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Schizophrenia patients with a history of childhood trauma have a pro-inflammatory phenotype

Published online by Cambridge University Press:  23 February 2012

U. Dennison*
Department of Psychiatry, University College Cork, Cork, Ireland
D. McKernan
Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland
J. Cryan
Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland Department of Anatomy, University College Cork, Cork, Ireland
T. Dinan
Department of Psychiatry, University College Cork, Cork, Ireland Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland
*Address for correspondence: Dr U. Dennison, c/o City General Hospital, Infirmary Road, Cork, Ireland. (Email:



Increasing evidence indicates that childhood trauma is a risk factor for schizophrenia and patients with this syndrome have a pro-inflammatory phenotype. We tested the hypothesis that the pro-inflammatory phenotype in schizophrenia is associated with childhood trauma and that patients without a history of such trauma have a similar immune profile to healthy controls.


We recruited 40 schizophrenia patients and 40 controls, all of whom completed the Childhood Trauma Questionnaire (CTQ). Using enzyme-linked immunosorbent assay (ELISA) techniques, we measured peripheral levels of interleukin (IL)-1β, IL-6, IL-8 and tumour necrosis factor (TNF)-α. These immune parameters were compared in schizophrenia with childhood trauma, schizophrenia without childhood trauma and healthy controls.


Patients with childhood trauma had higher levels of IL-6 and TNF-α than patients without trauma and healthy controls, and TNF-α levels correlated with the extent of the trauma. Patients with no trauma had similar immune profiles to controls.


Childhood trauma drives changes, possibly epigenetic, that generate a pro-inflammatory phenotype.

Original Articles
Copyright © Cambridge University Press 2012

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Addington, D, Addington, J, Maticka-Tyndale, E (1993). Assessing depression in schizophrenia: the Calgary Depression Scale. British Journal of Psychiatry. Supplement 3944.CrossRefGoogle ScholarPubMed
Addington, D, Addington, J, Maticka-Tyndale, E, Joyce, J (1992). Reliability and validity of a depression rating scale for schizophrenics. Schizophrenia Research 6, 201208.Google Scholar
APA (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th edn. American Psychiatric Association: Washington, DC.Google Scholar
Bernstein, D, Fink, L, Handelsman, L, Foote, J, Lovejoy, M, Wenzel, K, Sapareto, E, Ruggiero, J (1994). Initial reliability and validity of a new retrospective measure of child abuse and neglect. American Journal of Psychiatry 151, 11321136.Google Scholar
Boynton-Jarrett, R, Fargnoli, J, Suglia, SF, Zuckerman, B, Wright, RJ (2010). Association between maternal intimate partner violence and incident obesity in preschool-aged children: results from the Fragile Families and Child Well-being Study. Archives of Paediatric and Adolescent Medicine 164, 540546.CrossRefGoogle ScholarPubMed
Braehler, C, Holowka, D, Brunet, A, Beaulieu, S, Baptista, T, Debruille, JB, Walker, CD, King, S (2005). Diurnal cortisol in schizophrenia patients with childhood trauma. Schizophrenia Research 79, 353354.Google Scholar
Bremner, JD (2005). Effects of traumatic stress on brain structure and function: relevance to early responses to trauma. Journal of Trauma and Dissociation 6, 5168.CrossRefGoogle ScholarPubMed
Brown, AS (2011). The environment and susceptibility to schizophrenia. Progress in Neurobiology 93, 2358.Google Scholar
Brydon, L, Wright, CE, O'Donnell, K, Zachary, I, Wardle, J, Steptoe, A (2008). Stress-induced cytokine responses and central adiposity in young women. International Journal of Obesity 32, 443450.CrossRefGoogle ScholarPubMed
Carpenter, LL, Gawuga, CE, Tyrka, AR, Lee, JK, Anderson, GM, Price, LH (2010). Association between plasma IL-6 response to acute stress and early-life adversity in healthy adults. Neuropsychopharmacology 35, 26172623.Google Scholar
Carpenter, LL, Tyrka, AR, Ross, NS, Khoury, L, Anderson, GM, Price, LH (2009). Effect of childhood emotional abuse and age on cortisol responsivity in adulthood. Biological Psychiatry 66, 6975.Google Scholar
Cicchetti, D, Walker, EF (2001). Stress and development: biological and psychological consequences. Development and Psychopathology 13, 413418.CrossRefGoogle Scholar
Commins, SP, Borish, L, Steinke, JW (2010). Immunologic messenger molecules: cytokines, interferons, and chemokines. Journal of Allergy and Clinical Immunology 125, S53S72.CrossRefGoogle ScholarPubMed
Danese, A, Moffitt, TE, Pariante, CM, Ambler, A, Poulton, R, Caspi, A (2008). Elevated inflammation levels in depressed adults with a history of childhood maltreatment. Archives of General Psychiatry 65, 409415.Google Scholar
Dantzer, R, O'Connor, JC, Freund, GG, Johnson, RW, Kelley, KW (2008). From inflammation to sickness and depression: when the immune system subjugates the brain. Nature Reviews Neuroscience 9, 4656.Google Scholar
Frank, M, Baratta, M, Sprunger, D, Watkins, L, Maier, S (2007). Microglia serve as a neuroimmune substrate for stress induced potentiation of CNS pro-inflammatory cytokine responses. Brain, Behavior and Immunity 21, 4759.CrossRefGoogle ScholarPubMed
Galletly, C, van Hooff, M, McFarlane, A (2011). Psychotic symptoms in young adults exposed to childhood trauma – a 20 year follow-up study. Schizophrenia Research 127, 7682.Google Scholar
Hall, F, Wilkinson, L, Humby, T, Robbins, T (1999). Maternal deprivation of neonatal rats produces enduring changes in dopamine function. Synapse 32, 3743.3.0.CO;2-4>CrossRefGoogle ScholarPubMed
Hardt, J, Rutter, M (2004). Validity of adult retrospective reports of adverse childhood experiences: review of the evidence. Journal of Child Psychology and Psychiatry 45, 260273.CrossRefGoogle ScholarPubMed
Heim, C, Mletzko, T, Purselle, D, Musselman, DL, Nemeroff, CB (2008 a). The dexamethasone/corticotropin-releasing factor test in men with major depression: role of childhood trauma. Biological Psychiatry 63, 398405.Google Scholar
Heim, C, Newport, DJ, Mletzko, T, Miller, AH, Nemeroff, CB (2008 b). The link between childhood trauma and depression: insights from HPA axis studies in humans. Psychoneuroendocrinology 33, 693710.CrossRefGoogle ScholarPubMed
Janssen, I, Krabbendam, L, Bak, M, Hanssen, M, Volleberg, W, de Graaf, R, van Os, J (2004). Childhood abuse as a risk factor for psychotic experiences. Acta Psychiatrica Scandinavica 109, 3845.CrossRefGoogle ScholarPubMed
Kay, S, Fiszbein, A, Opler, L (1987). The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261276.Google Scholar
Kvasnicka, T, Kvasnicka, J, Ceska, R, Vrablik, M (2003). Increase of inflammatory state in overweight adults with combined hyperlipidemia. Nutrition, Metabolism and Cardiovascular Diseases 13, 227231.Google Scholar
LeMay, LG, Vander, AJ, Kluger, MJ (1990). The effects of psychological stress on plasma interleukin-6 activity in rats. Physiology and Behavior 47, 957961.CrossRefGoogle ScholarPubMed
Leonard, BE, Myint, A (2009). The psychoneuroimmunology of depression. Human Psychopharmacology 24, 165175.Google Scholar
Leucht, S, Kane, JM, Kissling, W, Hamann, J, Etschel, E, Engel, RR (2005). What does the PANSS mean? Schizophrenia Research 79, 231238.CrossRefGoogle ScholarPubMed
Liu, D, Diorio, J, Tannenbaum, B, Caldji, C, Francis, D, Freedman, A, Sharma, S, Pearson, D, Plotsky, PM, Meaney, MJ (1997). Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. Science 277, 16591662.Google Scholar
Maes, M, Delange, J, Ranjan, R, Meltzer, HY, Desnyder, R, Cooremans, W, Scharpe, S (1997). Acute phase proteins in schizophrenia, mania and major depression: modulation by psychotropic drugs. Psychiatry Research 66, 111.CrossRefGoogle ScholarPubMed
Mondelli, V, Cattaneo, A, Belvederi Murri, M, Di Forti, M, Handley, R, Hepgul, N, Miorelli, A, Navari, S, Papadopoulos, A, Aitchinson, K, Morgan, C, Murray, R, Dazzan, P, Pariante, C (2011). Stress and inflammation reduce brain-derived neurotrophic factor expression in first-episode psychosis: a pathway to smaller hippocampal volumes. Journal of Clinical Psychiatry. Published online: 18 May 2011. doi:10.4088/JCP.10m06745.Google Scholar
Mondelli, V, Dazzan, J, Hepgul, N, Di Forti, M, Aas, M, D'Albenzio, A, Di Nicola, M, Fisher, H, Handley, R, Marques, T, Morgan, C, Navari, S, Taylor, H, Papadopoulos, A, Aitchinson, K, Murray, R, Pariante, C (2009). Abnormal cortisol levels during the day and cortisol awakening response in first-episode psychosis: the role of stress and of antipsychotic treatment. Schizophrenia Research 116, 234242.Google Scholar
Morgan, C, Fisher, H (2007). Environmental factors in schizophrenia: childhood trauma – a critical review. Schizophrenia Bulletin 33, 3–10.Google Scholar
O'Brien, SM, Scully, P, Scott, LV, Dinan, TG (2006). Cytokine profiles in bipolar affective disorder: focus on acutely ill patients. Journal of Affective Disorders 90, 263267.Google Scholar
O'Mahony, SM, Marchesi, JR, Scully, P, Codling, C, Ceolho, AM, Quigley, EM, Cryan, JF, Dinan, TG (2009). Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biological Psychiatry 65, 263267.Google Scholar
Opler, MG, Yang, LH, Caleo, S, Alberti, P (2007). Statistical validation of the criteria for symptom remission in schizophrenia: preliminary findings. BMC Psychiatry 7, 35.Google Scholar
Pace, TWW, Mletzko, TC, Alagbe, O, Musselman, DL, Nemeroff, CB, Miller, AH, Heim, CM (2006). Increased stress-induced inflammatory responses in male patients with major depression and increased early life stress. American Journal of Psychiatry 163, 16301633.CrossRefGoogle ScholarPubMed
Potvin, S, Stip, E, Sepehry, AA, Gendron, A, Bah, R, Kouassi, E (2008). Inflammatory cytokine alterations in schizophrenia: a systematic quantitative review. Biological Psychiatry 63, 801808.Google Scholar
Read, J, Perry, BD, Moskowitz, A, Connolly, J (2001). The contribution of early traumatic events to schizophrenia in some patients: a traumagenic neurodevelopmental model. Psychiatry 64, 319345.CrossRefGoogle ScholarPubMed
Read, J, van Os, J, Morrison, AP, Ross, CA (2005). Childhood trauma, psychosis and schizophrenia: a literature review with theoretical and clinical implications. Acta Psychiatrica Scandinavica 112, 330350.CrossRefGoogle ScholarPubMed
Shevlin, M, Dorahy, MJ, Adamson, G (2007). Trauma and psychosis: an analysis of the National Comorbidity Survey. American Journal of Psychiatry 164, 166169.CrossRefGoogle ScholarPubMed
Sparkman, N, Johnson, R (2008). Neuroinflammation associated with aging sensitizes the brain to the effects of infection or stress. Neuroimmunomodulation 15, 323330.CrossRefGoogle ScholarPubMed
Strous, RD, Shoenfeld, Y (2006). Schizophrenia, autoimmunity and immune system dysregulation: a comprehensive model updated and revisited. Journal of Autoimmunity 27, 7180.Google Scholar
Tandon, R, Keshavan, MS, Nasrallah, HA (2008). Schizophrenia, ‘just the facts’ what we know in 2008. 2. Epidemiology and etiology. Schizophrenia Research 102, 118.Google Scholar
Tienari, P, Wynne, LC, Sorri, A, Lahti, I, Läksy, K, Moring, J, Naarala, M, Nieminen, P, Wahlberg, K-E (2004). Genotype-environment interaction in schizophrenia-spectrum disorder. Long-term follow-up study of Finnish adoptees. British Journal of Psychiatry 184, 216222.CrossRefGoogle ScholarPubMed
Žarković, M, Ignjatović, S, Dajak, M, Ćirić, J, Beleslin, B, Savić, S, Stojković, M, Bulat, P, Trbojević, B (2008). Cortisol response to ACTH stimulation correlates with blood interleukin 6 concentration in healthy humans. European Journal of Endocrinology 159, 649652.CrossRefGoogle ScholarPubMed
Zhou, D, Kusnecov, A, Shurin, M, Depaoli, M, Rabin, B (1993). Exposure to physical and psychological stressors elevates plasma interleukin 6: relationship to the activation of hypothalamic-pituitary-adrenal axis. Endocrinology 133, 25232530.CrossRefGoogle Scholar