Identifying Key Genes and Approved Medications Associated with Major Depressive Disorder Using Network Analysis and Systems Biology
-
Yasin Parvizi
,
Seyed Mahdi Sadati
,
Pedram Porbaha
,
Shima Masumi
,
Saeid Mahdian
,
Seyed Alireza Vafaei
,
Saeid Afshar
Abstract
Objective: Major depressive disorder (MDD) stands as one of the serious psychiatric conditions that detrimentally affect patients' quality of life and leads to a significant part of disability worldwide. Due to the limited understanding of the basic molecular mechanisms of depression and antidepressant medications, a clear understanding of the onset and development of MDD is unavailable. This study aims to figure out the pivotal genes and pathways implicated in the MDD development and identify medications that can potentially improve MDD treatment based on their relation with the key genes.
Method: Symbols of human coding genes were retrieved from the HUGO Gene Nomenclature Committee database. These symbols were then queried for MDD-related associations using a Python script in PubMed. Subsequently, genes with two or more related articles to MDD were selected. A union of our search data and MDD-related genes in the DisGeNET database was found. The gene interaction network was generated and analyzed utilizing the STRING and Cytoscape, respectively. Finally, a drug-gene network was constructed and medications that can affect multiple genes were selected.
Results: The union of our search data and DisGeNET data contained 1734 genes. Based on network analysis, TNF, IL1B, IL6, STAT1, and STAT3 were identified as the key genes in the MDD pathogenesis. Eleven drugs that affect more than one gene were detected through a drug-gene network. These medications include Acitretin, Adalimumab, Alteplase, Cisplatin, Digoxin, Etanercept, Infliximab, Insulin, Omeprazole, Pentoxifylline, and Rabeprazole.
Conclusion: In summary, our findings identified five genes as key genes in MDD development, as well as medications related to key genes. This study provides a new vision of the pathogenesis and treatment of MDD. However, further experimental and clinical studies are necessary.
1. Thom R, Silbersweig DA, Boland RJ. Major Depressive Disorder in Medical Illness: A Review of Assessment, Prevalence, and Treatment Options. Psychosom Med. 2019;81(3):246-55.
2. Albert PR. Why is depression more prevalent in women? J Psychiatry Neurosci. 2015;40(4):219-21.
3. The Lancet Global H. Mental health matters. Lancet Glob Health. 2020;8(11):e1352.
4. Kupfer DJ. The pharmacological management of depression. Dialogues Clin Neurosci. 2005;7(3):191-205.
5. Skolnick P, Popik P, Trullas R. Glutamate-based antidepressants: 20 years on. Trends Pharmacol Sci. 2009;30(11):563-9.
6. Bartova L, Lanzenberger R, Rujescu D, Kasper S. Reply to: "The serotonin theory of depression: a systematic umbrella review of the evidence" published by Moncrieff J, Cooper RE, Stockmann T, Amendola S, Hengartner MP, Horowitz MA in Molecular Psychiatry (2022 Jul 20. doi: 10.1038/s41380-022-01661-0). Mol Psychiatry. 2023;28(8):3153-4.
7. Elias E, Zhang AY, Manners MT. Novel Pharmacological Approaches to the Treatment of Depression. Life (Basel). 2022;12(2):196.
8. Pushpakom S, Iorio F, Eyers PA, Escott KJ, Hopper S, Wells A, et al. Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov. 2019;18(1):41-58.
9. Dall'Aglio L, Lewis CM, Pain O. Delineating the Genetic Component of Gene Expression in Major Depression. Biol Psychiatry. 2021;89(6):627-36.
10. Haroon E, Daguanno AW, Woolwine BJ, Goldsmith DR, Baer WM, Wommack EC, et al. Antidepressant treatment resistance is associated with increased inflammatory markers in patients with major depressive disorder. Psychoneuroendocrinology. 2018;95:43-9.
11. Zhou TT, Sun JJ, Tang LD, Yuan Y, Wang JY, Zhang L. Potential diagnostic markers and therapeutic targets for rheumatoid arthritis with comorbid depression based on bioinformatics analysis. Front Immunol. 2023;14:1007624.
12. Seal RL, Braschi B, Gray K, Jones TEM, Tweedie S, Haim-Vilmovsky L, et al. Genenames.org: the HGNC resources in 2023. Nucleic Acids Res. 2023;51(D1):D1003-d9.
13. Sethi JK, Hotamisligil GS. Metabolic Messengers: tumour necrosis factor. Nat Metab. 2021;3(10):1302-12.
14. Wang Y, Liu J, Wang Y. Role of TNF-α-induced m6A RNA methylation in diseases: a comprehensive review. Front Cell Dev Biol. 2023;11:1166308.
15. Bimpis A, Papalois A, Voumvourakis K, Oláh O, Tiszlavicz L, Liapi C. Neuronal tumour necrosis factor-α and interleukin-1β expression in a porcine model of intracerebral haemorrhage: Modulation by U-74389G. Brain Res. 2015;1615:98-105.
16. Ewen T, Qiuting L, Chaogang T, Tao T, Jun W, Liming T, et al. Neuroprotective effect of atorvastatin involves suppression of TNF-α and upregulation of IL-10 in a rat model of intracerebral hemorrhage. Cell Biochem Biophys. 2013;66(2):337-46.
17. Fasick V, Spengler RN, Samankan S, Nader ND, Ignatowski TA. The hippocampus and TNF: Common links between chronic pain and depression. Neurosci Biobehav Rev. 2015;53:139-59. Anderson G. Editorial: The Kynurenine and Melatonergic Pathways in Psychiatric and CNS Disorders. Curr Pharm Des. 2016;22(8):947-8.
19. Choi KW, Jang EH, Kim AY, Kim H, Park MJ, Byun S, et al. Predictive inflammatory biomarkers for change in suicidal ideation in major depressive disorder and panic disorder: A 12-week follow-up study. J Psychiatr Res. 2021;133:73-81.
20. Elhaik E, Zandi P. Dysregulation of the NF-κB pathway as a potential inducer of bipolar disorder. J Psychiatr Res. 2015;70:18-27.
21. Kappelmann N, Lewis G, Dantzer R, Jones PB, Khandaker GM. Antidepressant activity of anti-cytokine treatment: a systematic review and meta-analysis of clinical trials of chronic inflammatory conditions. Mol Psychiatry. 2018;23(2):335-43.
22. Köhler CA, Freitas TH, Maes M, de Andrade NQ, Liu CS, Fernandes BS, et al. Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies. Acta Psychiatr Scand. 2017;135(5):373-87.
23. Kopschina Feltes P, Doorduin J, Klein HC, Juárez-Orozco LE, Dierckx RA, Moriguchi-Jeckel CM, et al. Anti-inflammatory treatment for major depressive disorder: implications for patients with an elevated immune profile and non-responders to standard antidepressant therapy. J Psychopharmacol. 2017;31(9):1149-65.
24. Liu Y, Ho RC, Mak A. Interleukin (IL)-6, tumour necrosis factor alpha (TNF-α) and soluble interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive disorder: a meta-analysis and meta-regression. J Affect Disord. 2012;139(3):230-9.
25. Maes M, Bosmans E, Suy E, Vandervorst C, De Jonckheere C, Raus J. Immune disturbances during major depression: upregulated expression of interleukin-2 receptors. Neuropsychobiology. 1990;24(3):115-20.
26. Krishnadas R, Nicol A, Sassarini J, Puri N, Burden AD, Leman J, et al. Circulating tumour necrosis factor is highly correlated with brainstem serotonin transporter availability in humans. Brain Behav Immun. 2016;51:29-38.
27. Bradley JR. TNF-mediated inflammatory disease. J Pathol. 2008;214(2):149-60.
28. Yao L, Pan L, Qian M, Sun W, Gu C, Chen L, et al. Tumor Necrosis Factor-α Variations in Patients With Major Depressive Disorder Before and After Antidepressant Treatment. Front Psychiatry. 2020;11:518837.
29. Bayramgürler D, Karson A, Ozer C, Utkan T. Effects of long-term etanercept treatment on anxiety- and depression-like neurobehaviors in rats. Physiol Behav. 2013;119:145-8.
30. Polimeni G, Cutroneo P, Gallo A, Gallo S, Spina E, Caputi AP. Rabeprazole and psychiatric symptoms. Ann Pharmacother. 2007;41(7):1315-7.
31. Marques LJ, Zheng L, Poulakis N, Guzman J, Costabel U. Pentoxifylline inhibits TNF-alpha production from human alveolar macrophages. Am J Respir Crit Care Med. 1999;159(2):508-11.
32. El-Haggar SM, Eissa MA, Mostafa TM, El-Attar KS, Abdallah MS. The Phosphodiesterase Inhibitor Pentoxifylline as a Novel Adjunct to Antidepressants in Major Depressive Disorder Patients: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial. Psychother Psychosom. 2018;87(6):331-9.
33. Yasrebi SO, Momtazmanesh S, Moghaddam HS, Shahmansouri N, Mehrpooya M, Arbabi M, et al. Pentoxifylline for treatment of major depression after percutaneous coronary intervention or coronary artery bypass grafting: A randomized, double-blind, placebo-controlled trial. J Psychosom Res. 2021;150:110635.
34. Wang J, Fang X, Wang D, Xiao Y. Effect of intravenous thrombolysis with alteplase on clinical efficacy, inflammatory factors, and neurological function in patients with acute cerebral infarction. Braz J Med Biol Res. 2021;54(5):e10000.
35. Bavaresco DV, Uggioni MLR, Ferraz SD, Marques RMM, Simon CS, Dagostin VS, et al. Efficacy of infliximab in treatment-resistant depression: A systematic review and meta-analysis. Pharmacol Biochem Behav. 2020;188:172838.
36. Lee J, Baek S, Lee J, Lee J, Lee DG, Park MK, et al. Digoxin ameliorates autoimmune arthritis via suppression of Th17 differentiation. Int Immunopharmacol. 2015;26(1):103-11.
37. Hiromoto S, Kawashiri T, Yamanaka N, Kobayashi D, Mine K, Inoue M, et al. Use of omeprazole, the proton pump inhibitor, as a potential therapy for the capecitabine-induced hand-foot syndrome. Sci Rep. 2021;11(1):8964.
38. Abdelkader NF, Saad MA, Abdelsalam RM. Neuroprotective effect of nebivolol against cisplatin-associated depressive-like behavior in rats. J Neurochem. 2017;141(3):449-60.
39. Yaseen MM, Abuharfeil NM, Darmani H. The role of IL-1β during human immunodeficiency virus type 1 infection. Rev Med Virol. 2023;33(1):e2400.
40. Sims JE, Smith DE. The IL-1 family: regulators of immunity. Nat Rev Immunol. 2010;10(2):89-102.
41. Mikhalitskaya EV, Vyalova NM, Ermakov EA, Levchuk LA, Simutkin GG, Bokhan NA, et al. Association of Single Nucleotide Polymorphisms of Cytokine Genes with Depression, Schizophrenia and Bipolar Disorder. Genes (Basel). 2023;14(7):1470.
42. Connor TJ, Leonard BE. Depression, stress and immunological activation: the role of cytokines in depressive disorders. Life Sci. 1998;62(7):583-606.
43. Castanon N, Bluthé RM, Dantzer R. Chronic treatment with the atypical antidepressant tianeptine attenuates sickness behavior induced by peripheral but not central lipopolysaccharide and interleukin-1beta in the rat. Psychopharmacology (Berl). 2001;154(1):50-60.
44. Yu YW, Chen TJ, Hong CJ, Chen HM, Tsai SJ. Association study of the interleukin-1 beta (C-511T) genetic polymorphism with major depressive disorder, associated symptomatology, and antidepressant response. Neuropsychopharmacology. 2003;28(6):1182-5.
45. Tang M, Liu T, Jiang P, Dang R. The interaction between autophagy and neuroinflammation in major depressive disorder: From pathophysiology to therapeutic implications. Pharmacol Res. 2021;168:105586.
46. Chanchal SK, Mahajan UB, Siddharth S, Reddy N, Goyal SN, Patil PH, et al. In vivo and in vitro protective effects of omeprazole against neuropathic pain. Sci Rep. 2016;6:30007.
47. Xie J, Fan L, Xiong L, Chen P, Wang H, Chen H, et al. Rabeprazole inhibits inflammatory reaction by inhibition of cell pyroptosis in gastric epithelial cells. BMC Pharmacol Toxicol. 2021;22(1):44.
48. Elzayat EM, Shahien SA, El-Sherif AA, Hosney M. Therapeutic potential of stem cells and acitretin on inflammatory signaling pathway-associated genes regulated by miRNAs 146a and 155 in AD-like rats. Sci Rep. 2023;13(1):9613.
49. Tekin B, Salman A, Ergun T. Hidradenitis suppurativa unresponsive to canakinumab treatment: A case report. Indian J Dermatol Venereol Leprol. 2017;83(5):615-7.
50. D'Hellencourt CL, Diaw L, Cornillet P, Guenounou M. Differential regulation of TNF alpha, IL-1 beta, IL-6, IL-8, TNF beta, and IL-10 by pentoxifylline. Int J Immunopharmacol. 1996;18(12):739-48.
51. Königsberg A, Sehner S, Arlt S, Cheng B, Simonsen CZ, Boutitie F, et al. Effect of intravenous alteplase on post-stroke depression in the WAKE UP trial. Eur J Neurol. 2021;28(6):2017-25.
52. Tanaka T, Narazaki M, Ogata A, Kishimoto T. A new era for the treatment of inflammatory autoimmune diseases by interleukin-6 blockade strategy. Semin Immunol. 2014;26(1):88-96.
53. Ting EY-C, Yang AC, Tsai S-J. Role of Interleukin-6 in Depressive Disorder. International Journal of Molecular Sciences. 2020;21(6):2194.
54. Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, et al. A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010;67(5):446-57.
55. Howren MB, Lamkin DM, Suls J. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med. 2009;71(2):171-86.
56. Liu Y, Ho RC, Mak A. Interleukin (IL)-6, tumour necrosis factor alpha (TNF-α) and soluble interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive disorder: a meta-analysis and meta-regression. J Affect Disord. 2012;139(3):230-9.
57. Virtanen M, Shipley MJ, Batty GD, Hamer M, Allan CL, Lowe GD, et al. Interleukin-6 as a predictor of symptom resolution in psychological distress: a cohort study. Psychol Med. 2015;45(10):2137-44.
58. García-Juárez M, Camacho-Morales A. Defining the Role of Anti- and Pro-inflammatory Outcomes of Interleukin-6 in Mental Health. Neuroscience. 2022;492:32-46.
59. Maes M, Anderson G, Kubera M, Berk M. Targeting classical IL-6 signalling or IL-6 trans-signalling in depression? Expert Opin Ther Targets. 2014;18(5):495-512.
60. Roohi E, Jaafari N, Hashemian F. On inflammatory hypothesis of depression: what is the role of IL-6 in the middle of the chaos? J Neuroinflammation. 2021;18(1):45.
61. Faubel S, Lewis EC, Reznikov L, Ljubanovic D, Hoke TS, Somerset H, et al. Cisplatin-induced acute renal failure is associated with an increase in the cytokines interleukin (IL)-1beta, IL-18, IL-6, and neutrophil infiltration in the kidney. J Pharmacol Exp Ther. 2007;322(1):8-15.
62. Musacchio E, Valvason C, Botsios C, Ostuni F, Furlan A, Ramonda R, et al. The tumor necrosis factor-{alpha}-blocking agent infliximab inhibits interleukin 1beta (IL-1beta) and IL-6 gene expression in human osteoblastic cells. J Rheumatol. 2009;36(8):1575-9.
63. Yue C, You X, Zhao L, Wang H, Tang F, Zhang F, et al. The effects of adalimumab and methotrexate treatment on peripheral Th17 cells and IL-17/IL-6 secretion in rheumatoid arthritis patients. Rheumatol Int. 2010;30(12):1553-7.
64. Li S, Mei Q, Qian D, Huang X, Fan C, Quan J. Efficacy of etanercept in rheumatoid arthritis patients and its effects on interleukin 6 and serum tumor necrosis factor α. Trop J Pharm Res. 2023;22(1):207-13.
65. Fasshauer M, Klein J, Lossner U, Paschke R. Interleukin (IL)-6 mRNA expression is stimulated by insulin, isoproterenol, tumour necrosis factor alpha, growth hormone, and IL-6 in 3T3-L1 adipocytes. Horm Metab Res. 2003;35(3):147-52.
66. Guanizo AC, Fernando CD, Garama DJ, Gough DJ. STAT3: a multifaceted oncoprotein. Growth Factors. 2018;36(1-2):1-14.
67. Kong E, Sucic S, Monje FJ, Savalli G, Diao W, Khan D, et al. STAT3 controls IL6-dependent regulation of serotonin transporter function and depression-like behavior. Sci Rep. 2015;5:9009.
68. Kwon SH, Han JK, Choi M, Kwon YJ, Kim SJ, Yi EH, et al. Dysfunction of Microglial STAT3 Alleviates Depressive Behavior via Neuron-Microglia Interactions. Neuropsychopharmacology. 2017;42(10):2072-86.
69. Wong ML, Dong C, Maestre-Mesa J, Licinio J. Polymorphisms in inflammation-related genes are associated with susceptibility to major depression and antidepressant response. Mol Psychiatry. 2008;13(8):800-12.
70. Panda SP, Kesharwani A, Datta S, Prasanth D, Panda SK, Guru A. JAK2/STAT3 as a new potential target to manage neurodegenerative diseases: An interactive review. Eur J Pharmacol. 2024;970:176490.
71. Qin X, Chen C, Zhang Y, Zhang L, Mei Y, Long X, et al. Acitretin modulates HaCaT cells proliferation through STAT1- and STAT3-dependent signaling. Saudi Pharm J. 2017;25(4):620-4.
72. Hayes J, Koo J. Depression and acitretin: a true association or a class labeling? J Drugs Dermatol. 2011;10(4):409-12.
73. Lin SY, Chang HH, Lai YH, Lin CH, Chen MH, Chang GC, et al. Digoxin Suppresses Tumor Malignancy through Inhibiting Multiple Src-Related Signaling Pathways in Non-Small Cell Lung Cancer. PLoS One. 2015;10(5):e0123305.
74. Schleifer SJ, Slater WR, Macari-Hinson MM, Coyle DA, Kahn M, Zucker HD, et al. Digitalis and beta-blocking agents: effects on depression following myocardial infarction. Am Heart J. 1991;121(5):1397-402.
75. Keller S, Frishman WH. Neuropsychiatric effects of cardiovascular drug therapy. Cardiol Rev. 2003;11(2):73-93.
76. Gałecka M, Szemraj J, Su KP, Halaris A, Maes M, Skiba A, et al. Is the JAK-STAT Signaling Pathway Involved in the Pathogenesis of Depression? J Clin Med. 2022;11(7).
77. Sforzini L, Cattaneo A, Ferrari C, Turner L, Mariani N, Enache D, et al. Higher immune-related gene expression in major depression is independent of CRP levels: results from the BIODEP study. Transl Psychiatry. 2023;13(1):185.
78. Schmitt NC, Trivedi S, Ferris RL. STAT1 Activation Is Enhanced by Cisplatin and Variably Affected by EGFR Inhibition in HNSCC Cells. Mol Cancer Ther. 2015;14(9):2103-11.
79. Kandeil MA, Gomaa SB, Mahmoud MO. The effect of some natural antioxidants against cisplatin-induced neurotoxicity in rats: behavioral testing. Heliyon. 2020;6(8):e04708.
80. López-León S, Janssens AC, González-Zuloeta Ladd AM, Del-Favero J, Claes SJ, Oostra BA, et al. Meta-analyses of genetic studies on major depressive disorder. Mol Psychiatry. 2008;13(8):772-85.
81. Bosker FJ, Hartman CA, Nolte IM, Prins BP, Terpstra P, Posthuma D, et al. Poor replication of candidate genes for major depressive disorder using genome-wide association data. Mol Psychiatry. 2011;16(5):516-32.
82. Chang LC, Jamain S, Lin CW, Rujescu D, Tseng GC, Sibille E. A conserved BDNF, glutamate- and GABA-enriched gene module related to human depression identified by coexpression meta-analysis and DNA variant genome-wide association studies. PLoS One. 2014;9(3):e90980.
83. Geng HM, Chuang DM, Yang F, Yang Y, Liu WM, Liu LH, et al. Prevalence and determinants of depression in caregivers of cancer patients: A systematic review and meta-analysis. Medicine (Baltimore). 2018;97(39):e11863.
84. Walker J, Mulick A, Magill N, Symeonides S, Gourley C, Burke K, et al. Major Depression and Survival in People With Cancer. Psychosom Med. 2021;83(5):410-6.
2. Albert PR. Why is depression more prevalent in women? J Psychiatry Neurosci. 2015;40(4):219-21.
3. The Lancet Global H. Mental health matters. Lancet Glob Health. 2020;8(11):e1352.
4. Kupfer DJ. The pharmacological management of depression. Dialogues Clin Neurosci. 2005;7(3):191-205.
5. Skolnick P, Popik P, Trullas R. Glutamate-based antidepressants: 20 years on. Trends Pharmacol Sci. 2009;30(11):563-9.
6. Bartova L, Lanzenberger R, Rujescu D, Kasper S. Reply to: "The serotonin theory of depression: a systematic umbrella review of the evidence" published by Moncrieff J, Cooper RE, Stockmann T, Amendola S, Hengartner MP, Horowitz MA in Molecular Psychiatry (2022 Jul 20. doi: 10.1038/s41380-022-01661-0). Mol Psychiatry. 2023;28(8):3153-4.
7. Elias E, Zhang AY, Manners MT. Novel Pharmacological Approaches to the Treatment of Depression. Life (Basel). 2022;12(2):196.
8. Pushpakom S, Iorio F, Eyers PA, Escott KJ, Hopper S, Wells A, et al. Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov. 2019;18(1):41-58.
9. Dall'Aglio L, Lewis CM, Pain O. Delineating the Genetic Component of Gene Expression in Major Depression. Biol Psychiatry. 2021;89(6):627-36.
10. Haroon E, Daguanno AW, Woolwine BJ, Goldsmith DR, Baer WM, Wommack EC, et al. Antidepressant treatment resistance is associated with increased inflammatory markers in patients with major depressive disorder. Psychoneuroendocrinology. 2018;95:43-9.
11. Zhou TT, Sun JJ, Tang LD, Yuan Y, Wang JY, Zhang L. Potential diagnostic markers and therapeutic targets for rheumatoid arthritis with comorbid depression based on bioinformatics analysis. Front Immunol. 2023;14:1007624.
12. Seal RL, Braschi B, Gray K, Jones TEM, Tweedie S, Haim-Vilmovsky L, et al. Genenames.org: the HGNC resources in 2023. Nucleic Acids Res. 2023;51(D1):D1003-d9.
13. Sethi JK, Hotamisligil GS. Metabolic Messengers: tumour necrosis factor. Nat Metab. 2021;3(10):1302-12.
14. Wang Y, Liu J, Wang Y. Role of TNF-α-induced m6A RNA methylation in diseases: a comprehensive review. Front Cell Dev Biol. 2023;11:1166308.
15. Bimpis A, Papalois A, Voumvourakis K, Oláh O, Tiszlavicz L, Liapi C. Neuronal tumour necrosis factor-α and interleukin-1β expression in a porcine model of intracerebral haemorrhage: Modulation by U-74389G. Brain Res. 2015;1615:98-105.
16. Ewen T, Qiuting L, Chaogang T, Tao T, Jun W, Liming T, et al. Neuroprotective effect of atorvastatin involves suppression of TNF-α and upregulation of IL-10 in a rat model of intracerebral hemorrhage. Cell Biochem Biophys. 2013;66(2):337-46.
17. Fasick V, Spengler RN, Samankan S, Nader ND, Ignatowski TA. The hippocampus and TNF: Common links between chronic pain and depression. Neurosci Biobehav Rev. 2015;53:139-59. Anderson G. Editorial: The Kynurenine and Melatonergic Pathways in Psychiatric and CNS Disorders. Curr Pharm Des. 2016;22(8):947-8.
19. Choi KW, Jang EH, Kim AY, Kim H, Park MJ, Byun S, et al. Predictive inflammatory biomarkers for change in suicidal ideation in major depressive disorder and panic disorder: A 12-week follow-up study. J Psychiatr Res. 2021;133:73-81.
20. Elhaik E, Zandi P. Dysregulation of the NF-κB pathway as a potential inducer of bipolar disorder. J Psychiatr Res. 2015;70:18-27.
21. Kappelmann N, Lewis G, Dantzer R, Jones PB, Khandaker GM. Antidepressant activity of anti-cytokine treatment: a systematic review and meta-analysis of clinical trials of chronic inflammatory conditions. Mol Psychiatry. 2018;23(2):335-43.
22. Köhler CA, Freitas TH, Maes M, de Andrade NQ, Liu CS, Fernandes BS, et al. Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies. Acta Psychiatr Scand. 2017;135(5):373-87.
23. Kopschina Feltes P, Doorduin J, Klein HC, Juárez-Orozco LE, Dierckx RA, Moriguchi-Jeckel CM, et al. Anti-inflammatory treatment for major depressive disorder: implications for patients with an elevated immune profile and non-responders to standard antidepressant therapy. J Psychopharmacol. 2017;31(9):1149-65.
24. Liu Y, Ho RC, Mak A. Interleukin (IL)-6, tumour necrosis factor alpha (TNF-α) and soluble interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive disorder: a meta-analysis and meta-regression. J Affect Disord. 2012;139(3):230-9.
25. Maes M, Bosmans E, Suy E, Vandervorst C, De Jonckheere C, Raus J. Immune disturbances during major depression: upregulated expression of interleukin-2 receptors. Neuropsychobiology. 1990;24(3):115-20.
26. Krishnadas R, Nicol A, Sassarini J, Puri N, Burden AD, Leman J, et al. Circulating tumour necrosis factor is highly correlated with brainstem serotonin transporter availability in humans. Brain Behav Immun. 2016;51:29-38.
27. Bradley JR. TNF-mediated inflammatory disease. J Pathol. 2008;214(2):149-60.
28. Yao L, Pan L, Qian M, Sun W, Gu C, Chen L, et al. Tumor Necrosis Factor-α Variations in Patients With Major Depressive Disorder Before and After Antidepressant Treatment. Front Psychiatry. 2020;11:518837.
29. Bayramgürler D, Karson A, Ozer C, Utkan T. Effects of long-term etanercept treatment on anxiety- and depression-like neurobehaviors in rats. Physiol Behav. 2013;119:145-8.
30. Polimeni G, Cutroneo P, Gallo A, Gallo S, Spina E, Caputi AP. Rabeprazole and psychiatric symptoms. Ann Pharmacother. 2007;41(7):1315-7.
31. Marques LJ, Zheng L, Poulakis N, Guzman J, Costabel U. Pentoxifylline inhibits TNF-alpha production from human alveolar macrophages. Am J Respir Crit Care Med. 1999;159(2):508-11.
32. El-Haggar SM, Eissa MA, Mostafa TM, El-Attar KS, Abdallah MS. The Phosphodiesterase Inhibitor Pentoxifylline as a Novel Adjunct to Antidepressants in Major Depressive Disorder Patients: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial. Psychother Psychosom. 2018;87(6):331-9.
33. Yasrebi SO, Momtazmanesh S, Moghaddam HS, Shahmansouri N, Mehrpooya M, Arbabi M, et al. Pentoxifylline for treatment of major depression after percutaneous coronary intervention or coronary artery bypass grafting: A randomized, double-blind, placebo-controlled trial. J Psychosom Res. 2021;150:110635.
34. Wang J, Fang X, Wang D, Xiao Y. Effect of intravenous thrombolysis with alteplase on clinical efficacy, inflammatory factors, and neurological function in patients with acute cerebral infarction. Braz J Med Biol Res. 2021;54(5):e10000.
35. Bavaresco DV, Uggioni MLR, Ferraz SD, Marques RMM, Simon CS, Dagostin VS, et al. Efficacy of infliximab in treatment-resistant depression: A systematic review and meta-analysis. Pharmacol Biochem Behav. 2020;188:172838.
36. Lee J, Baek S, Lee J, Lee J, Lee DG, Park MK, et al. Digoxin ameliorates autoimmune arthritis via suppression of Th17 differentiation. Int Immunopharmacol. 2015;26(1):103-11.
37. Hiromoto S, Kawashiri T, Yamanaka N, Kobayashi D, Mine K, Inoue M, et al. Use of omeprazole, the proton pump inhibitor, as a potential therapy for the capecitabine-induced hand-foot syndrome. Sci Rep. 2021;11(1):8964.
38. Abdelkader NF, Saad MA, Abdelsalam RM. Neuroprotective effect of nebivolol against cisplatin-associated depressive-like behavior in rats. J Neurochem. 2017;141(3):449-60.
39. Yaseen MM, Abuharfeil NM, Darmani H. The role of IL-1β during human immunodeficiency virus type 1 infection. Rev Med Virol. 2023;33(1):e2400.
40. Sims JE, Smith DE. The IL-1 family: regulators of immunity. Nat Rev Immunol. 2010;10(2):89-102.
41. Mikhalitskaya EV, Vyalova NM, Ermakov EA, Levchuk LA, Simutkin GG, Bokhan NA, et al. Association of Single Nucleotide Polymorphisms of Cytokine Genes with Depression, Schizophrenia and Bipolar Disorder. Genes (Basel). 2023;14(7):1470.
42. Connor TJ, Leonard BE. Depression, stress and immunological activation: the role of cytokines in depressive disorders. Life Sci. 1998;62(7):583-606.
43. Castanon N, Bluthé RM, Dantzer R. Chronic treatment with the atypical antidepressant tianeptine attenuates sickness behavior induced by peripheral but not central lipopolysaccharide and interleukin-1beta in the rat. Psychopharmacology (Berl). 2001;154(1):50-60.
44. Yu YW, Chen TJ, Hong CJ, Chen HM, Tsai SJ. Association study of the interleukin-1 beta (C-511T) genetic polymorphism with major depressive disorder, associated symptomatology, and antidepressant response. Neuropsychopharmacology. 2003;28(6):1182-5.
45. Tang M, Liu T, Jiang P, Dang R. The interaction between autophagy and neuroinflammation in major depressive disorder: From pathophysiology to therapeutic implications. Pharmacol Res. 2021;168:105586.
46. Chanchal SK, Mahajan UB, Siddharth S, Reddy N, Goyal SN, Patil PH, et al. In vivo and in vitro protective effects of omeprazole against neuropathic pain. Sci Rep. 2016;6:30007.
47. Xie J, Fan L, Xiong L, Chen P, Wang H, Chen H, et al. Rabeprazole inhibits inflammatory reaction by inhibition of cell pyroptosis in gastric epithelial cells. BMC Pharmacol Toxicol. 2021;22(1):44.
48. Elzayat EM, Shahien SA, El-Sherif AA, Hosney M. Therapeutic potential of stem cells and acitretin on inflammatory signaling pathway-associated genes regulated by miRNAs 146a and 155 in AD-like rats. Sci Rep. 2023;13(1):9613.
49. Tekin B, Salman A, Ergun T. Hidradenitis suppurativa unresponsive to canakinumab treatment: A case report. Indian J Dermatol Venereol Leprol. 2017;83(5):615-7.
50. D'Hellencourt CL, Diaw L, Cornillet P, Guenounou M. Differential regulation of TNF alpha, IL-1 beta, IL-6, IL-8, TNF beta, and IL-10 by pentoxifylline. Int J Immunopharmacol. 1996;18(12):739-48.
51. Königsberg A, Sehner S, Arlt S, Cheng B, Simonsen CZ, Boutitie F, et al. Effect of intravenous alteplase on post-stroke depression in the WAKE UP trial. Eur J Neurol. 2021;28(6):2017-25.
52. Tanaka T, Narazaki M, Ogata A, Kishimoto T. A new era for the treatment of inflammatory autoimmune diseases by interleukin-6 blockade strategy. Semin Immunol. 2014;26(1):88-96.
53. Ting EY-C, Yang AC, Tsai S-J. Role of Interleukin-6 in Depressive Disorder. International Journal of Molecular Sciences. 2020;21(6):2194.
54. Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, et al. A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010;67(5):446-57.
55. Howren MB, Lamkin DM, Suls J. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med. 2009;71(2):171-86.
56. Liu Y, Ho RC, Mak A. Interleukin (IL)-6, tumour necrosis factor alpha (TNF-α) and soluble interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive disorder: a meta-analysis and meta-regression. J Affect Disord. 2012;139(3):230-9.
57. Virtanen M, Shipley MJ, Batty GD, Hamer M, Allan CL, Lowe GD, et al. Interleukin-6 as a predictor of symptom resolution in psychological distress: a cohort study. Psychol Med. 2015;45(10):2137-44.
58. García-Juárez M, Camacho-Morales A. Defining the Role of Anti- and Pro-inflammatory Outcomes of Interleukin-6 in Mental Health. Neuroscience. 2022;492:32-46.
59. Maes M, Anderson G, Kubera M, Berk M. Targeting classical IL-6 signalling or IL-6 trans-signalling in depression? Expert Opin Ther Targets. 2014;18(5):495-512.
60. Roohi E, Jaafari N, Hashemian F. On inflammatory hypothesis of depression: what is the role of IL-6 in the middle of the chaos? J Neuroinflammation. 2021;18(1):45.
61. Faubel S, Lewis EC, Reznikov L, Ljubanovic D, Hoke TS, Somerset H, et al. Cisplatin-induced acute renal failure is associated with an increase in the cytokines interleukin (IL)-1beta, IL-18, IL-6, and neutrophil infiltration in the kidney. J Pharmacol Exp Ther. 2007;322(1):8-15.
62. Musacchio E, Valvason C, Botsios C, Ostuni F, Furlan A, Ramonda R, et al. The tumor necrosis factor-{alpha}-blocking agent infliximab inhibits interleukin 1beta (IL-1beta) and IL-6 gene expression in human osteoblastic cells. J Rheumatol. 2009;36(8):1575-9.
63. Yue C, You X, Zhao L, Wang H, Tang F, Zhang F, et al. The effects of adalimumab and methotrexate treatment on peripheral Th17 cells and IL-17/IL-6 secretion in rheumatoid arthritis patients. Rheumatol Int. 2010;30(12):1553-7.
64. Li S, Mei Q, Qian D, Huang X, Fan C, Quan J. Efficacy of etanercept in rheumatoid arthritis patients and its effects on interleukin 6 and serum tumor necrosis factor α. Trop J Pharm Res. 2023;22(1):207-13.
65. Fasshauer M, Klein J, Lossner U, Paschke R. Interleukin (IL)-6 mRNA expression is stimulated by insulin, isoproterenol, tumour necrosis factor alpha, growth hormone, and IL-6 in 3T3-L1 adipocytes. Horm Metab Res. 2003;35(3):147-52.
66. Guanizo AC, Fernando CD, Garama DJ, Gough DJ. STAT3: a multifaceted oncoprotein. Growth Factors. 2018;36(1-2):1-14.
67. Kong E, Sucic S, Monje FJ, Savalli G, Diao W, Khan D, et al. STAT3 controls IL6-dependent regulation of serotonin transporter function and depression-like behavior. Sci Rep. 2015;5:9009.
68. Kwon SH, Han JK, Choi M, Kwon YJ, Kim SJ, Yi EH, et al. Dysfunction of Microglial STAT3 Alleviates Depressive Behavior via Neuron-Microglia Interactions. Neuropsychopharmacology. 2017;42(10):2072-86.
69. Wong ML, Dong C, Maestre-Mesa J, Licinio J. Polymorphisms in inflammation-related genes are associated with susceptibility to major depression and antidepressant response. Mol Psychiatry. 2008;13(8):800-12.
70. Panda SP, Kesharwani A, Datta S, Prasanth D, Panda SK, Guru A. JAK2/STAT3 as a new potential target to manage neurodegenerative diseases: An interactive review. Eur J Pharmacol. 2024;970:176490.
71. Qin X, Chen C, Zhang Y, Zhang L, Mei Y, Long X, et al. Acitretin modulates HaCaT cells proliferation through STAT1- and STAT3-dependent signaling. Saudi Pharm J. 2017;25(4):620-4.
72. Hayes J, Koo J. Depression and acitretin: a true association or a class labeling? J Drugs Dermatol. 2011;10(4):409-12.
73. Lin SY, Chang HH, Lai YH, Lin CH, Chen MH, Chang GC, et al. Digoxin Suppresses Tumor Malignancy through Inhibiting Multiple Src-Related Signaling Pathways in Non-Small Cell Lung Cancer. PLoS One. 2015;10(5):e0123305.
74. Schleifer SJ, Slater WR, Macari-Hinson MM, Coyle DA, Kahn M, Zucker HD, et al. Digitalis and beta-blocking agents: effects on depression following myocardial infarction. Am Heart J. 1991;121(5):1397-402.
75. Keller S, Frishman WH. Neuropsychiatric effects of cardiovascular drug therapy. Cardiol Rev. 2003;11(2):73-93.
76. Gałecka M, Szemraj J, Su KP, Halaris A, Maes M, Skiba A, et al. Is the JAK-STAT Signaling Pathway Involved in the Pathogenesis of Depression? J Clin Med. 2022;11(7).
77. Sforzini L, Cattaneo A, Ferrari C, Turner L, Mariani N, Enache D, et al. Higher immune-related gene expression in major depression is independent of CRP levels: results from the BIODEP study. Transl Psychiatry. 2023;13(1):185.
78. Schmitt NC, Trivedi S, Ferris RL. STAT1 Activation Is Enhanced by Cisplatin and Variably Affected by EGFR Inhibition in HNSCC Cells. Mol Cancer Ther. 2015;14(9):2103-11.
79. Kandeil MA, Gomaa SB, Mahmoud MO. The effect of some natural antioxidants against cisplatin-induced neurotoxicity in rats: behavioral testing. Heliyon. 2020;6(8):e04708.
80. López-León S, Janssens AC, González-Zuloeta Ladd AM, Del-Favero J, Claes SJ, Oostra BA, et al. Meta-analyses of genetic studies on major depressive disorder. Mol Psychiatry. 2008;13(8):772-85.
81. Bosker FJ, Hartman CA, Nolte IM, Prins BP, Terpstra P, Posthuma D, et al. Poor replication of candidate genes for major depressive disorder using genome-wide association data. Mol Psychiatry. 2011;16(5):516-32.
82. Chang LC, Jamain S, Lin CW, Rujescu D, Tseng GC, Sibille E. A conserved BDNF, glutamate- and GABA-enriched gene module related to human depression identified by coexpression meta-analysis and DNA variant genome-wide association studies. PLoS One. 2014;9(3):e90980.
83. Geng HM, Chuang DM, Yang F, Yang Y, Liu WM, Liu LH, et al. Prevalence and determinants of depression in caregivers of cancer patients: A systematic review and meta-analysis. Medicine (Baltimore). 2018;97(39):e11863.
84. Walker J, Mulick A, Magill N, Symeonides S, Gourley C, Burke K, et al. Major Depression and Survival in People With Cancer. Psychosom Med. 2021;83(5):410-6.
| Files | ||
| Issue | Vol 19 No 4 (2024) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijps.v19i4.16550 | |
| Keywords | ||
| Antidepressive Agents Depressive Disorder Drug Therapy Major Protein Interaction Maps Systems Biology | ||
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How to Cite
1.
Parvizi Y, Sadati SM, Porbaha P, Masumi S, Mahdian S, Vafaei SA, Afshar S. Identifying Key Genes and Approved Medications Associated with Major Depressive Disorder Using Network Analysis and Systems Biology. Iran J Psychiatry. 2024;19(4):367-383.
