Table Info

Table 1.

Stress and inflammation in depressive episode subtypes and pain

Features	Melancholic episode	Atypical episode	Pain
Mood	Flat, anhedonia	Reactive	-
Worsening of mood	Morning	Evening	-
Insomnia	Early awakening	Hypersomnia	Insomnia
Eating behavior	Hyporexia	Craving for carbohydrates	-
Activity	Slowdown	Leaden paralysis	Fatigue
Innate immunity	↑	↑	↑
Adaptive immunity	↑	↑	↑
TNF-α	↑	↑	↑
IL-1	↑	↑	↑
IL-6	↑	-	↑
CRP	↑	-	↑
BBB	Decreased	-	-
DexST	Suppressed	Normal	Normal
SNS	↑	-	↑
CRF	↑	↓	-
ACTH	↑	↓	Normal stress stimulus response
Cortisol	↑ at basal level	Reduced production	Blunted stress stimulus response
KYN	↑	-	↑
5HT	↓	↓	↓
GABA	↓	-	↓
BDNF	↓	↓	↓

↑: hyperactivity or increased level; ↓: hypoactivity or decreased level; -: no date. TNF-α: tumor necrosis factor-α; IL-1: interleukin-1; CRP: C-reactive protein; BBB: blood-brain barrier; DexST: dexamethasone suppression test; SNS: sympathetic nervous system; CRF: corticotropin-releasing factor; ACTH: adrenocorticotropic hormone; KYN: kynurenine; 5HT: serotonin; GABA: gamma-aminobutyric acid; BDNF: brain-derived neurotrophic factor

Declarations

Author contributions

AC: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. GC: Writing—original draft, Validation, Writing—review & editing, Supervision. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

References

Meda RT, Nuguru SP, Rachakonda S, Sripathi S, Khan MI, Patel N. Chronic Pain-Induced Depression: A Review of Prevalence and Management. Cureus. 2022;14:e28416. [DOI] [PubMed] [PMC]

Turvey SE, Broide DH. Innate immunity. J Allergy Clin Immunol. 2010;125:S24–32. [DOI] [PubMed] [PMC]

Bonilla FA, Oettgen HC. Adaptive immunity. J Allergy Clin Immunol. 2010;125:S33–40. [DOI] [PubMed]

Baral P, Udit S, Chiu IM. Pain and immunity: implications for host defence. Nat Rev Immunol. 2019;19:433–47. [DOI] [PubMed] [PMC]

Karin M. Nuclear factor-κB in cancer development and progression. Nature. 2006;441:431–6. [DOI] [PubMed]

Kawai T, Akira S. Antiviral signaling through pattern recognition receptors. J Biochem. 2007;141:137–45. [DOI] [PubMed]

Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006;27:24–31. [DOI] [PubMed] [PMC]

Curfs JH, Meis JF, Hoogkamp-Korstanje JA. A primer on cytokines: sources, receptors, effects, and inducers. Clin Microbiol Rev. 1997;10:742–80. [DOI] [PubMed] [PMC]

Murphy K. Janeway’s immunobiology. New York, NY: Garland Science; 2011.

10.

Debnath M, Doyle K, Langan C, McDonald C, Leonard B, Cannon D. Recent advances in psychoneuroimmunology: Inflammation in psychiatric disorders. Transl Neurosci. 2011;2:121–37. [DOI]

11.

Rosenberger PH, Ickovics JR, Epel E, Nadler E, Jokl P, Fulkerson JP, et al. Surgical stress-induced immune cell redistribution profiles predict short-term and long-term postsurgical recovery: A prospective study. J Bone Joint Surg Am. 2009;91:2783–94. [DOI] [PubMed] [PMC]

12.

Slavich GM, Cole SW. The Emerging Field of Human Social Genomics. Clin Psychol Sci. 2013;1:331–48. [DOI] [PubMed] [PMC]

13.

Irwin MR, Cole SW. Reciprocal regulation of the neural and innate immune systems. Nat Rev Immunol. 2011;11:625–32. [DOI] [PubMed] [PMC]

14.

Tracey KJ. Reflex control of immunity. Nat Rev Immunol. 2009;9:418–28. [DOI] [PubMed] [PMC]

15.

Cole SW. Elevating the perspective on human stress genomics. Psychoneuroendocrinology. 2010;35:955–62. [DOI] [PubMed] [PMC]

16.

Duman RS, Aghajanian GK. Synaptic dysfunction in depression: potential therapeutic targets. Science. 2012;338:68–72. [DOI] [PubMed] [PMC]

17.

Miller GE, Cohen S, Ritchey AK. Chronic psychological stress and the regulation of pro-inflammatory cytokines: a glucocorticoid-resistance model. Health Psychol. 2002;21:531–41. [DOI] [PubMed]

18.

Schleimer RP. An overview of glucocorticoid anti-inflammatory actions. Eur J Clin Pharmacol. 1993;45:S3–7. [DOI] [PubMed]

19.

Dickerson SS, Gable SL, Irwin MR, Aziz N, Kemeny ME. Social-evaluative threat and proinflammatory cytokine regulation: an experimental laboratory investigation. Psychol Sci. 2009;20:1237–44. [DOI] [PubMed] [PMC]

20.

Pace TW, Hu F, Miller AH. Cytokine-effects on glucocorticoid receptor function: relevance to glucocorticoid resistance and the pathophysiology and treatment of major depression. Brain Behav Immun. 2007;21:9–19. [DOI] [PubMed] [PMC]

21.

Green PG, Alvarez P, Levine JD. Sexual dimorphic role of the glucocorticoid receptor in chronic muscle pain produced by early-life stress. Mol Pain. 2021;17:17448069211011313. [DOI] [PubMed] [PMC]

22.

Ivy AS, Brunson KL, Sandman C, Baram TZ. Dysfunctional nurturing behavior in rat dams with limited access to nesting material: a clinically relevant model for early-life stress. Neuroscience. 2008;154:1132–42. [DOI] [PubMed] [PMC]

23.

Waller R, Smith AJ, O’Sullivan PB, Slater H, Sterling M, Straker LM. The association of early life stressors with pain sensitivity and pain experience at 22 years. Pain. 2020;161:220–9. [DOI] [PubMed]

24.

Melchior M, Kuhn P, Poisbeau P. The burden of early life stress on the nociceptive system development and pain responses. Eur J Neurosci. 2022;55:2216–41. [DOI] [PubMed]

25.

Park C, Rosenblat JD, Brietzke E, Pan Z, Lee Y, Cao B, et al. Stress, epigenetics and depression: A systematic review. Neurosci Biobehav Rev. 2019;102:139–52. [DOI] [PubMed]

26.

McEwen BS. Protective and damaging effects of stress mediators. N Engl J Med. 1998;338:171–9. [DOI] [PubMed]

27.

Hodes GE, Kana V, Menard C, Merad M, Russo SJ. Neuroimmune mechanisms of depression. Nat Neurosci. 2015;18:1386–93. [DOI] [PubMed] [PMC]

28.

Pfau ML, Russo SJ. Peripheral and Central Mechanisms of Stress Resilience. Neurobiol Stress. 2015;1:66–79. [DOI] [PubMed] [PMC]

29.

Ménard C, Pfau ML, Hodes GE, Russo SJ. Immune and Neuroendocrine Mechanisms of Stress Vulnerability and Resilience. Neuropsychopharmacology. 2017;42:62–80. [DOI] [PubMed] [PMC]

30.

Raja SN, Carr DB, Cohen M, Finnerup NB, Flor H, Gibson S, et al. The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises. Pain. 2020;161:1976–82. [DOI] [PubMed] [PMC]

31.

Dubin AE, Patapoutian A. Nociceptors: the sensors of the pain pathway. J Clin Invest. 2010;120:3760–72. [DOI] [PubMed] [PMC]

32.

Liu XJ, Zhang Y, Liu T, Xu ZZ, Park CK, Berta T, et al. Nociceptive neurons regulate innate and adaptive immunity and neuropathic pain through MyD88 adapter. Cell Res. 2014;24:1374–7. [DOI] [PubMed] [PMC]

33.

Sorge RE, Mapplebeck JC, Rosen S, Beggs S, Taves S, Alexander JK, et al. Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat Neurosci. 2015;18:1081–3. [DOI] [PubMed] [PMC]

34.

Marichal-Cancino BA, González-Hernández A, Muñoz-Islas E, Villalón CM. Monoaminergic Receptors as Modulators of the Perivascular Sympathetic and Sensory CGRPergic Outflows. Curr Neuropharmacol. 2020;18:790–808. [DOI] [PubMed] [PMC]

35.

Panchal NK, Prince Sabina E. Non-steroidal anti-inflammatory drugs (NSAIDs): A current insight into its molecular mechanism eliciting organ toxicities. Food Chem Toxicol. 2023;172:113598. [DOI] [PubMed]

36.

Pinho-Ribeiro FA, Verri WA Jr, Chiu IM. Nociceptor Sensory Neuron–Immune Interactions in Pain and Inflammation. Trends Immunol. 2017;38:5–19. [DOI] [PubMed] [PMC]

37.

De Sordi L, Lourenço M, Debarbieux L. The Battle Within: Interactions of Bacteriophages and Bacteria in the Gastrointestinal Tract. Cell Host Microbe. 2019;25:210–8. [DOI] [PubMed]

38.

Flint HJ, Bayer EA, Rincon MT, Lamed R, White BA. Polysaccharide utilization by gut bacteria: potential for new insights from genomic analysis. Nat Rev Microbiol. 2008;6:121–31. [DOI] [PubMed]

39.

Parada Venegas D, De la Fuente MK, Landskron G, González MJ, Quera R, Dijkstra G, et al. Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases. Front Immunol. 2019;10:277. [DOI] [PubMed] [PMC]

40.

Dalile B, Van Oudenhove L, Vervliet B, Verbeke K. The role of short-chain fatty acids in microbiota–gut–brain communication. Nat Rev Gastroenterol Hepatol. 2019;16:461–78. [DOI] [PubMed]

41.

van Thiel IAM, Botschuijver S, de Jonge WJ, Seppen J. Painful interactions: Microbial compounds and visceral pain. Biochim Biophys Acta Mol Basis Dis. 2020;1866:165534. [DOI] [PubMed]

42.

Russo R, De Caro C, Avagliano C, Cristiano C, La Rana G, Mattace Raso G, et al. Sodium butyrate and its synthetic amide derivative modulate nociceptive behaviors in mice. Pharmacol Res. 2016;103:279–91. [DOI] [PubMed]

43.

Long X, Li M, Li LX, Sun YY, Zhang WX, Zhao DY, et al. Butyrate promotes visceral hypersensitivity in an IBS-like model via enteric glial cell-derived nerve growth factor. Neurogastroenterol Motil. 2018;30:e13227. [DOI] [PubMed]

44.

Heuberger DM, Schuepbach RA. Protease-activated receptors (PARs): mechanisms of action and potential therapeutic modulators in PAR-driven inflammatory diseases. Thromb J. 2019;17:4. [DOI] [PubMed] [PMC]

45.

Jacob C, Yang PC, Darmoul D, Amadesi S, Saito T, Cottrell GS, et al. Mast cell tryptase controls paracellular permeability of the intestine. Role of protease-activated receptor 2 and β-arrestins. J Biol Chem. 2005;280:31936–48. [DOI] [PubMed]

46.

Hoshino K, Takeuchi O, Kawai T, Sanjo H, Ogawa T, Takeda Y, et al. Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J Immunol. 1999;162:3749–52. [PubMed]

47.

American Psychiatric Association. Desk Reference to the Diagnostic Criteria from DSM-5. Arlington: American Psychiatric Association; 2016.

48.

Fink M, Bolwig TG, Parker G, Shorter E. Melancholia: restoration in psychiatric classification recommended. Acta Psychiatr Scand. 2007;115:89–92. [DOI] [PubMed] [PMC]

49.

Tondo L, Vázquez GH, Baldessarini RJ. Melancholic versus Nonmelancholic Major Depression Compared. J Affect Disord. 2020;266:760–5. [DOI] [PubMed]

50.

Parker G, Fink M, Shorter E, Taylor MA, Akiskal H, Berrios G, et al. Issues for DSM-5: whither melancholia? The case for its classification as a distinct mood disorder. Am J Psychiatry. 2010;167:745–7. [DOI] [PubMed] [PMC]

51.

Gama Marques J, Ouakinin S. Schizophrenia–schizoaffective–bipolar spectra: an epistemological perspective. CNS Spectr. 2021;26:197–201. [DOI] [PubMed]

52.

Carroll BJ. The dexamethasone suppression test for melancholia. Br J Psychiatry. 1982;140:292–304. [DOI] [PubMed]

53.

Schumacher MM, Santambrogio J. Cortisol and the Dexamethasone Suppression Test as a Biomarker for Melancholic Depression: A Narrative Review. J Pers Med. 2023;13:837. [DOI] [PubMed] [PMC]

54.

Carroll BJ, Feinberg M, Greden JF, Tarika J, Albala AA, Haskett RF, et al. A specific laboratory test for the diagnosis of melancholia. Standardization, validation, and clinical utility. Arch Gen Psychiatry. 1981;38:15–22. [DOI] [PubMed]

55.

Kannan CR. Clinical Surveys in Endocrinology. In: The Pituitary Gland. New York, NY: Springer; 1987.

56.

Paslakis G, Krumm B, Gilles M, Schweiger U, Heuser I, Richter I, et al. Discrimination between patients with melancholic depression and healthy controls: comparison between 24-h cortisol profiles, the DST and the Dex/CRH test. Psychoneuroendocrinology. 2011;36:691–8. [DOI] [PubMed]

57.

The dexamethasone suppression test: an overview of its current status in psychiatry. The APA Task Force on Laboratory Tests in Psychiatry. Am J Psychiatry. 1987;144:1253–62. [DOI] [PubMed]

58.

Insel TR, Goodwin FK. The dexamethasone suppression test: promises and problems of diagnostic laboratory tests in psychiatry. Hosp Community Psychiatry. 1983;34:1131–8. [DOI] [PubMed]

59.

Slavich GM, Irwin MR. From stress to inflammation and major depressive disorder: a social signal transduction theory of depression. Psychol Bull. 2014;140:774–815. [DOI] [PubMed] [PMC]

60.

Klein DF, Davis JM. Diagnosis and Drug Treatment of Psychiatric Disorders. Baltimore: Williams & Wilkins; 1969. pp. 24.

61.

Juruena MF, Bocharova M, Agustini B, Young AH. Atypical depression and non-atypical depression: Is HPA axis function a biomarker? A systematic review. J Affect Disord. 2018;233:45–67. [DOI] [PubMed]

62.

Woelfer M, Kasties V, Kahlfuss S, Walter M. The Role of Depressive Subtypes within the Neuroinflammation Hypothesis of Major Depressive Disorder. Neuroscience. 2019;403:93–110. [DOI] [PubMed]

63.

Gold PW. The organization of the stress system and its dysregulation in depressive illness. Mol Psychiatry. 2015;20:32–47. [DOI] [PubMed]

64.

Eisenberger NI, Inagaki TK, Rameson LT, Mashal NM, Irwin MR. An fMRI study of cytokine-induced depressed mood and social pain: the role of sex differences. Neuroimage. 2009;47:881–90. [DOI] [PubMed] [PMC]

65.

Handwerger K. Differential patterns of HPA activity and reactivity in adult posttraumatic stress disorder and major depressive disorder. Harv Rev Psychiatry. 2009;17:184–205. [DOI] [PubMed]

66.

Perugi G, Fornaro M, Akiskal HS. Are atypical depression, borderline personality disorder and bipolar II disorder overlapping manifestations of a common cyclothymic diathesis? World Psychiatry. 2011;10:45–51. [DOI] [PubMed] [PMC]

67.

Ross RL, Jones KD, Ward RL, Wood LJ, Bennett RM. Atypical depression is more common than melancholic in fibromyalgia: an observational cohort study. BMC Musculoskelet Disord. 2010;11:120. [DOI] [PubMed] [PMC]

68.

Wohleb ES, Hanke ML, Corona AW, Powell ND, Stiner LM, Bailey MT, et al. β-Adrenergic receptor antagonism prevents anxiety-like behavior and microglial reactivity induced by repeated social defeat. J Neurosci. 2011;31:6277–88. [DOI] [PubMed] [PMC]

69.

Beurel E, Toups M, Nemeroff CB. The Bidirectional Relationship of Depression and Inflammation: Double Trouble. Neuron. 2020;107:234–56. [DOI] [PubMed] [PMC]

70.

Oukka M, Bettelli E. Regulation of lymphocyte trafficking in central nervous system autoimmunity. Curr Opin Immunol. 2018;55:38–43. [DOI] [PubMed] [PMC]

71.

Björkholm C, Monteggia LM. BDNF – a key transducer of antidepressant effects. Neuropharmacology. 2016;102:72–9. [DOI] [PubMed] [PMC]

72.

Porter GA, O’Connor JC. Brain-derived neurotrophic factor and inflammation in depression: Pathogenic partners in crime? World J Psychiatry. 2022;12:77–97. [DOI] [PubMed] [PMC]

73.

Xu D, Gao LN, Song XJ, Dong QW, Chen YB, Cui YL, et al. Enhanced antidepressant effects of BDNF-quercetin alginate nanogels for depression therapy. J Nanobiotechnology. 2023;21:379. [DOI] [PubMed] [PMC]

74.

Duman RS, Monteggia LM. A neurotrophic model for stress-related mood disorders. Biol Psychiatry. 2006;59:1116–27. [DOI] [PubMed]

75.

Schmidt HD, Duman RS. Peripheral BDNF produces antidepressant-like effects in cellular and behavioral models. Neuropsychopharmacology. 2010;35:2378–91. [DOI] [PubMed] [PMC]

76.

Autry AE, Adachi M, Nosyreva E, Na ES, Los MF, Cheng P, et al. NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature. 2011;475:91–5. [DOI] [PubMed] [PMC]

77.

Turkheimer FE, Veronese M, Mondelli V, Cash D, Pariante CM. Sickness behaviour and depression: An updated model of peripheral-central immunity interactions. Brain Behav Immun. 2023;111:202–10. [DOI] [PubMed]

78.

Enache D, Pariante CM, Mondelli V. Markers of central inflammation in major depressive disorder: A systematic review and meta-analysis of studies examining cerebrospinal fluid, positron emission tomography and post-mortem brain tissue. Brain Behav Immun. 2019;81:24–40. [DOI] [PubMed]

79.

Dunjic-Kostic B, Ivkovic M, Radonjic NV, Petronijevic ND, Pantovic M, Damjanovic A, et al. Melancholic and atypical major depression — Connection between cytokines, psychopathology and treatment. Prog Neuropsychopharmacol Biol Psychiatry. 2013;43:1–6. [DOI] [PubMed]

80.

Goshen I, Kreisel T, Ounallah-Saad H, Renbaum P, Zalzstein Y, Ben-Hur T, et al. A dual role for interleukin-1 in hippocampal-dependent memory processes. Psychoneuroendocrinology. 2007;32:1106–15. [DOI] [PubMed]

81.

Ettman CK, Abdalla SM, Cohen GH, Sampson L, Vivier PM, Galea S. Prevalence of Depression Symptoms in US Adults Before and During the COVID-19 Pandemic. JAMA Netw Open. 2020;3:e2019686. [DOI] [PubMed] [PMC]

82.

Ciaramella A, Poli P. Assessment of depression among cancer patients: the role of pain, cancer type and treatment. Psychooncology. 2001;10:156–65. [DOI] [PubMed]

83.

Rossi M, Jarego M, Ferreira-Valente A, Miró J, Sánchez-Rodríguez E, Ciaramella A. A biopsychosocial perspective of mental health risk in Italy during phase two of the COVID-19 lockdown. Anal Psicol. 2023;41:143–59. [DOI]

84.

Benedetti F, Palladini M, Paolini M, Melloni E, Vai B, Lorenzo RD, et al. Brain correlates of depression, post-traumatic distress, and inflammatory biomarkers in COVID-19 survivors: A multimodal magnetic resonance imaging study. Brain Behav Immun Health. 2021;18:100387. [DOI] [PubMed] [PMC]

85.

Dworkin RH, Gitlin MJ. Clinical aspects of depression in chronic pain patients. Clin J Pain. 1991;7:79–94. [DOI] [PubMed]

86.

Zheng CJ, Van Drunen S, Egorova-Brumley N. Neural correlates of co-occurring pain and depression: an activation-likelihood estimation (ALE) meta-analysis and systematic review. Transl Psychiatry. 2022;12:196. [DOI] [PubMed] [PMC]

87.

Ciaramella A. Psychopharmacology of chronic pain. Handb Clin Neurol. 2019;165:317–37. [DOI] [PubMed]

88.

Polatin PB, Kinney RK, Gatchel RJ, Lillo E, Mayer TG. Psychiatric illness and chronic low-back pain. The mind and the spine—which goes first? Spine (Phila Pa 1976). 1993;18:66–71. [DOI] [PubMed]

89.

Ciaramella A. Mood Spectrum Disorders and Perception of Pain. Psychiatr Q. 2017;88:687–700. [DOI] [PubMed]

90.

Korniloff K, Kotiaho S, Vanhala M, Kautiainen H, Koponen H, Mäntyselkä P. Musculoskeletal Pain in Melancholic and Atypical Depression. Pain Med. 2017;18:341–7. [DOI] [PubMed]

91.

Ebbinghaus M, Uhlig B, Richter F, von Banchet GS, Gajda M, Bräuer R, et al. The role of interleukin-1β in arthritic pain: main involvement in thermal, but not mechanical, hyperalgesia in rat antigen-induced arthritis. Arthritis Rheum. 2012;64:3897–907. [DOI] [PubMed]

92.

Afari N, Ahumada SM, Wright LJ, Mostoufi S, Golnari G, Reis V, et al. Psychological trauma and functional somatic syndromes: a systematic review and meta-analysis. Psychosom Med. 2014;76:2–11. [DOI] [PubMed] [PMC]

93.

Thiagarajah AS, Guymer EK, Leech M, Littlejohn GO. The relationship between fibromyalgia, stress and depression. Int J Clin Rheumtol. 2014;9:371–84. [DOI]

94.

Al-Nimer MS, Mohammad TA, Maroof AM. Dysfunction of anterior pituitary gland in women patients with recent fibromyalgia: A cross-sectional observational study. Electron J Gen Med. 2018;15:em58. [DOI]

95.

Herane-Vives A, de Angel V, Papadopoulos A, Wise T, Chua KC, Strawbridge R, et al. Short-term and long-term measures of cortisol in saliva and hair in atypical and non-atypical depression. Acta Psychiatr Scand. 2018;137:216–30. [DOI] [PubMed]

96.

Gasparini CF, Smith RA, Griffiths LR. Genetic and biochemical changes of the serotonergic system in migraine pathobiology. J Headache Pain. 2017;18:20. [DOI] [PubMed] [PMC]

97.

Bardin L. The complex role of serotonin and 5-HT receptors in chronic pain. Behav Pharmacol. 2011;22:390–404. [DOI] [PubMed]

98.

Carneiro IBC, Toscano AE, Lacerda DC, da Cunha MSB, de Castro RM, Deiró TCBJ, et al. L-tryptophan administration and increase in cerebral serotonin levels: Systematic review. Eur J Pharmacol. 2018;836:129–35. [DOI] [PubMed]

99.

Jovanovic F, Jovanovic V, Knezevic NN. Glucocorticoid Hormones as Modulators of the Kynurenine Pathway in Chronic Pain Conditions. Cells. 2023;12:1178. [DOI] [PubMed] [PMC]

100.

Tanaka M, Tóth F, Polyák H, Szabó Á, Mándi Y, Vécsei L. Immune Influencers in Action: Metabolites and Enzymes of the Tryptophan-Kynurenine Metabolic Pathway. Biomedicines. 2021;9:734. [DOI] [PubMed] [PMC]

101.

Qin Y, Wang N, Zhang X, Han X, Zhai X, Lu Y. IDO and TDO as a potential therapeutic target in different types of depression. Metab Brain Dis. 2018;33:1787–800. [DOI] [PubMed]

102.

Zhao J, Chen J, Wang C, Liu Y, Li M, Li Y, et al. Kynurenine-3-monooxygenase (KMO) broadly inhibits viral infections via triggering NMDAR/Ca²⁺ influx and CaMKII/ IRF3-mediated IFN-β production. PLoS Pathog. 2022;18:e1010366. [DOI] [PubMed] [PMC]

103.

Nematollahi A, Sun G, Jayawickrama GS, Church WB. Kynurenine Aminotransferase Isozyme Inhibitors: A Review. Int J Mol Sci. 2016;17:946. [DOI] [PubMed] [PMC]

104.

Carlin JM, Borden EC, Sondel PM, Byrne GI. Biologic-response-modifier-induced indoleamine 2,3-dioxygenase activity in human peripheral blood mononuclear cell cultures. J Immunol. 1987;139:2414–8. [PubMed]

105.

Salter M, Pogson CI. The role of tryptophan 2,3-dioxygenase in the hormonal control of tryptophan metabolism in isolated rat liver cells. Effects of glucocorticoids and experimental diabetes. Biochem J. 1985;229:499–504. [DOI] [PubMed] [PMC]

106.

Kim YK, Jeon SW. Neuroinflammation and the Immune-Kynurenine Pathway in Anxiety Disorders. Curr Neuropharmacol. 2018;16:574–82. [DOI] [PubMed] [PMC]

107.

Oxenkrug G. Serotonin – Kynurenine hypothesis of depression: historical overview and recent developments. Curr Drug Targets. 2013;14:514–21. [DOI] [PubMed] [PMC]

108.

Marx W, McGuinness AJ, Rocks T, Ruusunen A, Cleminson J, Walker AJ, et al. The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a meta-analysis of 101 studies. Mol Psychiatry. 2021;26:4158–78. [DOI] [PubMed]

109.

Auyeung A, Wang HC, Aravagiri K, Knezevic NN. Kynurenine Pathway Metabolites as Potential Biomarkers in Chronic Pain. Pharmaceuticals (Basel). 2023;16:681. [DOI] [PubMed] [PMC]

110.

Tappe-Theodor A, Kuner R. A common ground for pain and depression. Nat Neurosci. 2019;22:1612–4. [DOI] [PubMed]

111.

Athnaiel O, Ong C, Knezevic NN. The Role of Kynurenine and Its Metabolites in Comorbid Chronic Pain and Depression. Metabolites. 2022;12:950. [DOI] [PubMed] [PMC]

112.

Perkins MN, Stone TW. An iontophoretic investigation of the actions of convulsant kynurenines and their interaction with the endogenous excitant quinolinic acid. Brain Res. 1982;247:184–7. [DOI] [PubMed]

113.

Prescott C, Weeks AM, Staley KJ, Partin KM. Kynurenic acid has a dual action on AMPA receptor responses. Neurosci Lett. 2006;402:108–12. [DOI] [PubMed]

114.

Subramanian S, Haroutounian S, Palanca BJA, Lenze EJ. Ketamine as a therapeutic agent for depression and pain: mechanisms and evidence. J Neurol Sci. 2022;434:120152. [DOI] [PubMed]

115.

Rózsa E, Robotka H, Vécsei L, Toldi J. The Janus-face kynurenic acid. J Neural Transm (Vienna). 2008;115:1087–91. [DOI] [PubMed]

116.

Xiao X, Ding M, Zhang YQ. Role of the Anterior Cingulate Cortex in Translational Pain Research. Neurosci Bull. 2021;37:405–22. [DOI] [PubMed] [PMC]

117.

Kelley JM, Hughes LB, Bridges SL Jr. Does gamma-aminobutyric acid (GABA) influence the development of chronic inflammation in rheumatoid arthritis? J Neuroinflammation. 2008;5:1. [DOI] [PubMed] [PMC]

118.

Duman RS, Sanacora G, Krystal JH. Altered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficits and Reversal by Novel Treatments. Neuron. 2019;102:75–90. [DOI] [PubMed] [PMC]

119.

Hu P, Lu Y, Pan BX, Zhang WH. New Insights into the Pivotal Role of the Amygdala in Inflammation-Related Depression and Anxiety Disorder. Int J Mol Sci. 2022;23:11076. [DOI] [PubMed] [PMC]

120.

Hatziagelaki E, Tsiavou A, Gerasimou C, Vavougios GD, Spathis A, Laskos E, et al. Effects of olanzapine on cytokine profile and brain-derived neurotrophic factor in drug-naive subjects with first-episode psychosis. Exp Ther Med. 2019;17:3071–6. [DOI] [PubMed] [PMC]