID: 33942088]
  120. Adv Clin Chem. 2020;95:165-218 [PMID: 32122523]
  121. Diabetes. 2018 Sep;67(9):1858-1866 [PMID: 29945890]
  122. J Psychiatr Res. 2017 Feb;85:1-14 [PMID: 27814455]
  123. Curr Opin Psychiatry. 2019 Sep;32(5):394-401 [PMID: 31192814]
  124. Brain Connect. 2021 May;11(4):253-263 [PMID: 33403915]
  125. Infect Immun. 2005 Aug;73(8):5249-51 [PMID: 16041050]
  126. Sci Rep. 2018 Jul 19;8(1):10965 [PMID: 30026567]
  127. J Psychiatr Res. 2012 Feb;46(2):198-204 [PMID: 22094284]
  128. PLoS One. 2013 Oct 16;8(10):e78146 [PMID: 24147117]
  129. Nat Rev Drug Discov. 2019 May;18(5):379-401 [PMID: 30760888]
  130. Electrophoresis. 2018 May;39(9-10):1171-1180 [PMID: 29327354]
  131. Neurosci Biobehav Rev. 2018 Sep;92:477-485 [PMID: 29940237]
  132. Int J Tryptophan Res. 2017 Mar 15;10:1178646917691938 [PMID: 28469468]
  133. Cell. 2015 Apr 9;161(2):264-76 [PMID: 25860609]
  134. Neuropharmacology. 2017 Jan;112(Pt B):324-330 [PMID: 26820800]
  135. Med Hypotheses. 2021 Aug;153:110627 [PMID: 34139598]
  136. Pharmacopsychiatry. 1987 Nov;20(6):245-8 [PMID: 3432358]
  137. Fundam Clin Pharmacol. 2021 Feb;35(1):25-39 [PMID: 32415694]
  138. Brain Behav Immun. 2011 Jul;25(5):932-7 [PMID: 20951792]
  139. Psychopharmacology (Berl). 1986;89(1):1-7 [PMID: 3090582]
  140. Trends Pharmacol Sci. 2008 Sep;29(9):433-6 [PMID: 18585794]
  141. Neurosci Biobehav Rev. 2018 Jul;90:50-69 [PMID: 29608989]
  142. Front Endocrinol (Lausanne). 2019 Apr 08;10:158 [PMID: 31024440]
  143. Exp Mol Med. 2019 Jan 7;51(1):1-10 [PMID: 30613102]
  144. World J Biol Psychiatry. 2016 Oct;17(7):535-46 [PMID: 26068130]
  145. Oxid Med Cell Longev. 2018 Nov 21;2018:8604718 [PMID: 30584466]
  146. Am J Clin Nutr. 1958 Sep-Oct;6(5):479-86 [PMID: 13594872]
  147. Child Adolesc Psychiatry Ment Health. 2021 Aug 31;15(1):44 [PMID: 34465371]
  148. Sci Rep. 2021 Jan 29;11(1):2649 [PMID: 33514851]
  149. Front Immunol. 2021 Jun 04;12:653208 [PMID: 34149693]
  150. Trends Pharmacol Sci. 2018 Jun;39(6):560-572 [PMID: 29628275]
  151. Int J Tryptophan Res. 2017 Mar 10;10:1178646917694600 [PMID: 28469469]
  152. Curr Med Chem. 2018;25(32):3866-3882 [PMID: 28183259]
  153. Front Psychiatry. 2016 Apr 25;7:72 [PMID: 27199779]
  154. Brain Behav Immun. 2016 Jan;51:47-55 [PMID: 26189678]
  155. Schizophr Res. 2015 Jul;165(2-3):188-94 [PMID: 25956633]
  156. Front Psychiatry. 2020 Feb 26;11:71 [PMID: 32174850]
  157. Biol Psychiatry. 1983 May;18(5):575-8 [PMID: 6860730]
  158. J Histochem Cytochem. 2010 Jan;58(1):17-28 [PMID: 19741271]
  159. Prev Nutr Food Sci. 2016 Dec;21(4):297-309 [PMID: 28078251]
  160. Science. 2005 Nov 4;310(5749):850-5 [PMID: 16272121]
  161. Expert Rev Neurother. 2009 Apr;9(4):461-76 [PMID: 19344299]
  162. Curr Top Med Chem. 2018;18(19):1704-1715 [PMID: 30430940]
  163. J Neurochem. 1990 Mar;54(3):783-6 [PMID: 1689378]
  164. PLoS One. 2011;6(6):e20304 [PMID: 21673801]
  165. Nutr Neurosci. 2020 Dec;23(12):983-992 [PMID: 30794085]
  166. Brain Behav Immun. 2002 Oct;16(5):590-5 [PMID: 12401473]
  167. ACS Chem Neurosci. 2017 May 17;8(5):961-972 [PMID: 28378993]
  168. Amino Acids. 1996 Mar;10(1):21-47 [PMID: 24178430]
  169. Cytokine Growth Factor Rev. 2021 Jun;59:111-117 [PMID: 33658144]
  170. Schizophr Res. 2017 Nov;189:208-209 [PMID: 28162810]
  171. Science. 1971 Jul 9;173(3992):149-52 [PMID: 5581909]
  172. J Psychiatr Res. 2018 May;100:24-32 [PMID: 29475018]
  173. Mol Psychiatry. 2011 Mar;16(3):252-64 [PMID: 20661246]
  174. Psychoneuroendocrinology. 2019 Feb;100:213-222 [PMID: 30388595]
  175. Psychiatry Res. 2021 Sep;303:114060 [PMID: 34175711]

MeSH Term

Depressive Disorder, Major
Humans
Kynurenine
Proteomics
Serotonin
Tryptophan

Chemicals

Serotonin
Kynurenine
Tryptophan

Word Cloud

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