Association between Proinflammatory Cytokines and Anxiety and Depression Symptoms in Rheumatoid Arthritis Patients: A Cross-sectional Study

Background: Rheumatoid arthritis (RA) patients have a greater prevalence of anxiety and depression. Proinflammatory cytokines are elevated in RA. We aim to evaluate the association between systemic inflammation in RA and anxiety and depression. Methods: There were 31 RA patients, 16 with active disease activity and 15 in remission state; they were assessed using the Hospital Anxiety and Depression Scale and for RA disease activity using Disease Activity Score of 28 joints (DAS28) – CRP (C-reactive protein). Serum proinflammatory cytokines were measured, including interleukin (IL)-6, IL-17, and Tumour Necrosis Factor-alpha (TNF-α). Results: Among 31 patients, ten patients showed anxiety symptoms, 19 patients showed depression symptoms, and two displayed mixed symptoms. Serum TNF-α levels were significantly higher in active disease than in the remission group (p-value 0.006). There was no association or correlation between proinflammatory cytokines to anxiety and depression symptoms in the active disease and remission groups. Conclusion: This suggests that other factors besides disease activity and state of systemic inflammation may cause anxiety and depression in RA patients.

[1]  M. R. Pereira,et al.  A Systematic Review of Nutritional Interventions on Key Cytokine Pathways in Rheumatoid Arthritis and Its Implications for Comorbid Depression: Is a More Comprehensive Approach Required? , 2022, Cureus.

[2]  Xuesong Liu,et al.  Serum tumor necrosis factor‐α, interleukin‐1β, interleukin‐6, and interleukin‐17 relate to anxiety and depression risks to some extent in non‐small cell lung cancer survivor , 2021, The clinical respiratory journal.

[3]  Chunhai Zhang.  Flare-up of cytokines in rheumatoid arthritis and their role in triggering depression: Shared common function and their possible applications in treatment (Review) , 2020, Biomedical reports.

[4]  C. Edwards,et al.  Rheumatoid Arthritis: The Impact of Mental Health on Disease: A Narrative Review , 2020, Rheumatology and Therapy.

[5]  Alexey P Sarapultsev,et al.  Low glucocorticoids in stress-related disorders: the role of inflammation , 2020, Stress.

[6]  P. Narongroeknawin,et al.  Prevalence of and factors associated with depression and anxiety in patients with rheumatoid arthritis: A multicenter prospective cross‐sectional study , 2020, International journal of rheumatic diseases.

[7]  S. Hider,et al.  The association between anxiety and disease activity and quality of life in rheumatoid arthritis: a systematic review and meta-analysis , 2020, Clinical Rheumatology.

[8]  Pei Yang,et al.  Th17 cell pathogenicity and plasticity in rheumatoid arthritis , 2019, Journal of leukocyte biology.

[9]  S. Korte,et al.  Fatigue in inflammatory rheumatic disorders: pathophysiological mechanisms , 2019, Rheumatology.

[10]  A. Fresán,et al.  Prevalence for and Factors Associated With Depression and Anxiety Symptoms in Mexican Patients With Rheumatoid Arthritis. , 2019, Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases.

[11]  M. Harth,et al.  Pain and affective distress in arthritis: relationship to immunity and inflammation , 2019, Expert review of clinical immunology.

[12]  I. McInnes,et al.  Rheumatoid arthritis and depression: an inflammatory perspective. , 2019, The lancet. Psychiatry.

[13]  S. Suhardjono,et al.  Anxiety and depression among caregivers of hemodialysis patients at the Indonesian national referral hospital , 2018, Medical Journal of Indonesia.

[14]  E. Favalli,et al.  Sarilumab: patient-reported outcomes in rheumatoid arthritis , 2018, Patient related outcome measures.

[15]  M. Bernardes,et al.  Influence of Biological Therapeutics, Cytokines, and Disease Activity on Depression in Rheumatoid Arthritis , 2018, Journal of immunology research.

[16]  E. Choy,et al.  Neuroendocrine and neurophysiological effects of interleukin 6 in rheumatoid arthritis , 2017, Rheumatology.

[17]  Milena Flória-Santos,et al.  Elevated serum levels of proinflammatory cytokines potentially correlate with depression and anxiety in colorectal cancer patients in different stages of the antitumor therapy , 2017, Cytokine.

[18]  Naomi M Simon,et al.  Depression, inflammation, and epidermal growth factor receptor (EGFR) status in metastatic non-small cell lung cancer: A pilot study. , 2017, Journal of psychosomatic research.

[19]  U. Vogel,et al.  Systematic review and meta-analysis: pharmacogenetics of anti-TNF treatment response in rheumatoid arthritis , 2017, The Pharmacogenomics Journal.

[20]  S. Patten,et al.  Systematic Review and Meta-analysis of Interventions for Depression and Anxiety in Persons With Rheumatoid Arthritis , 2017, Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases.

[21]  P. Miossec,et al.  Selected cytokine pathways in rheumatoid arthritis , 2017, Seminars in Immunopathology.

[22]  J. Sturgeon,et al.  Affective disturbance in rheumatoid arthritis: psychological and disease-related pathways , 2016, Nature Reviews Rheumatology.

[23]  K. Michaud,et al.  Patient-Reported Outcomes in Rheumatoid Arthritis. , 2016, Rheumatic diseases clinics of North America.

[24]  K. Stein,et al.  Tumour necrosis factor-α inhibitor therapy in chronic physical illness: A systematic review and meta-analysis of the effect on depression and anxiety. , 2015, Journal of psychosomatic research.

[25]  A. F. Stern.  The hospital anxiety and depression scale. , 2014, Occupational medicine.

[26]  J. Wolchok,et al.  Depression, cytokines, and pancreatic cancer , 2014, Psycho-oncology.

[27]  M. Irwin,et al.  From stress to inflammation and major depressive disorder: a social signal transduction theory of depression. , 2014, Psychological bulletin.

[28]  Q. Luo,et al.  Sputum interleukin-6, tumor necrosis factor-α and Salivary cortisol as new biomarkers of depression in lung cancer patients , 2013, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[29]  M. Hotopf,et al.  The prevalence of depression in rheumatoid arthritis: a systematic review and meta-analysis , 2013, Rheumatology.

[30]  R. Ho,et al.  The role of interleukin (IL)‐17 in anxiety and depression of patients with rheumatoid arthritis , 2012, International journal of rheumatic diseases.

[31]  A. Bruno,et al.  [Comparation of levels of anxiety and depression in patients with autoimmune and chronic-degenerative rheumatic: preliminary data]. , 2011, Reumatismo.

[32]  E. Yelin,et al.  Depression in patients with rheumatoid arthritis: description, causes and mechanisms. , 2011, International journal of clinical rheumatology.

[33]  N. Herrmann,et al.  A Meta-Analysis of Cytokines in Major Depression , 2010, Biological Psychiatry.

[34]  T. Furukawa,et al.  Depression, inflammation, and pain in patients with rheumatoid arthritis. , 2009, Arthritis and rheumatism.

[35]  A. Altamura,et al.  Cytokine Polymorphisms in the Pathophysiology of Mood Disorders , 2009, CNS Spectrums.

[36]  T. Matsui,et al.  Disease Activity Score 28 (DAS28) using C-reactive protein underestimates disease activity and overestimates EULAR response criteria compared with DAS28 using erythrocyte sedimentation rate in a large observational cohort of rheumatoid arthritis patients in Japan , 2007, Annals of the rheumatic diseases.

[37]  N. Nishimoto.  Interleukin-6 in rheumatoid arthritis , 2006, Current opinion in rheumatology.

[38]  M. Wichers,et al.  Cytokines and major depression , 2005, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[39]  J. E. Hewett,et al.  Anxiety in rheumatoid arthritis. , 2004, Arthritis and rheumatism.

[40]  H. Anisman,et al.  Cytokines, stress and depressive illness: brain‐immune interactions , 2003, Annals of medicine.

[41]  Michael Maes.  Cytokines in major depression , 1994, Biological Psychiatry.

[42]  A. Zigmond,et al.  The Hospital Anxiety and Depression Scale , 1983, Acta psychiatrica Scandinavica.

[43]  R. Shumnalieva,et al.  DEPRESSION ON PATIENTS WITH RHEUMATOID ARTHRITIS , 2023 .

[44]  Kechun Liu,et al.  Environmental Stewardship Resource Desk , 2021 .

[45]  L. Lix,et al.  Physical comorbidities increase the risk of psychiatric comorbidity in immune-mediated inflammatory disease. , 2018, General hospital psychiatry.

[46]  E. Diamandis,et al.  Pancreatic cancer. , 2013, Clinical chemistry.

[47]  Walter Fiers.  Tumour necrosis factor , 1993 .

[48]  J. E. Barone,et al.  A Meta-Analysis , 2022 .