Cytokines in agitated and non-agitated patients admitted to an acute psychiatric department: A cross-sectional study


Autoři: Jeanette Brun Larsen aff001;  Astrid Kamilla Stunes aff003;  Arne Vaaler aff001;  Solveig Klæbo Reitan aff001
Působiště autorů: St. Olav’s University Hospital, Department of Mental Health, Trondheim, Norway aff001;  Norwegian University of Science and Technology, Faculty of Medicine and Health Science, Department of Mental Health, Trondheim, Norway aff002;  Norwegian University of Science and Technology, Faculty of Medicine and Health Science, Department of Clinical and Molecular Medicine, Trondheim, Norway aff003;  St. Olav’s University Hospital, Medical Clinic, Trondheim, Norway aff004
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0222242

Souhrn

Background

Different psychiatric diagnostic groups have been reported to have cytokine levels deviating from healthy controls. In acute clinical settings however, the specific challenging symptoms and signs are more important than a diagnostic group. Thus, exploration of cytokines and immune activity and their role in specific symptoms is important. Reports in this field so far are sparse.

Objective

In the present study, we aimed to examine the association between immune activity measured as levels of cytokines and agitation (independent of diagnostic group) in patients admitted to an acute psychiatric inpatient department.

Methods

A total of 316 patients admitted to an acute psychiatric inpatient department were included. Thirty-nine patients with psychosis were subject to subgroup analyses. Agitation was assessed by the Positive and Negative Syndrome Scale, Excitement Component (PANSS-EC). Based on PANNS-EC patients were stratified into two groups: 67 agitated patients and 249 non-agitated patients. Serum concentrations of the following immune markers were measured: interleukin (IL) -1β, IL-4, IL-6, IL-10, tumor necrosis factor (TNF) -α, interferon (IFN) -γ and transforming growth factor (TGF) -β.

Results

Serum levels of TNF-α were significantly higher in patients with agitation compared to those without, both when all patients were included in the analyses (p = 0.004) and in the psychosis group (p = 0.027). After correcting for multiple testing, only the findings in the total population remained significant.

Conclusions

Our findings suggest an association between TNF-α and agitation in an acute psychiatric population. A similar trend was reproduced to the psychosis subgroup. This suggests that agitation might be an independent entity associated with cytokines across different diagnostic groups.

Klíčová slova:

Biology and life sciences – Physiology – Developmental biology – Molecular development – Psychology – Behavior – Aggression – Biochemistry – Proteins – Interferons – Medicine and health sciences – Immune physiology – Immunology – Immune system – Innate immune system – Cytokines – Immune response – Inflammation – Mental health and psychiatry – Psychoses – Schizophrenia – Health care – Patients – Inpatients – Diagnostic medicine – Signs and symptoms – Pathology and laboratory medicine – Social sciences


Zdroje

1. Kiecolt-Glaser JK, Derry HM, Fagundes CP. Inflammation: depression fans the flames and feasts on the heat. The American journal of psychiatry. 2015;172(11):1075–91. Epub 2015/09/12. doi: 10.1176/appi.ajp.2015.15020152 26357876.

2. Goldsmith DR, Rapaport MH, Miller BJ. A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression. Mol Psychiatry. 2016;21(12):1696–709. Epub 2016/02/24. doi: 10.1038/mp.2016.3 26903267.

3. Girgis RR, Kumar SS, Brown AS. The Cytokine Model of Schizophrenia: Emerging Therapeutic Strategies. Biol Psychiatry. 2014;75(4):292–9. http://dx.doi.org/10.1016/j.biopsych.2013.12.002. 24439555

4. Bluthe RM, Castanon N, Pousset F, Bristow A, Ball C, Lestage J, et al. Central injection of IL-10 antagonizes the behavioural effects of lipopolysaccharide in rats. Psychoneuroendocrinology. 1999;24(3):301–11. Epub 1999/04/02. 10101735.

5. Schmidt FM, Schroder T, Kirkby KC, Sander C, Suslow T, Holdt LM, et al. Pro- and anti-inflammatory cytokines, but not CRP, are inversely correlated with severity and symptoms of major depression. Psychiatry research. 2016;239:85–91. Epub 2016/05/04. doi: 10.1016/j.psychres.2016.02.052 27137966.

6. Dahan S, Bragazzi NL, Yogev A, Bar-Gad M, Barak V, Amital H, et al. The relationship between serum cytokine levels and degree of psychosis in patients with schizophrenia. Psychiatry research. 2018;268:467–72. Epub 2018/08/24. doi: 10.1016/j.psychres.2018.07.041 30138859.

7. Zeller SL, Rhoades RW. Systematic reviews of assessment measures and pharmacologic treatments for agitation. Clin Ther. 2010;32(3):403–25. Epub 2010/04/20. doi: 10.1016/j.clinthera.2010.03.006 20399981.

8. San L, Marksteiner J, Zwanzger P, Figuero MA, Romero FT, Kyropoulos G, et al. State of Acute Agitation at Psychiatric Emergencies in Europe: The STAGE Study. Clin Pract Epidemiol Ment Health. 2016;12:75–86. Epub 2016/11/20. doi: 10.2174/1745017901612010075 27857778.

9. Serrano-Blanco A, Rubio-Valera M, Aznar-Lou I, Baladon Higuera L, Gibert K, Gracia Canales A, et al. In-patient costs of agitation and containment in a mental health catchment area. BMC Psychiatry. 2017;17(1):212. Epub 2017/06/07. doi: 10.1186/s12888-017-1373-4 28583103.

10. Garriga M, Pacchiarotti I, Kasper S, Zeller SL, Allen MH, Vazquez G, et al. Assessment and management of agitation in psychiatry: Expert consensus. World J Biol Psychiatry. 2016;17(2):86–128. Epub 2016/02/26. doi: 10.3109/15622975.2015.1132007 26912127.

11. Barzilay R, Lobel T, Krivoy A, Shlosberg D, Weizman A, Katz N. Elevated C-reactive protein levels in schizophrenia inpatients is associated with aggressive behavior. Eur Psychiatry. 2016;31:8–12. Epub 2015/12/15. doi: 10.1016/j.eurpsy.2015.09.461 26657596.

12. Pan S, Tan Y, Yao S, Zhao X, Xiong J. Serum high-sensitivity C-reactive protein: A delicate sentinel elevated in drug-free acutely agitated patients with schizophrenia. Psychiatry research. 2016;246:89–94. Epub 2016/09/27. doi: 10.1016/j.psychres.2016.09.033 27669496.

13. Li H, Zhang Q, Li N, Wang F, Xiang H, Zhang Z, et al. Plasma levels of Th17-related cytokines and complement C3 correlated with aggressive behavior in patients with schizophrenia. Psychiatry research. 2016;246:700–6. http://dx.doi.org/10.1016/j.psychres.2016.10.061. 27829509

14. Das S, Deuri SK, Sarmah A, Pathak K, Baruah A, Sengupta S, et al. Aggression as an independent entity even in psychosis- the role of inflammatory cytokines. Journal of neuroimmunology. 2016;292:45–51. Epub 2016/03/06. doi: 10.1016/j.jneuroim.2016.01.012 26943958.

15. WHO. World Health Organization: The ICD-10 classification of mental and behavioural disorders: diagnostic criteria for research. Geneva1993.

16. Montoya A, Valladares A, Lizan L, San L, Escobar R, Paz S. Validation of the Excited Component of the Positive and Negative Syndrome Scale (PANSS-EC) in a naturalistic sample of 278 patients with acute psychosis and agitation in a psychiatric emergency room. Health and quality of life outcomes. 2011;9:18. Epub 2011/03/31. doi: 10.1186/1477-7525-9-18 21447155.

17. Citrome L. Comparison of intramuscular ziprasidone, olanzapine, or aripiprazole for agitation: a quantitative review of efficacy and safety. J Clin Psychiatry. 2007;68(12):1876–85. Epub 2007/12/29. 18162018.

18. Allen MH, Citrome L, Pikalov A, Hsu J, Loebel A. Efficacy of lurasidone in the treatment of agitation: A post hoc analysis of five short-term studies in acutely ill patients with schizophrenia. Gen Hosp Psychiatry. 2017;47:75–82. Epub 2017/08/16. doi: 10.1016/j.genhosppsych.2017.05.002 28807142.

19. Corsi-Zuelli F, Loureiro CM, Shuhama R, Fachim HA, Menezes PR, Louzada-Junior P, et al. Cytokine profile in first-episode psychosis, unaffected siblings and community-based controls: the effects of familial liability and childhood maltreatment. Psychol Med. 2019:1–9. Epub 2019/05/09. doi: 10.1017/s0033291719001016 31064423.

20. Janicki-Deverts D, Cohen S, Doyle WJ. Cynical hostility and stimulated Th1 and Th2 cytokine production. Brain Behav Immun. 2010;24(1):58–63. Epub 2009/08/04. doi: 10.1016/j.bbi.2009.07.009 19647069.

21. Friedman EM, Reyes TM, Coe CL. Context-dependent behavioral effects of interleukin-1 in the rhesus monkey (Macaca mulatta). Psychoneuroendocrinology. 1996;21(5):455–68. Epub 1996/07/01. 8888368.

22. Shelton RC, Miller AH. Eating ourselves to death (and despair): the contribution of adiposity and inflammation to depression. Prog Neurobiol. 2010;91(4):275–99. Epub 2010/04/27. doi: 10.1016/j.pneurobio.2010.04.004 20417247.

23. Kanneganti TD, Dixit VD. Immunological complications of obesity. Nature immunology. 2012;13(8):707–12. Epub 2012/07/21. doi: 10.1038/ni.2343 22814340.

24. Tsai SY, Chung KH, Wu JY, Kuo CJ, Lee HC, Huang SH. Inflammatory markers and their relationships with leptin and insulin from acute mania to full remission in bipolar disorder. Journal of affective disorders. 2012;136(1–2):110–6. Epub 2011/10/04. doi: 10.1016/j.jad.2011.08.022 21962564.

25. 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. Epub 2012/12/04. doi: 10.1016/j.pnpbp.2012.11.009 23200828.

26. Jha MK, Miller AH, Minhajuddin A, Trivedi MH. Association of T and non-T cell cytokines with anhedonia: Role of gender differences. Psychoneuroendocrinology. 2018;95:1–7. Epub 2018/05/22. doi: 10.1016/j.psyneuen.2018.05.017 29783087.

27. Roge R, Moller BK, Andersen CR, Correll CU, Nielsen J. Immunomodulatory effects of clozapine and their clinical implications: what have we learned so far? Schizophrenia research. 2012;140(1–3):204–13. Epub 2012/07/27. doi: 10.1016/j.schres.2012.06.020 22831769.


Článek vyšel v časopise

PLOS One


2019 Číslo 9
Nejčtenější tento týden