Hostname: page-component-78c5997874-xbtfd Total loading time: 0 Render date: 2024-11-15T07:26:39.819Z Has data issue: false hasContentIssue false

Association between childhood trauma exposure and pro-inflammatory cytokines in schizophrenia and bipolar-I disorder

Published online by Cambridge University Press:  18 December 2018

Yann Quidé*
Affiliation:
School of Psychiatry, University of New South Wales, Sydney, NSW, Australia Neuroscience Research Australia, Randwick, NSW, Australia
Chiara C. Bortolasci
Affiliation:
Centre for Molecular and Medical Research, School of Medicine, Deakin University, Geelong, VIC, Australia
Briana Spolding
Affiliation:
Centre for Molecular and Medical Research, School of Medicine, Deakin University, Geelong, VIC, Australia
Srisaiyini Kidnapillai
Affiliation:
Centre for Molecular and Medical Research, School of Medicine, Deakin University, Geelong, VIC, Australia
Oliver J. Watkeys
Affiliation:
School of Psychiatry, University of New South Wales, Sydney, NSW, Australia Neuroscience Research Australia, Randwick, NSW, Australia
Sarah Cohen-Woods
Affiliation:
School of Psychology, Flinders University, Adelaide, SA, Australia
Michael Berk
Affiliation:
Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia Florey Institute for Neuroscience and Mental Health, Parkville, VIC, Australia Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, VIC, Australia Deakin University, Impact Strategic Research Centre, Barwon Health, Geelong, VIC, Australia
Vaughan J. Carr
Affiliation:
School of Psychiatry, University of New South Wales, Sydney, NSW, Australia Neuroscience Research Australia, Randwick, NSW, Australia Department of Psychiatry, School of Clinical Sciences, Monash University, Clayton, VIC, Australia
Ken Walder
Affiliation:
Centre for Molecular and Medical Research, School of Medicine, Deakin University, Geelong, VIC, Australia
Melissa J. Green
Affiliation:
School of Psychiatry, University of New South Wales, Sydney, NSW, Australia Neuroscience Research Australia, Randwick, NSW, Australia
*
Author for correspondence: Dr Yann Quidé, E-mail: [email protected]; [email protected]

Abstract

Background

Elevated levels of pro-inflammatory cytokines are consistently reported in schizophrenia (SZ) and bipolar-I disorder (BD), as well as among individuals who have been exposed to childhood trauma. However, higher levels of inflammatory markers in these disorders are yet to be investigated with respect to levels of exposure to different types of childhood trauma.

Methods

Participants were 68 cases with a diagnosis of schizophrenia/schizoaffective disorder (SZ), 69 cases with a diagnosis of psychotic BD and 72 healthy controls (HC). Serum levels of interleukin 6 (IL-6), tumour necrosis factor-α (TNF-α) and C-reactive protein (CRP) were quantified, and childhood trauma exposure was assessed with the Childhood Trauma Questionnaire.

Results

The SZ group had significantly higher levels of IL-6, TNF-α and CRP when compared with the HC group (all p < 0.05, d = 0.41–0.63), as well as higher levels of TNF-α when compared with the BD group (p = 0.014, d = 0.50); there were no differences between the BD and HC groups for any markers. Exposure to sexual abuse was positively associated (standardised β = 0.326, t = 2.459, p = 0.018) with levels of CRP in the SZ group, but there were no significant associations between any form of trauma exposure and cytokine levels in the HC or BD groups.

Conclusions

These results contribute to the evidence for a chronic state of inflammation in SZ but not BD cases. Differential associations between trauma exposure and levels of pro-inflammatory cytokines across the diagnostic categories suggest that trauma may impact biological (stress and immune) systems differently in these patient groups.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aas, M, Dieset, I, Hope, S, Hoseth, E, Morch, 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, 342349.Google Scholar
Baumeister, D, Akhtar, R, Ciufolini, S, Pariante, CM and Mondelli, V (2016) Childhood trauma and adulthood inflammation: a meta-analysis of peripheral C-reactive protein, interleukin-6 and tumour necrosis factor-alpha. Molecular Psychiatry 21, 642649.Google Scholar
Benjamini, Y and Hochberg, Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. Journal of the Royal Statistical Society. Series B (Methodological) 57, 289300.Google Scholar
Bergink, V, Gibney, SM and Drexhage, HA (2014) Autoimmunity, inflammation, and psychosis: a search for peripheral markers. Biological Psychiatry 75, 324331.Google Scholar
Berk, M, Malhi, GS, Cahill, C, Carman, AC, Hadzi-Pavlovic, D, Hawkins, MT, Tohen, M and Mitchell, PB (2007) The Bipolar Depression Rating Scale (BDRS): its development, validation and utility. Bipolar Disorders 9, 571579.Google Scholar
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, 169190.Google Scholar
Beumer, W, Drexhage, RC, De Wit, H, Versnel, MA, Drexhage, HA and Cohen, D (2012) Increased level of serum cytokines, chemokines and adipokines in patients with schizophrenia is associated with disease and metabolic syndrome. Psychoneuroendocrinology 37, 19011911.Google Scholar
Cardno, AG, Rijsdijk, FV, Sham, PC, Murray, RM and McGuffin, P (2002) A twin study of genetic relationships between psychotic symptoms. American Journal of Psychiatry 159, 539545.Google Scholar
Castle, DJ, Jablensky, A, McGrath, JJ, Carr, V, Morgan, V, Waterreus, A, Valuri, G, Stain, H, McGuffin, P and Farmer, A (2006) The diagnostic interview for psychoses (DIP): development, reliability and applications. Psychological Medicine 36, 6980.Google Scholar
Chan, MK, Cooper, JD, Heilmann-Heimbach, S, Frank, J, Witt, SH, Nöthen, MM, Steiner, J, Rietschel, M and Bahn, S (2017) Associations between SNPs and immune-related circulating proteins in schizophrenia. Scientific Reports 7, 12586.Google Scholar
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, 180192.Google Scholar
Cutajar, MC, Mullen, PE, Ogloff, JR, Thomas, SD, Wells, DL and Spataro, J (2010) Schizophrenia and other psychotic disorders in a cohort of sexually abused children. Archives of General Psychiatry 67, 11141119.Google Scholar
Dargel, AA, Godin, O, Kapczinski, F, Kupfer, DJ and Leboyer, M (2015) C-reactive protein alterations in bipolar disorder: a meta-analysis. Journal of Clinical Psychiatry 76, 142150.Google Scholar
Davis, J, Maes, M, Andreazza, A, McGrath, JJ, Tye, SJ and Berk, M (2015) Towards a classification of biomarkers of neuropsychiatric disease: from encompass to compass. Molecular Psychiatry 20, 152153.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, 18651871.Google Scholar
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, 9095.Google Scholar
Dunn, AJ (2000) Cytokine activation of the HPA axis. Annals of the New York Academy of Sciences 917, 608617.Google Scholar
Fernandes, BS, Steiner, J, Bernstein, HG, Dodd, S, Pasco, JA, Dean, OM, Nardin, P, Goncalves, CA and Berk, M (2016 a) C-reactive protein is increased in schizophrenia but is not altered by antipsychotics: meta-analysis and implications. Molecular Psychiatry 21, 554564.Google Scholar
Fernandes, BS, Steiner, J, Molendijk, ML, Dodd, S, Nardin, P, Goncalves, CA, Jacka, F, Kohler, CA, Karmakar, C, Carvalho, AF and Berk, M (2016 b) C-reactive protein concentrations across the mood spectrum in bipolar disorder: a systematic review and meta-analysis. The Lancet. Psychiatry 3, 11471156.Google Scholar
Fisher, HL, Craig, TK, Fearon, P, Morgan, K, Dazzan, P, Lappin, J, Hutchinson, G, Doody, GA, Jones, PB, McGuffin, P, Murray, RM, Leff, J and Morgan, C (2011) Reliability and comparability of psychosis patients’ retrospective reports of childhood abuse. Schizophrenia Bulletin 37, 546553.Google Scholar
Girshkin, L, Matheson, SL, Shepherd, AM and Green, MJ (2014) Morning cortisol levels in schizophrenia and bipolar disorder: a meta-analysis. Psychoneuroendocrinology 49, 187206.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, 16961709.Google Scholar
Hepgul, N, Pariante, CM, Dipasquale, S, DiForti, M, Taylor, H, Marques, TR, Morgan, C, Dazzan, P, Murray, RM and Mondelli, V (2012) Childhood maltreatment is associated with increased body mass index and increased C-reactive protein levels in first-episode psychosis patients. Psychological Medicine 42, 18931901.Google Scholar
Kay, SR, Opler, LA and Lindenmayer, J-P (1989) The positive and negative syndrome scale (PANSS): rationale and standardisation. The British Journal of Psychiatry 155, 5965.Google Scholar
Kirkpatrick, B and Miller, BJ (2013) Inflammation and schizophrenia. Schizophrenia Bulletin 39, 11741179.Google Scholar
Leucht, S, Wahlbeck, K, Hamann, J and Kissling, W (2003) New generation antipsychotics versus low-potency conventional antipsychotics: a systematic review and meta-analysis. The Lancet 361, 15811589.Google Scholar
Liu, J, Chen, J, Ehrlich, S, Walton, E, White, T, Perrone-Bizzozero, N, Bustillo, J, Turner, JA and Calhoun, VD (2014) Methylation patterns in whole blood correlate with symptoms in schizophrenia patients. Schizophrenia Bulletin 40, 769776.Google Scholar
Loughland, C, Draganic, D, McCabe, K, Richards, J, Nasir, A, Allen, J, Catts, S, Jablensky, A, Henskens, F, Michie, P, Mowry, B, Pantelis, C, Schall, U, Scott, R, Tooney, P and Carr, V (2010) Australian schizophrenia Research Bank: a database of comprehensive clinical, endophenotypic and genetic data for aetiological studies of schizophrenia. Australian and New Zealand Journal of Psychiatry 44, 10291035.Google Scholar
Lovibond, SH and Lovibond, PF (1995) The DASS: Manual for the Depression, Anxiety Stress Scales, 2nd Edn. Sydney, NSW, Australia: Psychology Foundation of Australia.Google Scholar
Matheson, SL, Shepherd, AM, Pinchbeck, RM, Laurens, KR and Carr, VJ (2013) Childhood adversity in schizophrenia: a systematic meta-analysis. Psychological Medicine 43, 225238.Google Scholar
McGrath, JJ, Saha, S, Lim, CCW, Aguilar-Gaxiola, S, Alonso, J, Andrade, LH, Bromet, EJ, Bruffaerts, R, Caldas de Almeida, JM, Cardoso, G, de Girolamo, G, Fayyad, J, Florescu, S, Gureje, O, Haro, JM, Kawakami, N, Koenen, KC, Kovess-Masfety, V, Lee, S, Lepine, JP, McLaughlin, KA, Medina-Mora, ME, Navarro-Mateu, F, Ojagbemi, A, Posada-Villa, J, Sampson, N, Scott, KM, Tachimori, H, Ten Have, M, Kendler, KS, Kessler, RC and Collaborators, W. H. O. W. M. H. S. (2017) Trauma and psychotic experiences: transnational data from the World Mental Health Survey. The British Journal of Psychiatry 211, 373380.Google Scholar
McGuffin, P and Farmer, A (1991) A polydiagnostic application of operational criteria in studies of psychotic illness: development and validation of the OPCRIT system. Archives of General Psychiatry 48, 764770.Google Scholar
Miller, BJ, Buckley, P, Seabolt, W, Mellor, A and Kirkpatrick, B (2011) Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biological Psychiatry 70, 663671.Google Scholar
Miller, BJ, Culpepper, N and Rapaport, MH (2014) C-reactive protein levels in schizophrenia: a review and meta-analysis. Clinical Schizophrenia and Related Psychoses 7, 223230.Google Scholar
Mitchell, PB, Johnston, AK, Corry, J, Ball, JR and Malhi, GS (2009) Characteristics of bipolar disorder in an Australian specialist outpatient clinic: comparison across large datasets. Australian and New Zealand Journal of Psychiatry 43, 10091017.Google Scholar
Modabbernia, A, Taslimi, S, Brietzke, E and Ashrafi, M (2013) Cytokine alterations in bipolar disorder: a meta-analysis of 30 studies. Biological Psychiatry 74, 1525.Google Scholar
Montgomery, P and Asberg, B (1979) A new depression scale designed to be sensitive to change. The British Journal of Psychiatry 134, 382389.Google Scholar
Moraes, JB, Maes, M, Barbosa, DS, Ferrari, TZ, Uehara, MKS, Carvalho, AF and Nunes, SOV (2017) Elevated C-reactive protein levels in women with bipolar disorder may be explained by a history of childhood trauma, especially sexual abuse, body mass Index and Age. CNS Neurological Disorders – Drug Targets 16, 514521.Google Scholar
Morris, G and Berk, M (2015) The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders. BMC Medicine 13, 68.Google Scholar
Munkholm, K, Brauner, JV, Kessing, LV and Vinberg, M (2013) Cytokines in bipolar disorder vs. healthy control subjects: a systematic review and meta-analysis. Journal of Psychiatric Research 47, 11191133.Google Scholar
Potvin, S, Stip, E, Sepehry, AA, Gendron, A, Bah, R and Kouassi, E (2008) Inflammatory cytokine alterations in schizophrenia: a systematic quantitative review. Biological Psychiatry 63, 801808.Google Scholar
Rodrigues-Amorim, D, Rivera-Baltanas, T, Spuch, C, Caruncho, HJ, Gonzalez-Fernandez, A, Olivares, JM and Agis-Balboa, RC (2017) Cytokines dysregulation in schizophrenia: a systematic review of psychoneuroimmune relationship. Schizophrenia Research 197, 1933.Google Scholar
Schizophrenia Working Group of the Psychiatric Genomics, C. (2014) Biological insights from 108 schizophrenia-associated genetic loci. Nature 511, 421427.Google Scholar
Sheehan, DV, Lecrubier, Y, Sheehan, KH, Amorim, P, Janvas, J, Weiller, E, Hergueta, T, Baker, R and Dunbar, GC (1998) The mini-international neuropsychiatric interview (MINI): the development and validation of a structured diagnostic interview for DSM-IV and ICD-10. Journal of Clinical Psychiatry 59, 2233.Google Scholar
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, 661671.Google Scholar
W.H.O. (2008) ICD-10: International Statistical Classification of Diseases and Related Health Problems , 10th Rev. ed.. New York: World Health Organization.Google Scholar
Wechsler, D (1999) Wechsler Abbreviated Scale of Intelligence (WASI). New York: The Psychological Corporation.Google Scholar
Woods, SW (2003) Chlorpromazine equivalent doses for the newer atypical antipsychotics. Journal of Clinical Psychiatry 64, 663667.Google Scholar
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, 429435.Google Scholar