Hostname: page-component-586b7cd67f-dsjbd Total loading time: 0 Render date: 2024-11-27T21:43:41.194Z Has data issue: false hasContentIssue false
  • English
  • Français

The prospective association between stressful life events and inflammation among adolescents with a history of early institutional rearing

Published online by Cambridge University Press:  11 January 2021

Alva Tang ,
Mark Wade ,
Nathan A. Fox ,
Charles A. Nelson ,
Charles H. Zeanah  and
Natalie Slopen
Alva Tang*
Affiliation:
Department of Human Development and Quantitative Methodology, University of Maryland, College Park, MD, USA
Mark Wade
Affiliation:
Department of Applied Psychology and Human Development, University of Toronto, Toronto, ON, Canada
Nathan A. Fox
Affiliation:
Department of Human Development and Quantitative Methodology, University of Maryland, College Park, MD, USA
Charles A. Nelson
Affiliation:
Boston Children's Hospital, Harvard Medical School, Boston, MA, USA Harvard Graduate School of Education, Cambridge, MA, USA
Charles H. Zeanah
Affiliation:
Tulane University School of Medicine, New Orleans, LA, USA
Natalie Slopen
Affiliation:
School of Public Health, University of Maryland, College Park, MD, USA
*
Author for Correspondence: Alva Tang, Department of Human Development and Quantitative Methodology, University of Maryland, College Park, MD, USA; E-mail: alvatang@umd.edu
Get access Rights & Permissions [Opens in a new window]

Abstract

Early adversity has been shown to sensitize individuals to the effects of later stress and enhance risk of psychopathology. Using a longitudinal randomized trial of foster care as an alternative to institutional care, we extend the stress sensitization hypothesis to examine whether early institutional rearing sensitizes individuals to stressful events in adolescence engendering chronic low-grade inflammation. At baseline, institutionalized children in Romania (ages 6–31 months) were randomly assigned to foster care or to remain in usual care within institutions. A group of never-institutionalized children was recruited as an in-country comparison sample. At ages 12 and 16, participants reported stressful events. At age 16, Interleukin-6 (IL-6) and C-reactive protein (CRP) were derived from blood spots. Among children assigned to care as usual, more stressful events at age 12, but not age 16, were associated with higher IL-6. In the same group, stressful events at age 16 were associated with higher CRP, though these effects attenuated after adjusting for covariates. These associations were not observed in the foster care or never-institutionalized groups. The findings suggest that heightened inflammation following stress exposure is one pathway through which early neglect could compromise physical health. In contrast, early family care might buffer against these risks.

Keywords

adolescenceinflammationneglectstressful life eventsstress sensitization
Type
Special Section 2: Early Adversity and Development: Contributions from the Field
Information
Development and Psychopathology , Volume 32 , Special Issue 5: Early Adversity, Stress, and Neurobehavioral Development: Honoring Megan R. Gunnar's Contributions to Developmental Science , December 2020 , pp. 1715 - 1724
Check for updates
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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

Al-Bahrani, M., Aldhafri, S., Alkharusi, H., Kazem, A., & Alzubiadi, A. (2013). Age and gender differences in coping style across various problems: Omani adolescents’ perspective. Journal of Adolescence, 36, 303–309.CrossRefGoogle ScholarPubMed
Almas, A. N., Degnan, K. A., Walker, O. L., Radulescu, A., Nelson, C. A., Zeanah, C. H., & Fox, N. A. (2015). The effects of early institutionalization and foster care intervention on children's social behaviors at the age of eight. Social Development, 24, 225–239.CrossRefGoogle Scholar
Alumran, J. I., & Punamäki, R.-L. (2008). Relationship between gender, age, academic achievement, emotional intelligence, and coping styles in Bahraini adolescents. Individual Differences Research, 6, 104–109.Google Scholar
Baumeister, D., Akhtar, R., Ciufolini, S., Pariante, C. M., & Mondelli, V. (2016). 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
Blakemore, S. J., & Choudhury, S. (2006). Development of the adolescent brain: Implications for executive function and social cognition. Journal of Child Psychology and Psychiatry, 47, 296–312.CrossRefGoogle ScholarPubMed
Blakemore, S.-J., & Mills, K. L. (2014). Is adolescence a sensitive period for sociocultural processing? Annual Review of Psychology, 65, 187–207.10.1146/annurev-psych-010213-115202CrossRefGoogle ScholarPubMed
Bond, M. M., & Richards-Kortum, R. R. (2015). Drop-to-drop variation in the cellular components of fingerprick blood: Implications for point-of-care diagnostic development. American Journal of Clinical Pathology, 144, 885–894.CrossRefGoogle ScholarPubMed
Brown, B. B. (2004). Adolescents’ relationships with peers. Handbook of Adolescent Psychology, 2, 363–394.CrossRefGoogle Scholar
Brown, D. W., Anda, R. F., Tiemeier, H., Felitti, V. J., Edwards, V. J., Croft, J. B., & Giles, W. H. (2009). Adverse childhood experiences and the risk of premature mortality. American Journal of Preventive Medicine, 37, 389–396. doi.org/10.1016/j.amepre.2009.06.021CrossRefGoogle ScholarPubMed
Broyles, S. T., Staiano, A. E., Drazba, K. T., Gupta, A. K., Sothern, M., & Katzmarzyk, P. T. (2012). Elevated C-reactive protein in children from risky neighborhoods: Evidence for a stress pathway linking neighborhoods and inflammation in children. PLoS One, 7, e45419.CrossRefGoogle ScholarPubMed
Chiang, J. J., Chen, E., & Miller, G. E. (2018). Midlife self-reported social support as a buffer against premature mortality risks associated with childhood abuse. Nature Human Behaviour, 2, 261–268.CrossRefGoogle ScholarPubMed
Cicchetti, D., & Rogosch, F. A. (2002). A developmental psychopathology perspective on adolescence. Journal of Consulting and Clinical Psychology, 70, 6–20.CrossRefGoogle ScholarPubMed
Coddington, R. D. (1972). The significance of life events as etiologic factors in the diseases of children – II a study of a normal population. Journal of Psychosomatic Research, 16, 205–213.CrossRefGoogle Scholar
Coelho, R., Viola, T., Walss-Bass, C., Brietzke, E., & Grassi-Oliveira, R. (2014). Childhood maltreatment and inflammatory markers: A systematic review. Acta Psychiatrica Scandinavica, 129, 180–192.CrossRefGoogle ScholarPubMed
Crone, E. A., & Dahl, R. E. (2012). Understanding adolescence as a period of social–affective engagement and goal flexibility. Nature Reviews Neuroscience, 13, 636–650.10.1038/nrn3313CrossRefGoogle ScholarPubMed
Danese, A., Moffitt, T. E., Harrington, H., Milne, B. J., Polanczyk, G., Pariante, C. M., … Caspi, A. (2009). Adverse childhood experiences and adult risk factors for age-related disease: Depression, inflammation, and clustering of metabolic risk markers. Archives of Pediatrics & Adolescent Medicine, 163, 1135–1143.CrossRefGoogle ScholarPubMed
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, 1319–1324.CrossRefGoogle Scholar
Daskalakis, N. P., Bagot, R. C., Parker, K. J., Vinkers, C. H., & de Kloet, E. R. (2013). The three-hit concept of vulnerability and resilience: Toward understanding adaptation to early-life adversity outcome. Psychoneuroendocrinology, 38, 1858–1873.10.1016/j.psyneuen.2013.06.008CrossRefGoogle ScholarPubMed
Debnath, R., Tang, A., Zeanah, C. H., Nelson, C. A., & Fox, N. A. (2019). The Long-term effects of institutional rearing, foster care intervention and disruptions in care on brain electrical activity in adolescence. Developmental Science, 23(1), e12872.Google ScholarPubMed
Del Giudice, M., & Gangestad, S. W. (2018). Rethinking IL-6 and CRP: Why they are more than inflammatory biomarkers, and why it matters. Brain, Behavior, and Immunity, 70, 61–75.CrossRefGoogle ScholarPubMed
Donath, M. Y., & Shoelson, S. E. (2011). Type 2 diabetes as an inflammatory disease. Nature Reviews Immunology, 11, 98–107.CrossRefGoogle ScholarPubMed
Dougherty, L. R., Klein, D. N., & Davila, J. (2004). A growth curve analysis of the course of dysthymic disorder: The effects of chronic stress and moderation by adverse parent-child relationships and family history. Journal of Consulting and Clinical Psychology, 72, 1012–1021.CrossRefGoogle ScholarPubMed
Ehrlich, K. B., Ross, K. M., Chen, E., & Miller, G. E. (2016). Testing the biological embedding hypothesis: Is early life adversity associated with a later proinflammatory phenotype? Development and Psychopathology, 28, 1273–1283.CrossRefGoogle ScholarPubMed
Enders, C. K., & Bandalos, D. L. (2001). The relative performance of full information maximum likelihood estimation for missing data in structural equation models. Structural Equation Modeling, 8, 430–457.CrossRefGoogle Scholar
Espejo, E. P., Hammen, C. L., Connolly, N. P., Brennan, P. A., Najman, J. M., & Bor, W. (2007). Stress sensitization and adolescent depressive severity as a function of childhood adversity: A link to anxiety disorders. Journal of Abnormal Child Psychology, 35, 287–299.CrossRefGoogle ScholarPubMed
Felitti, V. J., Anda, R. F., Nordenberg, D., Williamson, D. F., Spitz, A. M., & Edwards, V. (1998). Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults: The adverse childhood experiences (ACE) Study. American Journal of Preventive Medicine, 14, 245–258. doi:10.1016/s0749-3797(98)00017-8CrossRefGoogle ScholarPubMed
Furman, W., & ShaVer, L. (2003). The role of romantic relationships in adolescent development. In Furman, W., & Shaffer, L. (Eds.), Adolescent romantic relations and sexual behavior (pp. 17–36). Mahwah, NJ: Psychology Press.Google Scholar
Fuster, J. J., & Walsh, K. (2014). The good, the bad, and the ugly of interleukin-6 signaling. The EMBO Journal, 33, 1425–1427.CrossRefGoogle ScholarPubMed
Gabay, C. (2006). Interleukin-6 and chronic inflammation. Arthritis Research & Therapy, 8, S3.CrossRefGoogle ScholarPubMed
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, 287–292.CrossRefGoogle ScholarPubMed
Guyer, A. E., Silk, J. S., & Nelson, E. E. (2016). The neurobiology of the emotional adolescent: From the inside out. Neuroscience & Biobehavioral Reviews, 70, 74–85.CrossRefGoogle ScholarPubMed
Hammen, C., Henry, R., & Daley, S. E. (2000). Depression and sensitization to stressors among young women as a function of childhood adversity. Journal of Consulting and Clinical Psychology, 68, 782–787. doi:10.1037/0022-006x.68.5.782CrossRefGoogle ScholarPubMed
Hampel, P., & Petermann, F. (2006). Perceived stress, coping, and adjustment in adolescents. Journal of Adolescent Health, 38, 409–415.CrossRefGoogle ScholarPubMed
Harkness, K. L., Bruce, A. E., & Lumley, M. N. (2006). The role of childhood abuse and neglect in the sensitization to stressful life events in adolescent depression. Journal of Abnormal Psychology, 115, 730–741.CrossRefGoogle ScholarPubMed
Harrington, R. A. (2017). Targeting inflammation in coronary artery disease. New England Journal of Medicine, 377, 1197–1198.CrossRefGoogle ScholarPubMed
Harris, K. M., & Udry, J. R. (2018). National longitudinal study of adolescent to adult health (add health), 1994-2008 [Public Use]. Ann Arbor, MI: Carolina Population Center, University of North Carolina-Chapel Hill [distributor], Inter-university Consortium for Political and Social Research [distributor]. 08-06.Google Scholar
Hertzman, C. (1999). The biological embedding of early experience and its effects on health in adulthood. Annals of the New York Academy of Sciences, 896, 85–95.CrossRefGoogle ScholarPubMed
Horn, S. R., Long, M. M., Nelson, B. W., Allen, N. B., Fisher, P. A., & Byrne, M. L. (2018). Replication and reproducibility issues in the relationship between C-reactive protein and depression: A systematic review and focused meta-analysis. Brain, Behavior, and Immunity, 73, 85–114.CrossRefGoogle ScholarPubMed
John-Henderson, N. A., Marsland, A. L., Kamarck, T. W., Muldoon, M. F., & Manuck, S. B. (2016). Childhood SES and the occurrence of recent negative life events as predictors of circulating and stimulated levels of Interleukin-6. Psychosomatic Medicine, 78, 91–101.CrossRefGoogle ScholarPubMed
Johnston, L. D., O'Malley, P. M., Miech, R. A., Bachman, J. G., & Schulenberg, J. E. (2017). Monitoring the Future National Survey Results on Drug Use, 1975-2016: Overview, key findings on adolescent drug use. Ann Arbor: Institute for Social Research, The University of Michigan.Google Scholar
Kendler, K. S., Kuhn, J. W., & Prescott, C. A. (2004). Childhood sexual abuse, stressful life events and risk for major depression in women. Psychological Medicine, 34, 1475–1482.CrossRefGoogle ScholarPubMed
Kiecolt-Glaser, J. K., Gouin, J.-P., Weng, N.-p., Malarkey, W. B., Beversdorf, D. Q., & Glaser, R. (2011). Childhood adversity heightens the impact of later-life caregiving stress on telomere length and inflammation. Psychosomatic Medicine, 73, 16–22. doi:10.1097/PSY.0b013e31820573b6CrossRefGoogle ScholarPubMed
Kuhlman, K. R., Horn, S. R., Chiang, J. J., & Bower, J. E. (2019). Early life adversity exposure and circulating markers of inflammation in children and adolescents: A systematic review and meta-analysis. Brain, Behavior, and Immunity, 86, 30–42.CrossRefGoogle Scholar
Kuo, H.-K., Yen, C.-J., Chang, C.-H., Kuo, C.-K., Chen, J.-H., & Sorond, F. (2005). Relation of C-reactive protein to stroke, cognitive disorders, and depression in the general population: Systematic review and meta-analysis. The Lancet Neurology, 4, 371–380.CrossRefGoogle ScholarPubMed
La Rocque, C. L., Harkness, K. L., & Bagby, R. M. (2014). The differential relation of childhood maltreatment to stress sensitization in adolescent and young adult depression. Journal of Adolescence, 37, 871–882.CrossRefGoogle ScholarPubMed
Lenhart, A. (2009). Teens and mobile phones over the past five years: Pew Internet looks back: Pew Internet & American Life Project Washington, DC.Google Scholar
McDade, T. W., Burhop, J., & Dohnal, J. (2004). High-sensitivity enzyme immunoassay for C-reactive protein in dried blood spots. Clinical Chemistry, 50, 652–654.CrossRefGoogle ScholarPubMed
McLaughlin, K. A., Conron, K. J., Koenen, K. C., & Gilman, S. E. (2010). Childhood adversity, adult stressful life events, and risk of past-year psychiatric disorder: A test of the stress sensitization hypothesis in a population-based sample of adults. Psychological Medicine, 40, 1647–1658.CrossRefGoogle Scholar
McLaughlin, K. A., Sheridan, M. A., Tibu, F., Fox, N. A., Zeanah, C. H., & Nelson, C. A. (2015). Causal effects of the early caregiving environment on development of stress response systems in children. Proceedings of the National Academy of Sciences, 112(18), 5637–5642.CrossRefGoogle ScholarPubMed
Miller, G. E., & Chen, E. (2010). Harsh family climate in early life presages the emergence of a proinflammatory phenotype in adolescence. Psychological Science, 21, 848–856.CrossRefGoogle ScholarPubMed
Miller, G. E., Chen, E., & Parker, K. J. (2011). Psychological stress in childhood and susceptibility to the chronic diseases of aging: Moving toward a model of behavioral and biological mechanisms. Psychological Bulletin, 137, 959–997.CrossRefGoogle Scholar
Miller, E. M., & McDade, T. W. (2012). A highly sensitive immunoassay for interleukin-6 in dried blood spots. American Journal of Human Biology, 24, 863–865.CrossRefGoogle ScholarPubMed
National Academies of Sciences, E., & Medicine. (2019). The promise of adolescence: Realizing opportunity for all youth. Washington, DC: National Academies Press.Google Scholar
O'Connor, T. G., Willoughby, M. T., Moynihan, J. A., Messing, S., Sefair, A. V., Carnahan, J., … Caserta, M. T. (2019). Early childhood risk exposures and inflammation in early adolescence. Brain, Behavior, and Immunity, 86, 22–29.CrossRefGoogle ScholarPubMed
Plancherel, B., Bolognini, M., & Halfon, O. (1998). Coping strategies in early and mid-adolescence. European Psychologist, 3, 192–201.CrossRefGoogle Scholar
Pradhan, A. D., Manson, J. E., Rifai, N., Buring, J. E., & Ridker, P. M. (2001). C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA, 286, 327–334.CrossRefGoogle ScholarPubMed
Reid, B. M., Coe, C. L., Doyle, C. M., Sheerar, D., Slukvina, A., Donzella, B., & Gunnar, M. R. (2019). Persistent skewing of the T-cell profile in adolescents adopted internationally from institutional care. Brain, Behavior, and Immunity, 77, 168–177.CrossRefGoogle ScholarPubMed
Rosseel, Y. (2012). Lavaan: An R package for structural equation modeling and more. Version 0.5–12 (BETA). Journal of Statistical Software, 48, 1–36.CrossRefGoogle Scholar
Savolainen, K., Eriksson, J. G., Kananen, L., Kajantie, E., Pesonen, A.-K., Heinonen, K., & Räikkönen, K. (2014). Associations between early life stress, self-reported traumatic experiences across the lifespan and leukocyte telomere length in elderly adults. Biological Psychology, 97, 35–42. doi.org/10.1016/j.biopsycho.2014.02.002CrossRefGoogle ScholarPubMed
Schmeer, K. K., & Yoon, A. (2016). Socioeconomic status inequalities in low-grade inflammation during childhood. Archives of Disease in Childhood, 101, 1043–1047.CrossRefGoogle ScholarPubMed
Shonkoff, J. P., Boyce, W. T., & McEwen, B. S. (2009). Neuroscience, molecular biology, and the childhood roots of health disparities: Building a new framework for health promotion and disease prevention. JAMA, 301, 2252–2259.CrossRefGoogle ScholarPubMed
Simons, R. L., Woodring, D., Simons, L. G., Sutton, T. E., Lei, M.-K., Beach, S. R., … Gibbons, F. X. (2019). Youth adversities amplify the association between adult stressors and chronic inflammation in a domain specific manner: Nuancing the early life sensitivity model. Journal of Youth and Adolescence, 48, 1–16.CrossRefGoogle Scholar
Sin, N. L., Graham-Engeland, J. E., Ong, A. D., & Almeida, D. M. (2015). Affective reactivity to daily stressors is associated with elevated inflammation. Health Psychology, 34, 1154.CrossRefGoogle ScholarPubMed
Slopen, N., Kubzansky, L. D., & Koenen, K. C. (2011). Childhood adversity and inflammatory and immune biomarkers associated with cardiovascular risk in youth: A systematic review. Brain, Behavior, and Immunity, 26, 239–250. doi:10.1016/j.bbi.2011.11.003CrossRefGoogle ScholarPubMed
Slopen, N., Tang, A., Nelson, C. A., Zeanah, C. H., McDade, T. W., McLaughlin, K. A., & Fox, N. A. (2019). The consequences of foster care versus institutional care in early childhood on adolescent cardiometabolic and immune markers: Results from a randomized controlled trial. Psychosomatic Medicine, 81, 449–457.CrossRefGoogle ScholarPubMed
Smetana, J. G., Campione-Barr, N., & Metzger, A. (2006). Adolescent development in interpersonal and societal contexts. Annual Review of Psychology, 57, 255–284.CrossRefGoogle ScholarPubMed
Steinberg, L. (2015). How to improve the health of American adolescents. Perspectives on Psychological Science, 10, 711–715.CrossRefGoogle ScholarPubMed
Tang, A., Fox, N. A., Nelson, C. A., Zeanah, C. H., & Slopen, N. (2019). Externalizing trajectories predict elevated inflammation among adolescents exposed to early institutional rearing: A randomized clinical trial. Psychoneuroendocrinology, 109, 104408.CrossRefGoogle ScholarPubMed
Wade, M., Fox, N. A., Zeanah, C. H., & Nelson, C. A. (2019a). Long-term effects of institutional rearing, foster care, and brain activity on memory and executive functioning. Proceedings of the National Academy of Sciences, 116, 1808–1813.CrossRefGoogle Scholar
Wade, M., Zeanah, C. H., Fox, N. A., Tibu, F., Ciolan, L. E., & Nelson, C. A. (2019b). Stress sensitization among severely neglected children and protection by social enrichment. Nature Communications, 10, 1–8.CrossRefGoogle Scholar
Young, E. S., Farrell, A. K., Carlson, E. A., Englund, M. M., Miller, G. E., Gunnar, M. R., … Simpson, J. A. (2019). The dual impact of early and concurrent life stress on adults’ diurnal cortisol patterns: A prospective study. Psychological Science, 30, 739–747.CrossRefGoogle ScholarPubMed
Zeanah, C. H., Nelson, C. A., Fox, N. A., Smyke, A. T., Marshall, P., Parker, S. W., & Koga, S. (2003). Designing research to study the effects of institutionalization on brain and behavioral development: The Bucharest Early Intervention Project. Development and Psychopathology, 15, 885–907.CrossRefGoogle Scholar