Research Article
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Antidepresan tedavi başlanan major depresyon hastalarında inflamatuar parametrelerdeki değişikliklerin tedavi yanıtı ile ilişkisi

Year 2021, Volume: 5 Issue: 2, 118 - 125, 30.08.2021
https://doi.org/10.30565/medalanya.880254

Abstract

Amaç: Depresyonda meydana gelen sitokinler, stres hormonları ve C reaktif protein gibi inflamatuvar parametrelerin değişimi, depresyonun patofizyolojisinin anlaşılması ve yeni tedavi yaklaşımlarının geliştirilmesi açısından önem taşımaktadır. Bu çalışmanın temel amacı, major depresyon hastalarında antidepresan tedavi öncesi ve sonrasında inflamatuvar belirteçlerde nasıl bir değişiklik olduğunu tespit etmek ve antidepresan tedavi türünün bu değişiklikler üzerindeki etkisini belirlemektir.

Yöntem: Tek merkezli, retrospektif olarak gerçekleştirilen çalışmada, Alanya Alaaddin Keykubat Üniversitesi Eğitim ve Araştırma Hastanesi psikiyatri polikliniğinde son beş yıla ait geriye dönük incelenen kayıtlara göre, Majör Depresif Bozukluk (MDB) tanısı konulup, ilk kez tekli antidepresan tedavisine başlanan ve en az 6-8 hafta antidepresan tedavi kullanmış, tedavi öncesi ve sonrası Hamilton Depresyon Derecelendirme Ölçeği (HDDÖ), tam kan sayımı, C reaktif protein, kortizol değerlerine ulaşılabilen hastalar çalışmanın örneklemini oluşturmuştur.

Bulgular: Çalışmamızda, antidepresan tedavi sonrası, HDDÖ puanları Majör Depresyonlu hastalarda tedavi öncesine göre anlamlı olarak azalırken (p<0,001), inflamatuar parametrelerdeki değişiklikler ile tedaviye yanıt arasında anlamlı bir ilişki belirlenmemiştir (p>0,05). Bu durum, tedavide kullanılan antidepresan ilaç türünden bağımsızdır (SSRI tedavi grubunda p>0,05, SNRI tedavi grubunda p>0,05). Ayrıca depresyon puanlarındaki azalmanın da, antidepresan ilaç türü (SSRI-SNRI) ile ilişkili olmadığı belirlenmiştir (SSRI tedavi grubunda, p=0,001, SNRI tedavi grubunda, p=0,005).

Sonuç: Çalışmamızda, MDB’de inflamatuar hipotezi destekleyecek sonuçlar belirlenmemiştir. Depresyonun patofizyolojisinin oldukça karmaşık olduğu düşünüldüğünde, inflamasyon ve depresyon arasındaki bağlantıyı açıklamak için yalnızca bir grup kan testinin yeterli olmayabileceği düşünülebilir. Çalışmamızdaki tüm sınırlılıklar göz önünde bulundurulduğunda, gelecekte daha kapsamlı kan, BOS testleri ile beraber beyin yolaklarına ilişkin nörogörüntüleme parametrelerini de içeren prospektif çalışmalar, MDB’de inflamatuar hipotezi kanıtlamak için daha etkili sonuçlar sağlayabilir. 


References

  • 1. Guilbert J. The world health report 2002–reducing risks, promoting healthy life. Educ Health. 2003;16:230. PMID: 14741909.
  • 2. Bierhaus A, Wolf J, Andrassy M, Rohleder N, Humpert PM, Petrov D, et al. A mechanism converting psychosocial stress into mononuclear cell activation. Proc Natl Acad Sci USA. 2003;100:1920-5. PMID: 12578963.
  • 3. Aschbacher K, Epel E, Wolkowitz O, Prather A, Puterman E, Dhabhar F. Maintenance of a positive outlook during acute stress protects against pro-inflammatory reactivity and future depressive symptoms. Brain Behav Immun. 2012;26:346-52. PMID: 22119400.
  • 4. Krishnan V, Nestler EJ. The molecular neurobiology of depression. Nature. 2008; 455:894-902. PMID: 18923511.
  • 5. 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. PMID: 29604382.
  • 6. Carvalho L, Torre J, Papadopoulos A, Poon L, Juruena M, Markopoulou K, et al. Lack of clinical therapeutic benefit of antidepressants is associated overall activation of the inflammatory system. J Affect Disorder. 2013;148:136-40. PMID: 23200297.
  • 7. Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry. 2009;65:732-41. PMID: 19150053.
  • 8. Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006;27:24-31. PMID: 16316783.
  • 9. Yulug B. Neuroprotective treatment strategies for poststroke mood disorders: A minireview on atypical neuroleptic drugs and selective serotonin re-uptake inhibitors. Brain Res Bull. 2009;80:95-9. PMID: 19576272.
  • 10. Yuluğ B, Ozan E, Kilic E. Brain-derived neurotrophic factor polymorphism as a genetic risk for depression? A short review of the literature. J Neuropsychiatry Clin Neurosci. 2010;22:123. E5-6. PMID: 20160224.
  • 11. Lapchak PA, Zhang JH. Neuroprotective therapy for stroke and ischemic disease. Switzerland: Springer International Publishing, 2017. p. 607-20. doi:10.1007/978-3-319-45345-3.
  • 12. Cai L, Xu L, Wei L, Chen W. Relationship of mean platelet volume to MDD: a retrospective study. Shanghai Arch Psychiatry. 2017;29:21-9. PMID: 28769542.
  • 13. Kasama T, Miwa Y, Isozaki T, Odai T, Adachi M, Kunkel SL. Neutrophil-derived cytokines: potential therapeutic targets in inflammation. Curr Drug Targets Inflamm Allergy. 2005;4:273-9. PMID: 16101533.
  • 14. Amodeo G, Trusso MA, Fagiolini A. Depression and inflammation: disentangling a clear yet complex and multifaceted link. Neuropsychiatry. 2017;7:448-57. doi: 10.4172/Neuropsychiatry.1000236
  • 15. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56-62. PMID: 14399272.
  • 16. Akdemir A, Türkçapar M, Örsel S, Demirergi N, Dag I, Özbay M. Reliability and validity of the Turkish version of the Hamilton Depression Rating Scale. Compr Psychiatry. 2001;42:161-5. PMID: 11244153.
  • 17. SPSS I: IBM SPSS statistics for windows. Armonk, New York, USA: IBM SPSS 2013.
  • 18. Liu Y, Ho RC-M, 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 Disorder. 2012;139:230-9. PMID: 21872339.
  • 19. Gimeno D, Kivimäki M, Brunner EJ, Elovainio M, De Vogli R, Steptoe A, et al. Associations of C-reactive protein and interleukin-6 with cognitive symptoms of depression: 12-year follow-up of the Whitehall II study. Psychol Med. 2009;39:413-23. PMID: 18533059.
  • 20. Demircan F, Gözel N, Kılınç F, Ulu R, Atmaca M. The impact of red blood cell distribution width and neutrophil/lymphocyte ratio on the diagnosis of major depressive disorder. Neurol Ther. 2016;5:27-33. PMID: 26686339.
  • 21. Osimo EF, Baxter LJ, Lewis G, Jones PB, Khandaker GM. Prevalence of low-grade inflammation in depression: a systematic review and meta-analysis of CRP levels. Psychol Med. 2019;49:1958-70. PMID: 31258105.
  • 22. Dooley LN, Kuhlman KR, Robles TF, Eisenberger NI, Craske MG, Bower JE. The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. Neurosci Biobehav Rev. 2018;94:219-37. PMID: 30201219.
  • 23. Howren MB, Lamkin DM, Suls J. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med. 2009;71:171-86. PMID: 19188531.
  • 24. Fried EI, Von Stockert S, Haslbeck J, Lamers F, Schoevers R, Penninx B. Using network analysis to examine links between individual depressive symptoms, inflammatory markers, and covariates. Psychol Med. 2020;50:2682-90. PMID: 31615595.
  • 25. Maes M, Van de Vyvere J, Vandoolaeghe E, Bril T, Demedts P, Wauters A, et al. Alterations in iron metabolism and the erythron in major depression: further evidence for a chronic inflammatory process. J Affect Disorder. 1996;40:23-33. PMID: 8882911.
  • 26. Raison CL, Rutherford RE, Woolwine BJ, Shuo C, Schettler P, Drake DF, et al. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry 2013;70:31-41. PMID: 22945416.
  • 27. Uher R, Tansey KE, Dew T, Maier W, Mors O, Hauser J, et al. An inflammatory biomarker as a differential predictor of outcome of depression treatment with escitalopram and nortriptyline. Am J Psychiatry. 2014;171:1278-86. PMID: 25017001.
  • 28. Meng G, Wang L, Wang X, Chi VTQ, Zhang Q, Liu L, et al. Association between neutrophil to lymphocyte ratio and depressive symptoms among Chinese adults: a population study from the TCLSIH cohort study. Psychoneuroendocrinology. 2019;103:76-82. PMID: 30658341.
  • 29. Islam MR, Islam MR, Ahmed I, Moktadir AA, Nahar Z, Islam MS, et al. Elevated serum levels of malondialdehyde and cortisol are associated with major depressive disorder: a case-control study. SAGE Open Med. 2018;6:2050312118773953. PMID: 29770218.
  • 30. Alenko A, Markos Y, Fikru C, Tadesse E, Gedefaw L. Association of serum cortisol level with severity of depression and improvement in newly diagnosed patients with major depressive disorder in Jimma medical center, Southwest Ethiopia. Plos One. 2020;15:e0240668. PMID: 33064754.
  • 31. Haroon E, Woolwine BJ, Chen X, Pace TW, Parekh S, Spivey JR, et al. IFN-alpha-induced cortical and subcortical glutamate changes assessed by magnetic resonance spectroscopy. Neuropsychopharmacology. 2014;39:1777-85. PMID: 24481242.
  • 32. Miller AH, Raison CL. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol. 2016;16:22-34. PMID: 26711676.
  • 33. Shafiee M, Tayefi M, Hassanian SM, Ghaneifar Z, Parizadeh MR, Avan A, et al. Depression and anxiety symptoms are associated with white blood cell count and red cell distribution width: a sex-stratified analysis in a population-based study. Psychoneuroendocrinology. 2017;84:101-8. PMID: 28697416.

The relationship between the changes in inflammatory parameters and response to treatment in major depression patients starting antidepressant treatment

Year 2021, Volume: 5 Issue: 2, 118 - 125, 30.08.2021
https://doi.org/10.30565/medalanya.880254

Abstract

Aim: Changes in inflammatory parameters such as cytokines, stress hormones and C reactive protein that occur in depression, are important in understanding the pathophysiology of depression and developing new treatment approaches. The main purpose of this study was to determine the changes in inflammatory markers in patients with major depression, before and after antidepressant treatment, as well as to determine the effect of antidepressant treatment types on these changes.

Methods: This study was a single center, retrospective study. According to the retrospective records of the last five years in the psychiatry outpatient clinic of Alanya Alaaddin Keykubat University Training and Research Hospital, the patients diagnosed with Major Depressive Disorder (MDD), started on single antidepressant treatment for the first time and who used antidepressant treatment for at least 6-8 weeks, were included in the study. Patients whose Hamilton Depression Rating Scale (HDRS), complete blood count, C reactive protein and cortisol values were reached from the system during MDD treatment, constituted the sample of the study.

Results: In the present study, after the antidepressant treatment, while HDRS scores decreased significantly in patients with Major Depression compared to before treatment (p<0,001), no significant correlation was found between the changes in inflammatory parameters and the response to treatment (p>0,05). This condition was independent of the type of antidepressant used in the treatment (p>0,05 in the SSRI treatment group, p>0,05 in the SNRI treatment group). In addition, it was observed that the decrease in depression scores was not associated with the type of antidepressant (p=0,001, in the SSRI treatment group, p=0,005, in the SNRI treatment group).

Conclusion: Results to support the inflammatory hypothesis in Major Depressive Disorder were not conclusive in this study. Considering that the pathophysiology of depression is quite complex, it could be argued that a single group of blood tests may not be sufficient to explain the link between inflammation and depression. Considering all the limitations of the study, a future a prospective study to prove the inflammatory hypothesis in MDD, including the detailed blood, BOS tests, along with more comprehensive neuroimaging parameters on the brain pathways, might provide more effective results.  


References

  • 1. Guilbert J. The world health report 2002–reducing risks, promoting healthy life. Educ Health. 2003;16:230. PMID: 14741909.
  • 2. Bierhaus A, Wolf J, Andrassy M, Rohleder N, Humpert PM, Petrov D, et al. A mechanism converting psychosocial stress into mononuclear cell activation. Proc Natl Acad Sci USA. 2003;100:1920-5. PMID: 12578963.
  • 3. Aschbacher K, Epel E, Wolkowitz O, Prather A, Puterman E, Dhabhar F. Maintenance of a positive outlook during acute stress protects against pro-inflammatory reactivity and future depressive symptoms. Brain Behav Immun. 2012;26:346-52. PMID: 22119400.
  • 4. Krishnan V, Nestler EJ. The molecular neurobiology of depression. Nature. 2008; 455:894-902. PMID: 18923511.
  • 5. 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. PMID: 29604382.
  • 6. Carvalho L, Torre J, Papadopoulos A, Poon L, Juruena M, Markopoulou K, et al. Lack of clinical therapeutic benefit of antidepressants is associated overall activation of the inflammatory system. J Affect Disorder. 2013;148:136-40. PMID: 23200297.
  • 7. Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry. 2009;65:732-41. PMID: 19150053.
  • 8. Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006;27:24-31. PMID: 16316783.
  • 9. Yulug B. Neuroprotective treatment strategies for poststroke mood disorders: A minireview on atypical neuroleptic drugs and selective serotonin re-uptake inhibitors. Brain Res Bull. 2009;80:95-9. PMID: 19576272.
  • 10. Yuluğ B, Ozan E, Kilic E. Brain-derived neurotrophic factor polymorphism as a genetic risk for depression? A short review of the literature. J Neuropsychiatry Clin Neurosci. 2010;22:123. E5-6. PMID: 20160224.
  • 11. Lapchak PA, Zhang JH. Neuroprotective therapy for stroke and ischemic disease. Switzerland: Springer International Publishing, 2017. p. 607-20. doi:10.1007/978-3-319-45345-3.
  • 12. Cai L, Xu L, Wei L, Chen W. Relationship of mean platelet volume to MDD: a retrospective study. Shanghai Arch Psychiatry. 2017;29:21-9. PMID: 28769542.
  • 13. Kasama T, Miwa Y, Isozaki T, Odai T, Adachi M, Kunkel SL. Neutrophil-derived cytokines: potential therapeutic targets in inflammation. Curr Drug Targets Inflamm Allergy. 2005;4:273-9. PMID: 16101533.
  • 14. Amodeo G, Trusso MA, Fagiolini A. Depression and inflammation: disentangling a clear yet complex and multifaceted link. Neuropsychiatry. 2017;7:448-57. doi: 10.4172/Neuropsychiatry.1000236
  • 15. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56-62. PMID: 14399272.
  • 16. Akdemir A, Türkçapar M, Örsel S, Demirergi N, Dag I, Özbay M. Reliability and validity of the Turkish version of the Hamilton Depression Rating Scale. Compr Psychiatry. 2001;42:161-5. PMID: 11244153.
  • 17. SPSS I: IBM SPSS statistics for windows. Armonk, New York, USA: IBM SPSS 2013.
  • 18. Liu Y, Ho RC-M, 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 Disorder. 2012;139:230-9. PMID: 21872339.
  • 19. Gimeno D, Kivimäki M, Brunner EJ, Elovainio M, De Vogli R, Steptoe A, et al. Associations of C-reactive protein and interleukin-6 with cognitive symptoms of depression: 12-year follow-up of the Whitehall II study. Psychol Med. 2009;39:413-23. PMID: 18533059.
  • 20. Demircan F, Gözel N, Kılınç F, Ulu R, Atmaca M. The impact of red blood cell distribution width and neutrophil/lymphocyte ratio on the diagnosis of major depressive disorder. Neurol Ther. 2016;5:27-33. PMID: 26686339.
  • 21. Osimo EF, Baxter LJ, Lewis G, Jones PB, Khandaker GM. Prevalence of low-grade inflammation in depression: a systematic review and meta-analysis of CRP levels. Psychol Med. 2019;49:1958-70. PMID: 31258105.
  • 22. Dooley LN, Kuhlman KR, Robles TF, Eisenberger NI, Craske MG, Bower JE. The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. Neurosci Biobehav Rev. 2018;94:219-37. PMID: 30201219.
  • 23. Howren MB, Lamkin DM, Suls J. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med. 2009;71:171-86. PMID: 19188531.
  • 24. Fried EI, Von Stockert S, Haslbeck J, Lamers F, Schoevers R, Penninx B. Using network analysis to examine links between individual depressive symptoms, inflammatory markers, and covariates. Psychol Med. 2020;50:2682-90. PMID: 31615595.
  • 25. Maes M, Van de Vyvere J, Vandoolaeghe E, Bril T, Demedts P, Wauters A, et al. Alterations in iron metabolism and the erythron in major depression: further evidence for a chronic inflammatory process. J Affect Disorder. 1996;40:23-33. PMID: 8882911.
  • 26. Raison CL, Rutherford RE, Woolwine BJ, Shuo C, Schettler P, Drake DF, et al. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry 2013;70:31-41. PMID: 22945416.
  • 27. Uher R, Tansey KE, Dew T, Maier W, Mors O, Hauser J, et al. An inflammatory biomarker as a differential predictor of outcome of depression treatment with escitalopram and nortriptyline. Am J Psychiatry. 2014;171:1278-86. PMID: 25017001.
  • 28. Meng G, Wang L, Wang X, Chi VTQ, Zhang Q, Liu L, et al. Association between neutrophil to lymphocyte ratio and depressive symptoms among Chinese adults: a population study from the TCLSIH cohort study. Psychoneuroendocrinology. 2019;103:76-82. PMID: 30658341.
  • 29. Islam MR, Islam MR, Ahmed I, Moktadir AA, Nahar Z, Islam MS, et al. Elevated serum levels of malondialdehyde and cortisol are associated with major depressive disorder: a case-control study. SAGE Open Med. 2018;6:2050312118773953. PMID: 29770218.
  • 30. Alenko A, Markos Y, Fikru C, Tadesse E, Gedefaw L. Association of serum cortisol level with severity of depression and improvement in newly diagnosed patients with major depressive disorder in Jimma medical center, Southwest Ethiopia. Plos One. 2020;15:e0240668. PMID: 33064754.
  • 31. Haroon E, Woolwine BJ, Chen X, Pace TW, Parekh S, Spivey JR, et al. IFN-alpha-induced cortical and subcortical glutamate changes assessed by magnetic resonance spectroscopy. Neuropsychopharmacology. 2014;39:1777-85. PMID: 24481242.
  • 32. Miller AH, Raison CL. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol. 2016;16:22-34. PMID: 26711676.
  • 33. Shafiee M, Tayefi M, Hassanian SM, Ghaneifar Z, Parizadeh MR, Avan A, et al. Depression and anxiety symptoms are associated with white blood cell count and red cell distribution width: a sex-stratified analysis in a population-based study. Psychoneuroendocrinology. 2017;84:101-8. PMID: 28697416.
There are 33 citations in total.

Details

Primary Language English
Subjects ​Internal Diseases
Journal Section Research Article
Authors

Abdullah Burak Uygur 0000-0001-7056-7553

Şeyda Çankaya 0000-0001-5309-0351

Publication Date August 30, 2021
Submission Date February 14, 2021
Acceptance Date April 22, 2021
Published in Issue Year 2021 Volume: 5 Issue: 2

Cite

Vancouver Uygur AB, Çankaya Ş. The relationship between the changes in inflammatory parameters and response to treatment in major depression patients starting antidepressant treatment. Acta Med. Alanya. 2021;5(2):118-25.

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