Studying the Relationship between Childhood Maltreatment and Inflammatory Biomarkers in Adulthood from a Psychoneuroimmunological Perspective: A Meta-Analysis

Document Type : Research Paper


1 Department of Psychology, Psychology and Educational Science Faculty, University of Tehran, Tehran, Iran

2 Department of Education, Psychology and Educational Science Faculty, University of Tehran, Tehran, Iran

3 Medical sciences Faculty, Tehran University of Tehran, Iran


This study was conducted since inflammation is one of the underlying mechanisms of many autoimmune diseases, cardiovascular diseases, type 2 diabetes, etc. The aim of this study is to collect and compare research findings on the relationship between childhood maltreatment and attachment styles with the level of CRP-IL-6 inflammatory markers. A systematic search of Pub Med, Springer, and Elsevier from 2000 to 2019 yielded approximately 30 English-language papers. Finally, 11 papers met the research criteria and were included. In the included studies, a total of 16,867 subjects were screened for CRP inflammatory markers and 6728 subjects were screened for IL-6 markers. And the random effect meta-analysis results show that people who were exposed to abuse as children, childhood maltreatment, or severe stress or psychological trauma had significantly higher baseline CRP (Z = 3.2, 95% CI= 0.05-0.09) and more IL-6 (Z = 3.1, 95%CI = 0.19-3.19) in adulthood. This systematic review suggests that the experience of severe abuse and stress in childhood contributes to the development of preinflammatory conditions in adulthood. Given the sensitivity and importance of this topic, further research is needed to elucidate many intermediary mechanisms.


Allen, M. S., & Laborde, S. (2017). Five factor personality traits and inflammatory biomarkers in the English longitudinal study of aging. Personality and Individual Differences111(8), 205-210.
Archer, J. A., Hutchison, I. L., Dorudi, S., Stansfeld, S. A., & Korszun, A. (2012). Interrelationship of depression, stress and inflammation in cancer patients: A preliminary study. Journal of Affective Disorders. 143(1-3), 39-46.
Barbosa, F., Ferreira, C., Patrício, P., Mota, C., Alcântara, C., & Barbosa, A. (2010). Attachment style in patients with systemic lupus erythematosus. Acta Medica Portuguesa. 23(1), 51-62.
Bertone-Johnson, E. R., Whitcomb, B. W., Missmer, S. A., Karlson, E. W., & Rich-Edwards, J. W. (2012). Inflammation and early-life abuse in women. American Journal of Preventive Medicine. 43(6), 611-620.
Calcia, M. A., Bonsall, D. R., Bloomfield, P. S., Selvaraj, S., Barichello, T., & Howes, O. D. (2016). Stress and neuroinflammation: A systematic review of the effects of stress on microglia and the implications for mental illness. Psychopharmacology. 233(9), 1637-1650.
Carpenter, L. L., Gawuga, C. E., Tyrka, A. R., Lee, J. K., Anderson, G. M., & Price, L. H. (2010). Association between plasma IL-6 response to acute stress and early-life adversity in healthy adults. Neuropsychopharmacology35(13), 2617-2623.
Chapman, D. P., Whitfield, C. L., Felitti, V. J., Dube, S. R., Edwards, V. J., & Anda, R. F. (2004). Adverse childhood experiences and the risk of depressive disorders in adulthood. Journal of Affective Disorders. 82(2), 217-225.
Chen, M., & Lacey, R. E. (2018). Adverse childhood experiences and adult inflammation: Findings from the 1958 British birth cohort. Brain, Behavior, and Immunity. 69(9), 582-590.
Chida, D., & Iwakura, Y. (2007). Peripheral TNFα, but not peripheral IL-1, requires endogenous IL-1 or TNFα induction in the brain for the febrile response. Biochemical and Biophysical Research Communications364(4), 765-770.
Coelho, R., Viola, T. W., Walss Bass, C., Brietzke, E., & Grassi‐Oliveira, R. (2014). Childhood maltreatment and inflammatory markers: a systematic review. Acta Psychiatrica Scandinavica. 129(3), 180-192.
Cohen, S. (2004). Social relationships and health. American Psychologist. 59(8), 676-684
Danese, A., Pariante, C. M., Caspi, A., Taylor, A., & Poulton, R. (2007). Childhood maltreatment predicts adult inflammation in a life-course study. Proceedings of the National Academy of Sciences. 104(4), 1319-1324.
Dhabhar, F. S. (2009). A hassle a day may keep the pathogens away: the fight-or-flight stress response and the augmentation of immune function. Integrative and Comparative Biology. 49(3), 215-236.
Egger, M., Smith, G. D., & Phillips, A. N. (1997). Meta-analysis: Principles and procedures. Bmj. 315(7121), 1533-1537.
Ehrlich, K. B., Stern, J. A., Eccles, J., Dinh, J. V., Hopper, E. A., Kemeny, M. E., …, & Cassidy, J. (2019). A preliminary investigation of attachment style and inflammation in African-American young adults. Attachment & Human Development. 21(1), 57–69.
Ehrlich K. B., & Cassidy J. (2019) Attachment and physical health: introduction to the special issue. Attachment & Human Development, 21(1), 1-4.
Gouin, J. P., Glaser, R., Malarkey, W. B., Beversdorf, D., & Kiecolt-Glaser, J. K. (2012). Childhood abuse and inflammatory responses to daily stressors. Annals of Behavioral Medicine. 44(2), 287-292.
Hennessy, M. B., Deak, T., Schiml-Webb, P. A., Wilson, S. E., Greenlee, T. M., & McCall, E. (2004). Responses of guinea pig pups during isolation in a novel environment may represent stress-induced sickness behaviors. Physiology & Behavior. 81(1), 5-13.
Hennessy, M. B., Deak, T., Schiml-Webb, P. A., Carlisle, C. W., & O'Brien, E. (2010). Maternal separation produces, and a second separation enhances, core temperature and passive behavioral responses in guinea pig pups. Physiology & Behavior. 100(4), 305-310.
Higgins, J. P., & Thompson, S. G. (2002). Quantifying heterogeneity in a meta-analysis. Statistics in Medicine. 21(11), 1539-1558.
Holt-Lunstad, J., Smith, T. B., & Layton, J. B. (2010). Social relationships and mortality risk: A meta-analytic review. PLoS Medicine. 7(7), e1000316.
Janusek, L. W., Tell, D., Albuquerque, K., & Mathews, H. L. (2013). Childhood adversity increases vulnerability for behavioral symptoms and immune dysregulation in women with breast cancer. Brain, Behavior, and Immunity. 30, S149-S162.
Kiecolt-Glaser, J. K., Gouin, J. P., & Hantsoo, L. (2010). Close relationships, inflammation, and health. Neuroscience & Biobehavioral Reviews. 35(1), 33-38.
Kim, Y. K., Na, K. S., Shin, K. H., Jung, H. Y., Choi, S. H., & Kim, J. B. (2007). Cytokine imbalance in the pathophysiology of major depressive disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 31(5), 1044-1053.
Liu, Y. Z., Wang, Y. X., & Jiang, C. L. (2017). Inflammation: the common pathway of stress-related diseases. Frontiers in Human Neuroscience. 11(6), 316-323.
McDade, T. W., Hoke, M., Borja, J. B., Adair, L. S., & Kuzawa, C. (2013). Do environments in infancy moderate the association between stress and inflammation in adulthood? Initial evidence from a birth cohort in the Philippines. Brain, Behavior, and Immunity. 31, 23-30.
McLaughlin, K. A. (2016). Future directions in childhood adversity and youth psychopathology. Journal of Clinical Child & Adolescent Psychology. 45(3), 361-382.
Miller, A. H., Maletic, V., & Raison, C. L. (2009). Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biological Psychiatry. 65(9), 732-741.
Miller, G., Rohleder, N., & Cole, S. W. (2009). Chronic interpersonal stress predicts activation of pro-and anti-inflammatory signaling pathways six months later. Psychosomatic Medicine71(1), 57-64.
Mok, C. C., & Lau, C. S. (2003). Pathogenesis of systemic lupus erythematosus. Journal of Clinical Pathology. 56(7), 481-490.
Robles, T. F., Slatcher, R. B., Trombello, J. M., & McGinn, M. M. (2014). Marital quality and health: a meta-analytic review. Psychological Bulletin. 140(1), 140-151.
Rohleder, N. (2014). Stimulation of systemic low-grade inflammation by psychosocial stress. Psychosomatic Medicine76(3), 181-189.
Slopen, N., Kubzansky, L. D., McLaughlin, K. A., & Koenen, K. C. (2013). Childhood adversity and inflammatory processes in youth: a prospective study. Psychoneuroendocrinology. 38(2), 188-200.
Tyrka, A. R., Burgers, D. E., Philip, N. S., Price, L. H., & Carpenter, L. L. (2013). The neurobiological correlates of childhood adversity and implications for treatment. Acta Psychiatrica Scandinavica. 128(6), 434-447.
Whisman, M. A. (2017). Interpersonal perspectives on depression. The Oxford handbook of mood disorders, Oxford University Press: New York (pp. 167-178).
Wong, W. C., Cheung, C. S., & Hart, G. J. (2008). Development of a quality assessment tool for systematic reviews of observational studies (QATSO) of HIV prevalence in men having sex with men and associated risk behaviours. Emerging Themes in Epidemiology5(1), 1-4.
Zeugmann, S., Buehrsch, N., Bajbouj, M., Heuser, I., Anghelescu, I., & Quante, A. (2013). Childhood maltreatment and adult proinflammatory status in patients with major depression. Psychiatria Danubina. 25(3), 227-235.