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Decreased percentage of CD4+ lymphocytes expressing chemokine receptors in bipolar disorder

Published online by Cambridge University Press:  14 March 2019

Izabela G. Barbosa ,
Natalia P. Rocha ,
Erica L. Vieira ,
Mehmet A. Camkurt Open the ORCID record for Mehmet A. Camkurt [Opens in a new window] ,
Rodrigo B. Huguet ,
Fabio T. L. Guimarães ,
Gustavo E. de Brito-Melo ,
Vanessa A. Mendonça ,
Moises E. Bauer  and
Antonio L. Teixeira
Izabela G. Barbosa
Affiliation:
Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, Room 281, Belo Horizonte, MG, Brazil
Natalia P. Rocha
Affiliation:
Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, Room 281, Belo Horizonte, MG, Brazil Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, 1941 East Road, Room 3140, Houston, TX 770054, USA
Erica L. Vieira
Affiliation:
Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, Room 281, Belo Horizonte, MG, Brazil
Mehmet A. Camkurt
Affiliation:
Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, 1941 East Road, Room 3140, Houston, TX 770054, USA
Rodrigo B. Huguet
Affiliation:
Instituto de Previdência dos Servidores do Estado de Minas Gerais, Alameda Ezequiel Dias, 225, Santa Efigênia, Belo Horizonte, 30130-110, Brazil
Fabio T. L. Guimarães
Affiliation:
Laboratório de Imunologia, Universidade Federal dos Vales Jequitinhona e Mucuri, Rodovia MGT 367 ‒ Km 583, n° 5000. Alto da Jacuba, Diamantina, 39100-000, Brazil
Gustavo E. de Brito-Melo
Affiliation:
Laboratório de Imunologia, Universidade Federal dos Vales Jequitinhona e Mucuri, Rodovia MGT 367 ‒ Km 583, n° 5000. Alto da Jacuba, Diamantina, 39100-000, Brazil
Vanessa A. Mendonça
Affiliation:
Laboratório de Imunologia, Universidade Federal dos Vales Jequitinhona e Mucuri, Rodovia MGT 367 ‒ Km 583, n° 5000. Alto da Jacuba, Diamantina, 39100-000, Brazil
Moises E. Bauer
Affiliation:
Laboratório de Imunologia do Estresse, Escola de Ciências, Pontifícia Universidade Católica do Rio Grande do Sul, Av. Ipiranga, 6681 Prédio 12a, Porto Alegre, 90619-900, Brazil
Antonio L. Teixeira*
Affiliation:
Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, Room 281, Belo Horizonte, MG, Brazil Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, 1941 East Road, Room 3140, Houston, TX 770054, USA
*
Author for correspondence: Antonio L. Teixeira, Email: altexr@gmail.com
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Abstract

Objective:

Although accumulating evidence supports the hypothesis that immune/inflammatory mechanisms are associated with the pathophysiology of bipolar disorder (BD), data about the profile of chemokines (chemotactic cytokines) and chemokine receptors are still scarce. The current study was designed to evaluate the expression of chemokine receptors on lymphocytes of patients with BD in comparison with controls.

Methods:

Thirty-three patients with type I BD (N = 21 in euthymia; N = 6 in mania/hypomania; N = 6 in depression) and 22 age- and sex-matched controls were subjected to clinical evaluation and peripheral blood draw. The expression of chemokine receptors CCR3, CCR5, CXCR4, and CXCR3 on CD4+ and CD8+ lymphocytes was assessed by flow cytometry.

Results:

Patients with BD had decreased percentage of CD4+CXCR3+ (p = 0.024), CD4+CCR3+ (p = 0.042), and CD4+CCR5+ (0.013) lymphocytes in comparison with controls. The percentage of both CD4+ and CD8+ lymphocytes expressing the chemokine receptor CXCR4 was similar in patients with BD and controls. Likewise, the percentages of CD8+CXCR3+, CD8+CCR3+, and CD8+CCR5+ lymphocytes were similar in patients with BD and controls.

Conclusion:

Our findings reinforce the hypothesis that immune pathways, especially involving CD4+ lymphocytes, are involved in the physiopathology of BD.

Keywords

bipolar disorderchemokine receptorspsychoneuroimmunologylymphocytes
Type
Original Article
Information
Acta Neuropsychiatrica , Volume 31 , Issue 5 , October 2019 , pp. 246 - 251
Copyright
© Scandinavian College of Neuropsychopharmacology 2019 

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References

Ahmad, SF, Ansari, MA, Nadeem, A, Bakheet, SA, Al-ayadhi, LY and Attia, SM (2018) Upregulation of peripheral CXC and CC chemokine receptor expression on CD4+ T cells is associated with immune dysregulation in children with autism. Progress in Neuro-Psychopharmacology & Biological Psychiatry 81, 211–220.CrossRefGoogle ScholarPubMed
Amorim, P (2000) Mini International Neuropsychiatric Interview (MINI): validação de entrevista breve para diagnóstico de transtornos mentais. Revista Brasileira de Psiquiatria 22, 106–115.CrossRefGoogle Scholar
Andreazza, AC, Kauer-Sant’Anna, M, Frey, BN, Bond, DJ, Kapczinski, F, Young, LT, Yatham, LN (2008) Oxidative stress markers in bipolar disorder: a meta-analysis. The Journal of Affective Disorders 111, 135–144.CrossRefGoogle ScholarPubMed
Apel, K and Hirt, H (2004) Reactive oxygen species: metabolism, oxidative stress, and signal transduction. Annual Review of Plant Biology 55, 373–399.CrossRefGoogle ScholarPubMed
Barbosa, IG, Machado-Vieira, R, Soares, JC and Teixeira, AL (2014) The immunology of bipolar disorder. Neuroimmunomodulation 21, 117–122.CrossRefGoogle ScholarPubMed
Barbosa, IG, Rocha, NP, Bauer, ME, de Miranda, AS, Huguet, RB, Reis, HJ, Zunszain, PA, Horowitz, MA, Pariante, CM, Teixeira, AL (2013) Chemokines in bipolar disorder: trait or state? European Archives of Psychiatry and Clinical Neuroscience 263, 159–165.CrossRefGoogle ScholarPubMed
Brietzke, E, Kauer-Sant’Anna, M, Teixeira, AL and Kapczinski, F (2009) Abnormalities in serum chemokine levels in euthymic patients with bipolar disorder. Brain, Behavior, and Immunity 23, 1079–1082.CrossRefGoogle ScholarPubMed
Brown, NC, Andreazza, AC and Young, LT (2014) An updated meta-analysis of oxidative stress markers in bipolar disorder. Psychiatry Research 218, 61–68.CrossRefGoogle ScholarPubMed
Colpo, GD, Leboyer, M, Dantzer, R, Trivedi, MH and Teixeira, AL (2018) Immune-based strategies for mood disorders: facts and challenges. Expert Review of Neurotherapeutics 18, 139–152.CrossRefGoogle ScholarPubMed
da Rocha, FF, Correa, H and Teixeira, AL (2008) Obsessive-compulsive disorder and immunology: a review. Progress in Neuro-Psychopharmacology & Biological Psychiatry 32, 1139–1146.CrossRefGoogle ScholarPubMed
do Prado, CH, Rizzo, LB, Wieck, A, Lopes, RP, Teixeira, AL, Grassi-Oliveira, R, Bauer, ME (2013) Reduced regulatory T cells are associated with higher levels of Th1/TH17 cytokines and activated MAPK in type 1 bipolar disorder. Psychoneuroendocrinology 38, 667–676.CrossRefGoogle ScholarPubMed
El-Sayed, A and Ramy, HA (2006) Immunological changes in patients with mania: changes in cell mediated immunity in a sample from Egyptian patients. The Egyptian Journal of Immunology 13, 79–85.Google Scholar
Elsner, J, Petering, H, Kluthe, C, Kimmig, D, Smolarski, R, Ponath, P, Kapp, A (1998) Eotaxin-2 activates chemotaxis-related events and release of reactive oxygen species via pertussis toxin-sensitive G proteins in human eosinophils. The European Journal of Immunology 28, 2152–2158.3.0.CO;2-G>CrossRefGoogle ScholarPubMed
Gladkevich, A, Kauffman, HF and Korf, J (2004) Lymphocytes as a neural probe: potential for studying psychiatric disorders. Progress in Neuro-Psychopharmacology & Biological Psychiatry 28, 559–576.CrossRefGoogle ScholarPubMed
Griffith, JW, Sokol, CL and Luster, AD (2014) Chemokines and chemokine receptors: positioning cells for host defense and immunity. Annual Review of Immunology 32, 659–702.CrossRefGoogle ScholarPubMed
Groom, JR, Richmond, J, Murooka, TT, Sorensen, EW, Sung, JH, Bankert, K, von Andrian, UH, Moon, JJ, Mempel, TR, Luster, AD (2012) CXCR3 chemokine receptor-ligand interactions in the lymph node optimize CD4+ T helper 1 cell differentiation. Immunity 37, 1091–1103.CrossRefGoogle ScholarPubMed
Hamilton, MAX (1967) Development of a rating scale for primary depressive illness. The British Journal of Clinical Psychology 6, 278–296.CrossRefGoogle ScholarPubMed
Kunz, M, Ceresér, KM, Goi, PD, Fries, GR, Teixeira, AL, Fernandes, BS, Belmonte-de-Abreu, PS, Kauer-Sant'Anna, M, Kapczinski, F, Gama, CS (2011) Serum levels of IL-6, IL-10 and TNF-α in patients with bipolar disorder and schizophrenia: differences in pro-and anti-inflammatory balance. Revista Brasileira de Psiquiatria 33, 268–274.Google ScholarPubMed
Kupka, RW, Nolen, WA, Post, RM, McElroy, SL, Altshuler, LL, Denicoff, KD, Frye, MA, Keck, PE Jr, Leverich, GS, Rush, AJ, Suppes, T, Pollio, C, Drexhage, HA (2002) High rate of autoimmune thyroiditis in bipolar disorder: lack of association with lithium exposure. Biological Psychiatry 51, 305–311.CrossRefGoogle ScholarPubMed
Luster, AD (1998) Chemokines—chemotactic cytokines that mediate inflammation. The New England Journal of Medicine 338, 436–445.CrossRefGoogle ScholarPubMed
Modabbernia, A, Taslimi, S, Brietzke, E and Ashrafi, M (2013) Cytokine alterations in bipolar disorder: a meta-analysis of 30 studies. The British Journal of Psychiatry 74, 15–25.Google ScholarPubMed
Nakatani, N, Hattori, E, Ohnishi, T, Dean, B, Iwayama, Y, Matsumoto, I, Kato, T, Osumi, N, Higuchi, T, Niwa, S, Yoshikawa, T (2006) Genome-wide expression analysis detects eight genes with robust alterations specific to bipolar I disorder: relevance to neuronal network perturbation. Human Molecular Genetics 15, 1949–1962.CrossRefGoogle ScholarPubMed
Nery, FG, Monkul, ES, Hatch, JP, Fonseca, M, Zunta-Soares, GB, Frey, BN, Bowden, CL, Soares, JC (2008) Celecoxib as an adjunct in the treatment of depressive or mixed episodes of bipolar disorder: a double-blind, randomized, placebo-controlled study. Human Psychopharmacology 23, 87–94.CrossRefGoogle ScholarPubMed
Ogłodek, EA, Szota, A, Just, MJ, Moś, D and Araszkiewicz, A (2014) Comparison of chemokines (CCL-5 and SDF-1), chemokine receptors (CCR-5 and CXCR-4) and IL-6 levels in patients with different severities of depression. Pharmacological Reports 66, 920–926.CrossRefGoogle Scholar
Ogłodek, EA, Szota, AM, Just, MJ, Szromek, AR and Araszkiewicz, A (2016) A study of chemokines, chemokine receptors and interleukin-6 in patients with panic disorder, personality disorders and their co-morbidity. Pharmacological Reports 68, 756–763.CrossRefGoogle ScholarPubMed
Panizzutti, B, Gubert, C, Schuh, AL, Ferrari, P, Bristot, G, Fries, GR, Massuda, R, Walz, J, Rocha, NP, Berk, M, Teixeira, AL, Gama, CS (2015) Increased serum levels of eotaxin/CCL11 in late-stage patients with bipolar disorder: an accelerated aging biomarker? The Journal of Affective Disorders 182, 64–69.CrossRefGoogle ScholarPubMed
Parajuli, B, Horiuchi, H, Mizuno, T, Takeuchi, H and Suzumura, A (2015) CCL11 enhances excitotoxic neuronal death by producing reactive oxygen species in microglia. Glia 63, 2274–2284.CrossRefGoogle ScholarPubMed
Qin, S, Rottman, JB, Myers, P, Kassam, N, Weinblatt, M, Loetscher, M, Koch, AE, Moser, B, Mackay, CR (1998) The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions. Journal of Clinical Investigation 101, 746.CrossRefGoogle ScholarPubMed
Rasmussen, HB, Timm, S, Wang, AG, Søeby, K, Lublin, H, Fenger, M, Hemmingsen, R, Werge, T (2006) Association between the CCR5 32-bp deletion allele and late onset of schizophrenia. The American Journal of Psychiatry 163, 507–511.CrossRefGoogle ScholarPubMed
Rowland, T, Perry, BI, Upthegrove, R, Barnes, N, Chatterjee, J, Gallacher, D, et al. (2018) Neurotrophins, cytokines, oxidative stress mediators and mood state in bipolar disorder: systematic review and meta-analyses. The British Journal of Psychiatry 213, 514–525.CrossRefGoogle Scholar
Sheehan, DV, Lecrubier, Y, Sheehan, KH, Amorim, P, Janavs, J, Weiller, E, Hergueta, T, Baker, R, 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. The Journal of Clinical Psychiatry 59 Suppl 20: 22–33;quiz 34–57.Google ScholarPubMed
Teixeira, AL, Reis, HJ, Nicolato, R, Brito-Melo, G, Correa, H, Teixeira, MM, Romano-Silva, MA (2008) Increased serum levels of CCL11/eotaxin in schizophrenia. Progress in Neuro-Psychopharmacology & Biological Psychiatry 32, 710–714.CrossRefGoogle Scholar
Tenscher, K, Metzner, B, Schopf, E, Norgauer, J and Czech, W (1996) Recombinant human eotaxin induces oxygen radical production, Ca (2+)-mobilization, actin reorganization, and CD11b upregulation in human eosinophils via a pertussis toxin-sensitive heterotrimeric guanine nucleotide-binding protein. Blood 88, 3195–3199.Google Scholar
Tokac, D, Tuzun, E, Gulec, H, Yılmaz, V, Bireller, ES, Cakmakoglu, B and Kucukali, CI (2016) Chemokine and chemokine receptor polymorphisms in bipolar disorder. Psychiatry Investigation 13, 541–548.CrossRefGoogle ScholarPubMed
Young, RC, Biggs, JT, Ziegler, VE and Meyer, DA (1978) A rating scale for mania: reliability, validity and sensitivity. The British Journal of Psychiatry 133, 429–435.CrossRefGoogle ScholarPubMed
Zlotnik, A and Yoshie, O (2000) Chemokines: a new classification system and their role in immunity. Immunity 12, 121–127.CrossRefGoogle ScholarPubMed