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Cytokine concentrations are related to level of mental distress in inpatients not using anti-inflammatory drugs

  • Helge Toft (a1) (a2), Lars Lien (a1) (a3), Sudan P. Neupane (a1) (a4), Dawit S. Abebe (a1) (a5), Terje Tilden (a6), Bruce E. Wampold (a6) (a7) and Jørgen G. Bramness (a1) (a8)...

Abstract

Objective:

Cross-sectional data show elevated levels of circulating cytokines in psychiatric patients. The literature is divided concerning anti-inflammatory drugs’ ability to relieve symptoms, questioning a causal link between inflammatory pathways and psychiatric conditions. We hypothesised that the development of circulating cytokine levels is related to mental distress, and that this relationship is affected by the use of anti-inflammatory drugs.

Methods:

The study was a longitudinal assessment of 12-week inpatient treatment at Modum Bad Psychiatric Center, Norway. Sera and self-reported Global Severity Index (GSI) scores, which measure psychological distress, were collected at admission (T0), halfway (T1) and before discharge (T2). Other variables known to distort the neuroimmune interplay were included. These were age, gender, diagnosis of PTSD, antidepressants and anti-inflammatory drugs. A total of 128 patients (92 women and 36 men) were included, and 28 were using anti-inflammatory medication. Multilevel modelling was used for data analysis.

Results:

Patients with higher levels of IL-1RA and MCP-1 had higher GSI scores (p = 0.005 and p = 0.020). PTSD patients scored higher on GSI than non-PTSD patients (p = 0.002). These relationships were mostly present among those not using anti-inflammatory drugs (n = 99), with higher levels of IL-1RA and MCP-1 being related to higher GSI score (p = 0.023 and 0.018, respectively). Again, PTSD patients showed higher GSI levels than non-PTSD patients (p = 0.014).

Conclusions:

Cytokine levels were associated with level of mental distress as measured by the GSI scores, but this relationship was not present among those using anti-inflammatory drugs. We found no association between cytokine levels and development of GSI score over time.

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Copyright

This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

Corresponding author

Author for correspondence: Helge Toft. E-mail: helge.toft@sykehuset-innlandet.no

References

Hide All
Baune, BT (2017) Are non-steroidal anti-inflammatory drugs clinically suitable for the treatment of symptoms in depression-associated inflammation? Current Topics in Behavioral Neurosciences 31, 303319.
Bech, P, Bille, J, Moller, SB, Hellstrom, LC and Ostergaard, SD (2014) Psychometric validation of the Hopkins Symptom Checklist (SCL-90) subscales for depression, anxiety, and interpersonal sensitivity. Journal of Affective Disorders 160, 98103.
Belchamber, K, Hall, DA and Hourani, SM (2014) Smoking enhances the proinflammatory effects of nucleotides on cytokine release from human lung. PloS One 9, e99711.
Bell, JA, Kivimaki, M, Bullmore, ET, Steptoe, A, Consortium, MRCI and Carvalho, LA (2017) Repeated exposure to systemic inflammation and risk of new depressive symptoms among older adults. Transl Psychiatry 7, e1208.
Calder, PC, Ahluwalia, N, Brouns, F, Buetler, T, Clement, K, Cunningham, K, Esposito, K, Jonsson, LS, Kolb, H, Lansink, M, Marcos, A, Margioris, A, Matusheski, N, Nordmann, H, O’brien, J, Pugliese, G, Rizkalla, S, Schalkwijk, C, Tuomilehto, J, Warnberg, J, Watzl, B and Winklhofer-Roob, BM (2011 ) Dietary factors and low-grade inflammation in relation to overweight and obesity. British Journal of Nutrition 106 (Suppl. 3), S5S78.
Campbell, RA, Vieira-De-Abreu, A, Rowley, JW, Franks, ZG, Manne, BK, Rondina, MT, Kraiss, LW, Majersik, JJ, Zimmerman, GA and Weyrich, AS (2017) Clots are potent triggers of inflammatory cell gene expression: indications for timely fibrinolysis. Arteriosclerosis, Thrombosis, and Vascular Biology 37, 18191827.
Canivet, C, Menasria, R, Rheaume, C, Piret, J and Boivin, G (2015) Valacyclovir combined with artesunate or rapamycin improves the outcome of herpes simplex virus encephalitis in mice compared to antiviral therapy alone. Antiviral Research 123, 105113.
Curran, PJ and Bauer, DJ (2011) The disaggregation of within-person and between-person effects in longitudinal models of change. Annual Review of Psychology 62, 583619.
Dahl, J, Ormstad, H, Aass, HC, Malt, UF, Bendz, LT, Sandvik, L, Brundin, L and Andreassen, OA (2014) The plasma levels of various cytokines are increased during ongoing depression and are reduced to normal levels after recovery. Psychoneuroendocrinology 45, 7786.
Dahl, J, Ormstad, H, Aass, HC, Sandvik, L, Malt, UF and Andreassen, OA (2016) Recovery from major depressive disorder episode after non-pharmacological treatment is associated with normalized cytokine levels. Acta Psychiatrica Scandinavica 134, 4047.
Dalton, B, Bartholdy, S, Robinson, L, Solmi, M, Ibrahim, MaA, Breen, G, Schmidt, U and Himmerich, H (2018) A meta-analysis of cytokine concentrations in eating disorders. Journal of Psychiatric Research 103, 252264.
Dantzer, R, O’connor, JC, Freund, GG, Johnson, RW and Kelley, KW (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nature Reviews: Neuroscience 9, 4656.
Derogatis, L, Lipman, R and Covi, L (1973) SCL-90. Psychopharmacology Bulletin 9, 1328.
Dixit, VD, Yang, H, Sayeed, KS, Stote, KS, Rumpler, WV, Baer, DJ, Longo, DL, Mattson, MP and Taub, DD (2011) Controlled meal frequency without caloric restriction alters peripheral blood mononuclear cell cytokine production. Journal of Inflammation 8, 1.
Dowlati, Y, Herrmann, N, Swardfager, W, Liu, H, Sham, L, Reim, EK and Lanctôt, KL (2010) A meta-analysis of cytokines in major depression. Biological Psychiatry 67, 446457.
Eyre, HA, Air, T, Proctor, S, Rositano, S and Baune, BT (2015) A critical review of the efficacy of non-steroidal anti-inflammatory drugs in depression. Progress in Neuropsychopharmacology & Biological Psychiatry 57, 1116.
Furtado, M and Katzman, MA (2015) Neuroinflammatory pathways in anxiety, posttraumatic stress, and obsessive compulsive disorders. Psychiatry Research 229, 3748.
Holub, M, Lawrence, DA, Andersen, N, Davidová, A, Beran, O, Marešová, V and Chalupa, P. (2013) Cytokines and chemokines as biomarkers of community-acquired bacterial infection. Mediators of Inflammation 2013, 7.
Kim, YK, Amidfar, M and Won, E (2019) A review on inflammatory cytokine-induced alterations of the brain as potential neural biomarkers in post-traumatic stress disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry 91, 103112.
Köhler, O, Benros, ME, Nordentoft, M, Farkouh, ME, Iyengar, RL, Mors, O and Krogh, J (2014) Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials. JAMA Psychiatry 71, 13811391.
Köhler, O, Krogh, J, Mors, O and Benros, ME (2016) Inflammation in depression and the potential for anti-inflammatory treatment. Current Neuropharmacology 14, 732742.
Kornstein, SG and Schneider, RK (2001) Clinical features of treatment-resistant depression. Journal of Clinical Psychiatry 62 (Suppl. 16), 1825.
Leemasawatdigul, K and Gappa-Fahlenkamp, H (2011) Effect of storage conditions on the stability of recombinant human MCP-1/CCL2. Biologicals: Journal of the International Association of Biological Standardization 39, 2932.
Little, RJA (1988) A test of missing completely at random for multivariate data with missing values. Journal of the American Statistical Association 83, 11981202.
Maes, M (1995) Evidence for an immune response in major depression: a review and hypothesis. Progress in Neuro-Psychopharmacology and Biological Psychiatry 19, 1138.
Maes, M (2011) Depression is an inflammatory disease, but cell-mediated immune activation is the key component of depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry 35, 664675.
Maes, M, Bosmans, E, De, Jongh R, Kenis, G, Vandoolaeghe, E and Neels, H (1997) Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment resistant depression. Cytokine 9, 853858.
Maes, M, Bosmans, E, Suy, E, Vandervorst, C, De, Jonckheere C and Raus, J (1990) Immune disturbances during major depression: upregulated expression of Interleukin-2 receptors. Neuropsychobiology 24, 115120.
Miller, AH and Raison, CL (2016) The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nature Reviews: Immunology 16, 2234.
Miller, MW, Lin, AP, Wolf, EJ and Miller, DR (2018) Oxidative stress, inflammation, and neuroprogression in chronic PTSD. Harvard Review of Psychiatry 26, 5769.
Morch, RH, Dieset, I, Faerden, A, Hope, S, Aas, M, Nerhus, M, Gardsjord, ES, Haram, M, Falk, RS, Joa, I, Morken, G, Agartz, I, Aukrust, P, Djurovic, S, Melle, I, Ueland, T and Andreassen, OA (2017) Persistent increase in TNF and IL-1 markers in severe mental disorders suggests trait-related inflammation: a one year follow-up study. Acta Psychiatrica Scandinavica 136, 400408.
Müller, N, Schwarz, MJ, Dehning, S, Douhe, A, Cerovecki, A, Goldstein-Müller, B, Spellmann, I, Hetzel, G, Maino, K, Kleindienst, N, Möller, HJ, Arolt, V and Riedel, M (2006) The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Molecular Psychiatry 11, 680.
Passos, IC, Vasconcelos-Moreno, MP, Costa, LG, Kunz, M, Brietzke, E, Quevedo, J, Salum, G, Magalhaes, PV, Kapczinski, F and Kauer-Sant’anna, M (2015) Inflammatory markers in post-traumatic stress disorder: a systematic review, meta-analysis, and meta-regression. Lancet Psychiatry 2, 10021012.
Pedersen, G and Karterud, S (2004) Is SCL-90R helpful for the clinician in assessing DSM-IV symptom disorders? Acta Psychiatrica Scandinavica 110, 215224.
Phillips, C and Fahimi, A (2018) Immune and neuroprotective effects of physical activity on the brain in depression. Frontiers in Neuroscience 12, 498.
Rabe-Hesketh, S and Skrondal, A (2016) Multilevel and Longitudinal Modeling Using Stata, Volume I: Continuous Responses , 3rd edn. College Station, TX: Stata Press, p. 497.
Raison, CL, Rutherford, RE, Woolwine, BJ, Shuo, C, Schettler, P, Drake, DF, Haroon, E and Miller, AH (2013) A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry 70, 3141.
Rytila-Manninen, M, Frojd, S, Haravuori, H, Lindberg, N, Marttunen, M, Kettunen, K and Therman, S (2016) Psychometric properties of the symptom checklist-90 in adolescent psychiatric inpatients and age- and gender-matched community youth. Child and Adolescent Psychiatry and Mental Health 10, 23.
Schiepers, OJ, Wichers, MC and Maes, M (2005) Cytokines and major depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry 29, 201217.
Sheehan, DV, Lecrubier, Y, Sheehan, KH, Amorim, P, Janavs, J, Weiller, E, Hergueta, T, Baker, R and Dunbar, GC (1998) The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. Journal of Clinical Psychiatry 59 (Suppl. 20), 2233; quiz 34–57.
Smith, RS (1991) The macrophage theory of depression. Medical Hypotheses 35, 298306.
Toft, H, Bramness, JG, Lien, L, Abebe, DS, Wampold, BE, Tilden, T, Hestad, K and Neupane, SP (2018) PTSD patients show increasing cytokine levels during treatment despite reduced psychological distress. Neuropsychiatric Disease and Treatment 14, 23672378.
Valkanova, V, Ebmeier, KP and Allan, CL (2013) CRP, IL-6 and depression: a systematic review and meta-analysis of longitudinal studies. Journal of Affective Disorders 150, 736744.
Van Den Biggelaar, AH, Gussekloo, J, De Craen, AJ, Frolich, M, Stek, ML, Van Der Mast, RC and Westendorp, RG (2007) Inflammation and interleukin-1 signaling network contribute to depressive symptoms but not cognitive decline in old age. Experimental Gerontology 42, 693701.
Virtanen, M, Shipley, MJ, Batty, GD, Hamer, M, Allan, CL, Lowe, GD, Ebmeier, KP, Akbaraly, TN, Alenius, H, Haapakoski, R, Singh-Manoux, A and Kivimäki, M (2015) Interleukin-6 as a predictor of symptom resolution in psychological distress: a cohort study. Psychological Medicine 45, 21372144.
Vogelzangs, N, De Jonge, P, Smit, JH, Bahn, S and Penninx, BW (2016) Cytokine production capacity in depression and anxiety. Transl Psychiatry 6, e825.
Waheed, A, Dalton, B, Wesemann, U, Ibrahim, MaA and Himmerich, H (2018) A systematic review of interleukin-1beta in post-traumatic stress disorder: evidence from human and animal studies. Journal of Interferon and Cytokine Research 38, 111.
Wang, Z, Caughron, B and Young, MRI (2017) Posttraumatic stress disorder: an immunological disorder? Frontiers in Psychiatry 8, 222.
Warner-Schmidt, JL, Chen, EY, Marshall, JJ, Greengard, P and Vanover, KE (2011) Antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated by antiinflammatory drugs in mice and humans. Proceedings of the National Academy of Sciences of the United States of America 108, 92629267.
Williams, JR (2008) The declaration of Helsinki and public health. Bulletin of the World Health Organization 86, 650652.
Young, JJ, Bruno, D and Pomara, N (2014) A review of the relationship between proinflammatory cytokines and major depressive disorder. Journal of Affective Disorders 169, 1520.

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Cytokine concentrations are related to level of mental distress in inpatients not using anti-inflammatory drugs

  • Helge Toft (a1) (a2), Lars Lien (a1) (a3), Sudan P. Neupane (a1) (a4), Dawit S. Abebe (a1) (a5), Terje Tilden (a6), Bruce E. Wampold (a6) (a7) and Jørgen G. Bramness (a1) (a8)...

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