Hostname: page-component-76fb5796d-25wd4 Total loading time: 0 Render date: 2024-04-27T03:27:38.466Z Has data issue: false hasContentIssue false
  • English
  • Français

Testing the biological embedding hypothesis: Is early life adversity associated with a later proinflammatory phenotype?

Published online by Cambridge University Press:  03 October 2016

Katherine B. Ehrlich ,
Kharah M. Ross ,
Edith Chen  and
Gregory E. Miller
Katherine B. Ehrlich*
Affiliation:
University of Georgia
Kharah M. Ross
Affiliation:
University of California at Los Angeles
Edith Chen
Affiliation:
Northwestern University
Gregory E. Miller
Affiliation:
Northwestern University
*
Address correspondence and reprint requests to: Katherine B. Ehrlich, Department of Psychology and Center for Family Research, University of Georgia, Athens, GA 30602; E-mail: kehrlich@uga.edu.
Get access Rights & Permissions [Opens in a new window]

Abstract

Accumulating evidence suggests that the experience of early life adversity is a risk factor for a range of poor outcomes across development, including poor physical health in adulthood. The biological embedding model of early adversity (Miller, Chen, & Parker, 2011) suggests that early adversity might become embedded within immune cells known as monocytes/macrophages, programming them to be overly aggressive to environmental stimuli and insensitive to inhibitory signals, creating a “proinflammatory phenotype” that increases vulnerability to chronic diseases across the life span. We tested this hypothesis in the present study. Adolescent girls (n = 147) had blood drawn every 6 months across a 2.5-year period. To assess inflammatory responses to challenge, their monocytes were stimulated in vitro with a bacterial product, and production of the cytokine interleukin-6 was quantified. Hydrocortisone was added to cultures to assess the cells’ sensitivity to glucocorticoids’ anti-inflammatory signal. Using cluster analyses, we found that early life adversity was associated with greater odds of displaying a proinflammatory phenotype characterized by relatively larger interleukin-6 responses and relatively less sensitivity to glucocorticoids. In contrast, ongoing social stress was not associated with increasing odds of being categorized in the proinflammatory cluster. These findings suggest that early life adversity increases the probability of developing a proinflammatory phenotype, which, if sustained, could forecast risk for health problems later in life.

Type
Special Section Articles
Information
Development and Psychopathology , Volume 28 , Special Issue 4pt2: Epigenetics: Development, Psychopathology, Resilience, and Preventive Intervention , November 2016 , pp. 1273 - 1283
Copyright
Copyright © Cambridge University Press 2016 

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

Appleyard, K., Egeland, B., van Dulmen, M. H. M., & Sroufe, L. A. (2005). When more is not better: The role of cumulative risk in child behavior outcomes. Journal of Child Psychology and Psychiatry, 46, 235–245.CrossRefGoogle Scholar
Azad, M. B., Lissitsyn, Y., Miller, G. E., Becker, A. B., HayGlass, K. T., & Kozyrskyj, A. L. (2012). Influence of socioeconomic status trajectories on innate immune responsiveness in children. PLOS ONE, 7, e38669.CrossRefGoogle ScholarPubMed
Barker, D. J. (1992). Fetal and infant origins of adult disease. London: BMJ Publishing Group.Google Scholar
Black, J. E., Jones, T. A., Nelson, C. A., & Greenough, W. T. (1998). Neuronal plasticity and the developing brain. In Alessi, N. E., Coyle, J. T., Harrison, S. I., & Eth, S. (Eds.), Handbook of child and adolescent psychiatry: Vol. 6. Basic psychiatric science and treatment (pp. 31–53). New York: Wiley.Google Scholar
Blair, C., & Raver, C. C. (2012). Child development in the context of adversity: Experiential canalization of brain and behavior. American Psychologist, 67, 309–318.Google Scholar
Busillo, J. M., & Cidlowski, J. A. (2013). The five Rs of glucocorticoid action during inflammation: Ready, reinforce, repress, resolve, and restore. Trends in Endocrinology & Metabolism, 24, 109–119.Google Scholar
Cameron, N. M., Champagne, F. A., Parent, C., Fish, E. W., Ozaki-Kuroda, K., & Meaney, M. J. (2005). The programming of individual differences in defensive responses and reproductive strategies in the rat through variations in maternal care. Neuroscience & Biobehavioral Reviews, 29, 843–865.Google Scholar
Chen, E., Langer, D. A., Raphaelson, Y. E., & Matthews, K. A. (2004). Socioeconomic status and health in adolescents: The role of stress interpretations. Child Development, 75, 1039–1052.CrossRefGoogle ScholarPubMed
Children's Defense Fund. (2012). The state of America's children. Washington, DC: Author.Google Scholar
Coe, C. L., & Lubach, G. R. (2007). Mother–infant interactions and the development of immunity from conception through weaning. In Ader, R. (Ed.), Psychoneuroimmunology (4th ed., pp. 455–474). London: Academic Press.CrossRefGoogle Scholar
Csikszentmihalyi, M., & Larson, R. (1984). Being adolescent: Conflict and growth in the teenage years. New York: Basic Books.Google Scholar
Danesh, J., Collins, R., Appleby, P., & Peto, R. (1998). Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: Meta-analyses of prospective studies. Journal of the American Medical Association, 279, 1477–1482.CrossRefGoogle ScholarPubMed
Dixon, D., Meng, H., Goldberg, R., Schneiderman, N., & Delamater, A. (2009). Stress and body mass index each contributes independently to tumor necrosis factor-production in prepubescent Latino children. Journal of Pediatric Nursing, 24, 378–388.Google Scholar
Dodge, K. A., Pettit, G. S., & Bates, J. E. (1994). Socialization mediators of the relation between socioeconomic status and child conduct problems. Child Development, 65, 649–665.Google Scholar
Ehrlich, K. B., Miller, G. E., & Chen, E. (2016). Childhood adversity and adult physical health. In Cicchetti, D. (Ed.), Developmental psychopathology (3rd ed., Vol. 4, pp. 1–42). Hoboken, NJ: Wiley.Google Scholar
Ehrlich, K. B., Miller, G. E., Rohleder, N., & Adam, E. K. (2016). Trajectories of relationship stress and inflammatory processes in adolescence. Development and Psychopathology, 28, 127–138.Google Scholar
Fuligni, A. J., Telzer, E. H., Bower, J., Cole, S. W., Kiang, L., & Irwin, M. R. (2009). A preliminary study of daily interpersonal stress and C-reactive protein levels among adolescents from Latin American and European backgrounds. Psychosomatic Medicine, 71, 329–333.Google Scholar
Furman, W., & Buhrmester, D. (1992). Age and sex differences in the perceptions of networks of personal relationships. Child Development, 63, 103–115.Google Scholar
Furman, W., & Shaffer, L. (2003). The role of romantic relationships in adolescent development. In Florsheim, P. (Ed.), Adolescent romantic relations and sexual behavior: Theory, research, and practical implications (pp. 3–22). Mahwah, NJ: Erlbaum.Google Scholar
Gluckman, P. D., & Hanson, M. A. (2006). The conceptual basis for developmental origins of health and disease. In Gluckman, P. & Hanson, M. (Eds.), Developmental origins of health and disease (pp. 33–50). New York: Cambridge University Press.Google Scholar
Graham, J. (2009). Missing data analysis: Making it work in the real world. Annual Review of Psychology, 60, 549–576.Google Scholar
Hammen, C. (1991). The generation of stress in the course of unipolar depression. Journal of Abnormal Psychology, 100, 555–561.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.Google Scholar
Hotamisligil, G. S. (2006). Inflammation and metabolic disorders. Nature, 444, 860–867.Google Scholar
Jelicic, H., Phelps, E., & Lerner, R. (2009). Use of missing data methods in longitudinal studies: The persistence of bad practices in developmental psychology. Developmental Psychology, 45, 1195–1199.Google Scholar
John-Henderson, N. A., Marsland, A. L., Kamarck, T. W., Muldoon, M. F., & Manuck, S. B. (2016). Childhood socioeconomic status and the occurrence of recent negative life events as predictors of circulating and stimulated levels of IL-6. Psychosomatic Medicine, 78, 91–101.CrossRefGoogle Scholar
Kaptoge, S., Di Angelantonio, E., Lowe, G., Pepys, M. B., Thompson, S. G., Collins, R., et al. (2010). C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: An individual participant meta-analysis. Lancet, 375, 132–140.Google ScholarPubMed
Kessler, R. C., Davis, C. G., & Kendler, K. S. (1997). Childhood adversity and adult psychiatry disorder in the U.S. National Comorbidity Survey. Psychological Medicine, 27, 1101–1119.Google Scholar
Kessler, R. C., McLaughlin, K. A., Green, J. G., Gruber, M. J., Sampson, N. A., Zaslavsky, A. M., et al. (2010). Childhood adversities and adult psychopathology in the WHO World Mental Health Surveys. British Journal of Psychiatry, 197, 378–385.CrossRefGoogle ScholarPubMed
Kiecolt-Glaser, J. K., Gouin, J. P., & Hantsoo, L. (2010). Close relationships, inflammation, and health. Neuroscience & Biobehavioral Reviews, 35, 33–38.Google Scholar
Libby, P., Ridker, P. M., & Hansson, G. K. (2009). Inflammation in atherosclerosis: From pathophysiology to practice. Journal of the American College of Cardiology, 54, 2129–2138.Google Scholar
Libby, P., & Theroux, P. (2005). Pathophysiology of coronary artery disease. Circulation, 111, 3481–3488.Google Scholar
Lupien, S. J., McEwen, B. S., Gunnar, M. R., & Heim, C. (2009). Effects of stress throughout the lifespan on the brain, behavior and cognition. Nature Reviews Neuroscience, 10, 434–445.CrossRefGoogle Scholar
Lynch, J., & Smith, G. D. (2005). A life course approach to chronic disease epidemiology. Annual Review of Public Health, 26, 1–35.Google Scholar
Markham, J. A., & Koenig, J. I. (2011). Prenatal stress: Role in psychotic and depressive diseases. Psychopharmacology, 214, 89–106.Google Scholar
Marques, A. H., Silverman, M. N., & Sternberg, E. M. (2009). Glucocorticoid dysregulations and their clinical correlates: From receptors to therapeutics. Annals of the New York Academy of Sciences, 1179, 1–18.Google Scholar
McEwen, B. S., & Seeman, T. (1999). Protective and damaging effects of mediators of stress: Elaborating and testing the concepts of allostasis and allostatic load. Annals of the New York Academy of Sciences, 896, 30–47.Google Scholar
Meaney, M. J. (2001). Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annual Review of Neuroscience, 24, 1161–1192.Google Scholar
Meyer, U., Feldon, J., & Dammann, O. (2011). Schizophrenia and autism: Both shared and disorder-specific pathogenesis via perinatal inflammation? Pediatric Research, 69, 26R–33R.CrossRefGoogle ScholarPubMed
Miller, G. E., & Cole, S. W. (2012). Clustering of depression and inflammation in adolescents previously exposed to childhood adversity. Biological Psychiatry, 72, 34–40.CrossRefGoogle ScholarPubMed
Miller, G. E., Brody, G. H., Yu, T., & Chen, E. (2014). A family oriented psychosocial intervention reduces inflammation in low-SES African American youth. Proceedings of the National Academy of Sciences, 111, 11287–11292.Google Scholar
Miller, G. E., & Chen, E. (2013). The biological residue of childhood poverty. Child Development Perspectives, 7, 67–73.Google Scholar
Miller, G. E., Chen, E., Fok, A. K., Walker, H., Lim, A., Nicholls, E. F., et al. (2009). Low early-life social class leaves a biological residue manifested by decreased glucocorticoid and increased proinflammatory signaling. Proceedings of the National Academy of Sciences, 106, 14716–14721.Google Scholar
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.Google Scholar
Miller, G. E., Chen, E., Sze, J., Marin, T., Arevalo, J. M. G., Doll, R., et al. (2008). A genomic fingerprint of chronic stress in humans: Blunted glucocorticoid and increased NF-κB signaling. Biological Psychiatry, 64, 266–272.Google Scholar
Miller, G. E., Chen, E., & Zhou, E. S. (2007). If it goes up, must it come down? Chronic stress and the hypothalamic–pituitary–adrenocortical axis in humans. Psychological Bulletin, 133, 25–45.Google Scholar
Miller, G. E., Rohleder, N., & Cole, S. W. (2009). Chronic interpersonal stress predicts activation of pro- and anti-inflammatory signaling pathways six months later. Psychosomatic Medicine, 71, 57–62.Google Scholar
Murphy, M. L. M., Slavich, G. M., Chen, E., & Miller, G. E. (2015). Targeted rejection predicts decreased anti-inflammatory gene expression and increased symptom severity in youth with asthma. Psychological Science, 26, 111–121.Google Scholar
Murphy, M. L. M., Slavich, G. M., Rohleder, N., & Miller, G. E. (2013). Targeted rejection triggers differential pro- and anti-inflammatory gene expression in adolescents as a function of social status. Clinical Psychological Science, 1, 30–40.Google Scholar
Nathan, C., & Ding, A. (2010). Nonresolving inflammation. Cell, 140, 871–882.Google Scholar
Nusslock, R., & Miller, G. E. (2016). Early-life adversity and physical and emotional health across the lifespan: A neuroimmune network hypothesis. Biological Psychiatry, 80, 23–32.Google Scholar
Poulton, R., Caspi, A., Milne, B. J., Thomson, W. M., Taylor, A., Sears, M. R., et al. (2002). Association between children's experience of socioeconomic disadvantage and adult health: A life-course study. Lancet, 360, 1640–1645.Google Scholar
Raison, C. L., & Miller, A. H. (2003). When not enough is too much: The role of insufficient glucocorticoid signaling in the pathophysiology of stress-related disorders. American Journal of Psychiatry, 160, 1554–1565.Google Scholar
Raudenbush, S. W. (2001). Toward a coherent framework for comparing trajectories of individual change. In Collins, L. M. & Sayer, A. G. (Eds.), New methods for the analysis of change: Decade of behavior (pp. 35–64). Washington, DC: APA.Google Scholar
Repetti, R. L., Robles, T. F., & Reynolds, B. R. (2011). Allostatic processes in the family. Development and Psychopathology, 23, 921–938.Google Scholar
Repetti, R. L., Taylor, S. E., & Seeman, T. E. (2002). Risky families: Family social environments and the mental and physical health of offspring. Psychological Bulletin, 128, 330–366.CrossRefGoogle ScholarPubMed
Ridker, P. M. (2007). Inflammatory biomarkers and risks of myocardial infarction, stroke, diabetes, and total mortality: Implications for longevity. Nutrition Reviews, 65, S253–S259.CrossRefGoogle ScholarPubMed
Rivest, S. (2010). Chapter 4—Interactions between the immune and neuroendocrine systems. Progress in Brain Research, 181, 43–53.Google Scholar
Ross, N. A., Wolfson, M. C., Dunn, J. R., Berthelot, J., Kaplan, G. A., & Lynch, J. W. (2000). Relation between income inequality and mortality in Canada and in the United States: Cross sectional assessment using census data and vital statistics. British Medical Journal, 320, 898–902.Google Scholar
Rudolph, K. D., & Hammen, C. (1999). Age and gender as determinants of stress exposure, generation, and reactions in youngsters: A transactional perspective. Child Development, 70, 660–677.Google Scholar
Schreier, H. M. C., Roy, L. B., Frimer, L. T., & Chen, E. (2014). Family chaos and adolescent inflammatory profiles: The moderating role of socioeconomic status. Psychosomatic Medicine, 76, 460–467.Google Scholar
Shih, J. H., Eberhart, N. K., Hammen, C. L., & Brennan, P. A. (2006). Differential exposure and reactivity to interpersonal stress predict sex differences in adolescent depression. Journal of Clinical Child and Adolescent Psychology, 35, 103–115.Google Scholar
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. Journal of the American Medical Association, 301, 2252–2259.CrossRefGoogle ScholarPubMed
Shonkoff, J. P., Garner, A. S., The Committee on Psychosocial Aspects of Child and Family Health, Committee on Early Childhood, Adoption, and Dependent Care, and Section on Developmental and Behavioral Pediatrics, Siegel, B. S., et al. (2012). The lifelong effects of early childhood adversity and toxic stress. Pediatrics, 129, e232–e246.Google Scholar
Slavich, G. M., & Irwin, M. R. (2014). From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. Psychological Bulletin, 140, 774–815.Google Scholar
Smetana, J. G., Campione-Barr, N., & Metzger, A. (2006). Adolescent development in interpersonal and societal contexts. Annual Review of Psychology, 57, 255–284.Google Scholar
Tolan, P. H. (2016). Community violence exposure and developmental psychopathology. In Cicchetti, D. (Ed.), Developmental psychopathology (3rd ed., Vol. 4, pp. 43–85). Hoboken, NJ: Wiley.Google Scholar
Weiss, B., Dodge, K. A., Bates, J. E., & Pettit, G. S. (1992). Some consequences of early harsh discipline: Child aggression and a maladaptive social information processing style. Child Development, 63, 1321–1335.Google Scholar
West, S. G., Ryu, E., Kwok, O. M., & Cham, H. (2011). Multilevel modeling: Current and future applications in personality research. Journal of Personality, 79, 2–50.Google Scholar
Yeh, E. T. H., & Willerson, J. T. (2003). Coming of age of C-reactive protein: Using inflammation markers in cardiology. Circulation, 107, 370–371.Google Scholar
Zhang, X., & Mosser, D. M. (2008). Macrophage activation by endogenous danger signals. Journal of Pathology, 214, 161–178.CrossRefGoogle ScholarPubMed
Zunszain, P. A., Hepgul, N., & Pariante, C. M. (2013). Inflammation and depression. In Cohen, P. J., Sharp, T., & Lau, J. Y. F. (Eds.), Behavioral neurobiology of depression and its treatment (pp. 135–151). New York: Springer.Google Scholar