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Cytokine profile in first-episode psychosis, unaffected siblings and community-based controls: the effects of familial liability and childhood maltreatment

Published online by Cambridge University Press:  08 May 2019

Fabiana Corsi-Zuelli Open the ORCID record for Fabiana Corsi-Zuelli [Opens in a new window] ,
Camila Marcelino Loureiro ,
Rosana Shuhama ,
Helene Aparecida Fachim ,
Paulo Rossi Menezes ,
Paulo Louzada-Junior ,
Valeria Mondelli  and
Cristina Marta Del-Ben
Fabiana Corsi-Zuelli*
Affiliation:
Department of Neuroscience and Behaviour, Division of Psychiatry, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
Camila Marcelino Loureiro
Affiliation:
Department of Internal Medicine, Division of Clinical Immunology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
Rosana Shuhama
Affiliation:
Department of Neuroscience and Behaviour, Division of Psychiatry, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
Helene Aparecida Fachim
Affiliation:
Department of Neuroscience and Behaviour, Division of Psychiatry, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil Biomolecular Sciences Research Centre, Sheffield Hallam University, Sheffield, UK
Paulo Rossi Menezes
Affiliation:
Department of Preventive Medicine, Faculty of Medicine, University of São Paulo, São Paulo, Brazil
Paulo Louzada-Junior
Affiliation:
Department of Internal Medicine, Division of Clinical Immunology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
Valeria Mondelli
Affiliation:
Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
Cristina Marta Del-Ben
Affiliation:
Department of Neuroscience and Behaviour, Division of Psychiatry, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
*
Author for correspondence: Fabiana Corsi-Zuelli, E-mail: [email protected]; [email protected]
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Abstract

Background

Inflammation is a possible biological mechanism underlying the association between childhood maltreatment and psychosis. Previous investigations on this regard were mainly conducted on chronic schizophrenia and lacked control for confounders. We aim to investigate the role of familial liability, childhood maltreatment and recent stress in determining cytokine abnormalities at the onset of psychosis.

Methods

We recruited 114 first-episode psychosis (FEP) patients, 57 unaffected biological siblings of FEP patients, and 251 community-based controls. Plasma cytokines (IL-1β, IL-6, TNF-α, IFN-γ, IL-4, IL-10 and TGF-β) were measured and differences across the groups analysed after adjusting for potential confounders.

Results

FEP had a higher pro- and anti-inflammatory cytokine profile (IL-1β, IL-6, TNF-α, IL-10 and TGF-β), which was not observed in unaffected siblings. Siblings presented decreased IL-1β when compared with patients and controls. Childhood maltreatment was associated with higher levels of TGF-β in both patients and siblings when compared with controls. Physical childhood abuse was associated with increased levels of TGF-β in FEP patients but with decreased levels in controls. Other childhood maltreatment subtypes or recent stressors did not affect cytokine levels in any of the groups.

Conclusions

Normal or reduced cytokines in siblings represent possibly a protective factor and suggest that the identified inflammatory profile in FEP can be a real pathophysiological component of psychosis. Experience of childhood maltreatment may contribute as long-term immune priming for the TGF-β pathway, and increased levels of this cytokine in both patients and siblings exposed to childhood maltreatment point to a possible biological candidate of familial risk for psychosis.

Keywords

Anti-inflammatory cytokineschildhood maltreatmentcytokinesearly-life stressfirst-episode psychosisinflammationpro-inflammatory cytokinesschizophreniasiblingstransforming growth factor-beta
Type
Original Articles
Information
Psychological Medicine , Volume 50 , Issue 7 , May 2020 , pp. 1139 - 1147
Copyright
Copyright © Cambridge University Press 2019

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References

Aas, M, Dieset, I, Hope, S, Hoseth, E, Mørch, R, Reponen, E, Steen, NE, Laskemoen, JF, Ueland, T, Aukrust, P, Agartz, I, Andreassen, OA and Melle, I (2017) Childhood maltreatment severity is associated with elevated C-reactive protein and body mass index in adults with schizophrenia and bipolar diagnoses. Brain, Behavior, and Immunity 65, 342–349.CrossRefGoogle ScholarPubMed
Amoli, MM, Khatami, F, Arzaghi, SM, Enayati, S and Nejatisafa, A-A (2019) Over-expression of TGF-β1 gene in medication free Schizophrenia. Psychoneuroendocrinology 99, 265–270.CrossRefGoogle ScholarPubMed
Archer, JA, Hutchison, IL, Dorudi, S, Stansfeld, SA and Korszun, A (2012) Interrelationship of depression, stress and inflammation in cancer patients: a preliminary study. Journal of Affective Disorders 143, 39–46.CrossRefGoogle ScholarPubMed
Baumeister, D, Akhtar, R, Ciufolini, S, Pariante, CM and Mondelli, V (2015) Childhood trauma and adulthood inflammation: a meta-analysis of peripheral C-reactive protein, interleukin-6 and tumour necrosis factor-α. Molecular Psychiatry 21, 642–649.CrossRefGoogle ScholarPubMed
Baumeister, D, Ciufolini, S and Mondelli, V (2016) Effects of psychotropic drugs on inflammation: consequence or mediator of therapeutic effects in psychiatric treatment? Psychopharmacology 233, 1575–1589.CrossRefGoogle ScholarPubMed
Bernstein, DP, Stein, JA, Newcomb, MD, Walker, E, Pogge, D, Ahluvalia, T, Stokes, J, Handelsman, L, Medrano, M, Desmond, D and Zule, W (2003) Development and validation of a brief screening version of the Childhood Trauma Questionnaire. Child Abuse and Neglect 27, 169–190.CrossRefGoogle ScholarPubMed
Borovcanin, M, Jovanovic, I, Radosavljevic, G, Djukic Dejanovic, S, Stefanovic, V, Arsenijevic, N and Lukic, ML (2013) Antipsychotics can modulate the cytokine profile in schizophrenia: attenuation of the type-2 inflammatory response. Schizophrenia Research 147, 103–109.CrossRefGoogle ScholarPubMed
Brugha, T, Bebbington, P, Tennant, C and Hurry, J (1985) The list of threatening experiences: a subset of 12 life event categories with considerable long-term contextual threat. Psychological Medicine 15, 189–194.CrossRefGoogle ScholarPubMed
Calevro, A, Cotel, M-C, Natesan, S, Modo, M, Vernon, AC and Mondelli, V (2018) Effects of chronic antipsychotic drug exposure on the expression of Translocator Protein and inflammatory markers in rat adipose tissue. Psychoneuroendocrinology 95, 28–33.CrossRefGoogle ScholarPubMed
Chen, W, Jin, W, Hardegen, N, Lei, K, Li, L, Marinos, N, McGrady, G and Wahl, SM (2003) Conversion of Peripheral CD4+ CD25− Naive T Cells to CD4+ CD25+ Regulatory T Cells by TGF-β induction of Transcription Factor Foxp3. The Journal of Experimental Medicine 198, 1875–1886.CrossRefGoogle ScholarPubMed
Coelho, R, Viola, TW, Walss-Bass, C, Brietzke, E and Grassi-Oliveira, R (2014) Childhood maltreatment and inflammatory markers: a systematic review. Acta Psychiatrica Scandinavica 129, 180–192.CrossRefGoogle ScholarPubMed
Crippa, JA, Sanches, RF, Hallak, JE, Loureiro, SR and Zuardi, AW (2001) A structured interview guide increases Brief Psychiatric Rating Scale reliability in raters with low clinical experience. Acta Psychiatrica Scandinavica 103, 465–470.CrossRefGoogle ScholarPubMed
Del-Ben, CM, Vilela, JAA, de Crippa, JAS, Hallak, JEC, Labate, CM and Zuardi, AW (2001) Confiabilidade da ‘Entrevista Clínica Estruturada para o DSM-IV – Versão Clínica’ traduzida para o português. Revista Brasileira de Psiquiatria 23, 156–159.CrossRefGoogle Scholar
Del-Ben, CM, Shuhama, R, Loureiro, CM, Ragazzi, TCC, Zanatta, DP, Tenan, SHG, Santos, JLF, Louzada-Junior, P, Santos, AC, Morgan, C, Menezes, PR. Urbanicity and risk of first episode psychosis: an incidence study in Brazil. British Journal of Psychiatry (accepted).Google Scholar
Dennison, U, McKernan, D, Cryan, J and Dinan, T (2012) Schizophrenia patients with a history of childhood trauma have a pro-inflammatory phenotype. Psychological Medicine 42, 1865–1871.CrossRefGoogle ScholarPubMed
Di Forti, M, Morgan, C, Dazzan, P, Pariante, C, Mondelli, V, Marques, TR, Handley, R, Luzi, S, Russo, M, Paparelli, A, Butt, A, Stilo, SA, Wiffen, B, Powell, J and Murray, RM (2009) High-potency cannabis and the risk of psychosis. British Journal of Psychiatry 195, 488–491.CrossRefGoogle ScholarPubMed
Di Nicola, M, Cattaneo, A, Hepgul, N, Di Forti, M, Aitchison, KJ, Janiri, L, Murray, RM, Dazzan, P, Pariante, CM and Mondelli, V (2013) Serum and gene expression profile of cytokines in first-episode psychosis. Brain, Behavior, and Immunity 31, 90–95.CrossRefGoogle ScholarPubMed
Drexhage, RC, Hoogenboezem, TA, Cohen, D, Versnel, MA, Nolen, WA, van Beveren, NJM and Drexhage, HA (2011). An activated set point of T-cell and monocyte inflammatory networks in recent-onset schizophrenia patients involves both pro- and anti-inflammatory forces. The International Journal of Neuropsychopharmacology 14, 746–755.CrossRefGoogle ScholarPubMed
First, MB, Spitzer, RL, Gibbon, M and Williams, JBW (1997) Structured clinical interview for DSM-IV axis I disorders SCID-I: clinician version, administration booklet. American Psychiatric Publishing.Google Scholar
Goldsmith, DR, Rapaport, MH and Miller, BJ (2016) A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression. Molecular Psychiatry 21, 1696–1709.CrossRefGoogle ScholarPubMed
Grassi-Oliveira, R, Stein, LM and Pezzi, JC (2006) Tradução e validação de conteúdo da versão em português do Childhood Trauma Questionnaire. Revista de Saude Publica 40, 249–255.CrossRefGoogle Scholar
Grosse, L, Ambrée, O, Jörgens, S, Jawahar, MC, Singhal, G, Stacey, D, Arolt, V and Baune, BT (2016) Cytokine levels in major depression are related to childhood trauma but not to recent stressors. Psychoneuroendocrinology 73, 24–31.CrossRefGoogle ScholarPubMed
ISPCAN, International Society for the Prevention of Child Abuse and Neglect (2014) World Perspectives on Child Abuse. Australian Institute of Criminology, Oak Foundation (11th ed.)Google Scholar
Jia, P, Wang, L, Meltzer, HY and Zhao, Z (2010) Common variants conferring risk of schizophrenia: a pathway analysis of GWAS data. Schizophrenia Research 122, 38–42.CrossRefGoogle ScholarPubMed
Jongsma, HE, Gayer-Anderson, C, Lasalvia, A, Quattrone, D, Mulè, A, Szöke, A, Selten, J-P, Turner, C, Arango, C, Tarricone, I, Berardi, D, Tortelli, A, Llorca, P-M, de Haan, L, Bobes, J, Bernardo, M, Sanjuán, J, Santos, JL, Arrojo, M, Del-Ben, CM, Menezes, PR, Velthorst, E, Murray, RM, Rutten, BP, Jones, PB, van Os, J, Morgan, C and Kirkbride, JB (2018) Treated incidence of psychotic disorders in the multinational EU-GEI Study. JAMA Psychiatry 75, 36.CrossRefGoogle ScholarPubMed
Khandaker, GM, Pearson, RM, Zammit, S, Lewis, G and Jones, PB (2014) Association of serum interleukin 6 and C-reactive protein in childhood with depression and psychosis in young adult life. JAMA Psychiatry 71, 1121–1128.CrossRefGoogle ScholarPubMed
Kim, YK, Myint, AM, Lee, BH, Han, CS, Lee, HJ, Kim, DJ and Leonard, BE (2004) Th1, Th2 and Th3 cytokine alteration in schizophrenia. Progress in Neuro-Psychopharmacology and Biological Psychiatry 28, 1129–1134.CrossRefGoogle Scholar
Loureiro, CM, Shuhama, R, Fachim, HA, Menezes, PR, Del-Ben, CM and Louzada-Junior, P (2018) Low plasma concentrations of N-methyl-d-aspartate receptor subunits as a possible biomarker for psychosis. Schizophrenia Research 202, 55–63.CrossRefGoogle Scholar
McGrath, JJ, McLaughlin, KA, Saha, S, Aguilar-Gaxiola, S, Al-Hamzawi, A, Alonso, J, Bruffaerts, R, De Girolamo, G, De Jonge, P, Esan, O, Florescu, S, Gureje, O, Haro, JM, Hu, C, Karam, EG, Kovess-Masfety, V, Lee, S, Lepine, JP, Lim, CCW, Medina-Mora, ME, Mneimneh, Z, Pennell, BE, Piazza, M, Posada-Villa, J, Sampson, N, Viana, MC, Xavier, M, Bromet, EJ, Kendler, KS and Kessler, RC (2017) The association between childhood adversities and subsequent first onset of psychotic experiences: a cross-national analysis of 23 998 respondents from 17 countries. Psychological Medicine 47, 1230–1245.CrossRefGoogle ScholarPubMed
Metcalf, SA, Jones, PB, Nordstrom, T, Timonen, M, Mäki, P, Miettunen, J, Jääskeläinen, E, Järvelin, M-R, Stochl, J, Murray, GK, Veijola, J and Khandaker, GM (2017) Serum C-reactive protein in adolescence and risk of schizophrenia in adulthood: a prospective birth cohort study. Brain, Behavior, and Immunity 59, 253–259.CrossRefGoogle ScholarPubMed
Numata, S, Ueno, S, Iga, J, Yamauchi, K, Hongwei, S, Hashimoto, R, Takeda, M, Kunugi, H, Itakura, M and Ohmori, T (2008) TGFBR2 gene expression and genetic association with schizophrenia. Journal of Psychiatric Research 42, 425–432.CrossRefGoogle ScholarPubMed
Overall, JE and Gorham, DR (1962) The brief psychiatric rating scale. Psychological Reports 10, 799–812.CrossRefGoogle Scholar
Pillinger, T, Osimo, EF, Brugger, S, Mondelli, V, McCutcheon, RA and Howes, OD (2018) A meta-analysis of immune parameters, variability, and assessment of modal distribution in psychosis and test of the immune subgroup hypothesis. Schizophrenia Bulletin.Google Scholar
Quidé, Y, Bortolasci, CC, Spolding, B, Kidnapillai, S, Watkeys, OJ, Cohen-Woods, S, Berk, M, Carr, VJ, Walder, K and Green, MJ (2018) Association between childhood trauma exposure and pro-inflammatory cytokines in schizophrenia and bipolar-I disorder. Psychological Medicine 1–9.Google ScholarPubMed
Rates, SMM, Melo, EM de Mascarenhas, MDM and Malta, DC (2015) Violence against children: an analysis of mandatory reporting of violence, Brazil 2011. FapUNIFESP (SciELO). Ciência & Saúde Coletiva 20, 655–665.CrossRefGoogle Scholar
Ripke, S, Neale, BM, Corvin, A, Walters, JT, Farh, KH, Holmans, PA, Lee, P, Bulik-Sullivan, B, Collier, DA, Huang, H, Pers, TH, Agartz, I, Agerbo, E, Albus, M, Alexander, M, Amin, F, Bacanu, SA, Begemann, M, Belliveau, RA Jr, Bene, J, Bergen, SE, Bevilacqua, E, Bigdeli, TB, Black, DW, Bruggeman, R, Buccola, NG, Buckner, RL, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Catts, SV, Chambert, KD, Chan, RC, Chen, RY, Chen, EY, Cheng, W, Cheung, EF, Chong, SA, Cloninger, CR, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crowley, JJ, Curtis, D, Davidson, M, Davis, KL, Degenhardt, F, Del Favero, J, Demontis, D, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott-Price, V, Essioux, L, Fanous, AH, Farrell, MS, Frank, J, Franke, L, Freedman, R, Freimer, NB, Friedl, M, Friedman, JI, Fromer, M, Genovese, G, Georgieva, L, Giegling, I, Giusti-Rodríguez, P, Godard, S, Goldstein, JI, Golimbet, V, Gopal, S, Gratten, J, de Haan, L, Hammer, C, Hamshere, ML, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, AM, Henskens, FA, Herms, S, Hirschhorn, JN, Hoffmann, P, Hofman, A, Hollegaard, MV, Hougaard, DM, Ikeda, M, Joa, I, Julià, A, Kahn, RS, Kalaydjieva, L, Karachanak-Yankova, S, Karjalainen, J, Kavanagh, D, Keller, MC, Kennedy, JL, Khrunin, A, Kim, Y, Klovins, J, Knowles, JA, Konte, B, Kucinskas, V, Ausrele Kucinskiene, Z, Kuzelova-Ptackova, H, Kähler, AK, Laurent, C, Keong, JL, Lee, SH, Legge, SE, Lerer, B, Li, M, Li, T, Liang, KY, Lieberman, J, Limborska, S, Loughland, CM, Lubinski, J, Lönnqvist, J, Macek, M Jr, Magnusson, PK, Maher, BS, Maier, W, Mallet, J, Marsal, S, Mattheisen, M, Mattingsdal, M, McCarley, RW, McDonald, C, McIntosh, AM, Meier, S, Meijer, CJ, Melegh, B, Melle, I, Mesholam-Gately, RI, Metspalu, A, Michie, PT, Milani, L, Milanova, V, Mokrab, Y, Morris, DW, Mors, O, Murphy, KC, Murray, RM, Myin-Germeys, I, Müller-Myhsok, B, Nelis, M, Nenadic, I, Nertney, DA, Nestadt, G, Nicodemus, KK, Nikitina-Zake, L, Nisenbaum, L, Nordin, A, O'Callaghan, E, O'Dushlaine, C, O'Neill, FA, Oh, SY, Olincy, A, Olsen, L, Van Os, J, Pantelis, C, Papadimitriou, GN, Papiol, S, Parkhomenko, E, Pato, MT, Paunio, T, Pejovic-Milovancevic, M, Perkins, DO, Pietiläinen, O, Pimm, J, Pocklington, AJ, Powell, J, Price, A, Pulver, AE, Purcell, SM, Quested, D, Rasmussen, HB, Reichenberg, A, Reimers, MA, Richards, AL, Roffman, JL, Roussos, P, Ruderfer, DM, Salomaa, V, Sanders, AR, Schall, U, Schubert, CR, Schulze, TG, Schwab, SG, Scolnick, EM, Scott, RJ, Seidman, LJ, Shi, J, Sigurdsson, E, Silagadze, T, Silverman, JM, Sim, K, Slominsky, P, Smoller, JW, So, HC, Spencer, CA, Stahl, EA, Stefansson, H, Steinberg, S, Stogmann, E, Straub, RE, Strengman, E, Strohmaier, J, Stroup, TS, Subramaniam, M, Suvisaari, J, Svrakic, DM, Szatkiewicz, JP, Söderman, E, Thirumalai, S, Toncheva, D, Tosato, S, Veijola, J, Waddington, J, Walsh, D, Wang, D, Wang, Q, Webb, BT, Weiser, M, Wildenauer, DB, Williams, NM, Williams, S, Witt, SH, Wolen, AR, Wong, EH, Wormley, BK, Xi, HS, Zai, CC, Zheng, X, Zimprich, F, Wray, NR, Stefansson, K, Visscher, PM, Adolfsson, R, Andreassen, OA, Blackwood, DH, Bramon, E, Buxbaum, JD, Børglum, AD, Cichon, S, Darvasi, A, Domenici, E, Ehrenreich, H, Esko, T, Gejman, PV, Gill, M, Gurling, H, Hultman, CM, Iwata, N, Jablensky, AV, Jönsson, EG, Kendler, KS, Kirov, G, Knight, J, Lencz, T, Levinson, DF, Li, QS, Liu, J, Malhotra, AK, McCarroll, SA, McQuillin, A, Moran, JL, Mortensen, PB, Mowry, BJ, Nöthen, MM, Ophoff, RA, Owen, MJ, Palotie, A, Pato, CN, Petryshen, TL, Posthuma, D, Rietschel, M, Riley, BP, Rujescu, D, Sham, PC, Sklar, P, St Clair, D, Weinberger, DR, Wendland, JR, Werge, T, Daly, MJ, Sullivan, PF and O'Donovan, MC (2014) Biological insights from 108 schizophrenia-associated genetic loci. Nature 511, 421–427.Google Scholar
Rohleder, N (2014) Stimulation of systemic low-grade inflammation by psychosocial stress. Psychosomatic Medicine 76, 181–189.CrossRefGoogle ScholarPubMed
Sanders, AR, Drigalenko, EI, Duan, J, Moy, W, Freda, J, Göring, HHH, Gejman, PV, Levinson, DF, Shi, J, Buccola, NG, Mowry, BJ, Freedman, R, Olincy, A, Amin, F, Black, DW, Silverman, JM, Byerley, WF, Cloninger, CR and Svrakic, DM (2017) Transcriptome sequencing study implicates immune-related genes differentially expressed in schizophrenia: new data and a meta-analysis. Translational Psychiatry 7, 1–10.CrossRefGoogle ScholarPubMed
Singh, SP, Cooper, JE, Fisher, HL, Tarrant, CJ, Lloyd, T, Banjo, J, Corfe, S and Jones, P (2005) Determining the chronology and components of psychosis onset: the Nottingham Onset Schedule (NOS). Schizophrenia Research 80, 117–130.CrossRefGoogle Scholar
Sun, M, Gewirtz, JC, Bofenkamp, L, Wickham, RJ, Ge, H and O'Connor, MB (2010) Canonical TGF- signaling is required for the balance of excitatory/inhibitory transmission within the hippocampus and prepulse inhibition of acoustic startle. Journal of Neuroscience 30, 6025–6035.CrossRefGoogle ScholarPubMed
Varese, F, Smeets, F, Drukker, M, Lieverse, R, Lataster, T, Viechtbauer, W, Read, J, Van Os, J and Bentall, RP (2012) Childhood adversities increase the risk of psychosis: a meta-analysis of patient-control, prospective- and cross-sectional cohort studies. Schizophrenia Bulletin 38, 661–671.CrossRefGoogle ScholarPubMed