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Adverse childhood experiences and transcriptional response in school-age children

Published online by Cambridge University Press:  28 January 2021

A. Marie-Mitchell Open the ORCID record for A. Marie-Mitchell [Opens in a new window]  and
S.W. Cole
A. Marie-Mitchell*
Affiliation:
Preventive Medicine & Pediatrics Departments, Loma Linda University, Loma Linda, CA, USA
S.W. Cole
Affiliation:
Department of Psychiatry and Behavioral Sciences & Department of Medicine, Division of Hematology-Oncology, UCLA School of Medicine, Los Angeles, CA, USA
*
Author for Correspondence: Ariane Marie-Mitchell, 24785 Stewart St, Suite 206, Loma Linda, CA92354, USA; E-mail [email protected]
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Abstract

This study evaluated whether children with higher adverse childhood experiences (ACE) scores had alterations in immune cell gene expression profiles. RNA sequencing was conducted on dried blood spot samples from 37 generally healthy English-speaking children (age 5–11) who were recruited from well-child visits at a university-affiliated pediatric practice. The Whole Child Assessment was used to assess ACE exposure. Primary analyses examined an a priori-specified composite of 19 pro-inflammatory gene transcripts. Secondary analyses examined a 34-gene composite assessing Type I interferon response, and used Transcript Origin Analyses to identify cellular mechanisms. After controlling for age, body mass index percentile, sex, race/ethnicity, current insurance status, and household smoking exposure, pro-inflammatory gene expression was elevated by 0.094 log2 RNA expression units with each Child-ACE total score point (p = .019). Type I interferon gene expression was similarly upregulated (0.103; p = .008). Transcript origin analyses implicated CD8+ T cell as the primary sources of gene transcripts upregulated, and nonclassical (CD16+) monocytes as sources of downregulated transcripts. These preliminary analyses suggest that parent-reported ACE exposures are associated with increased expression of both inflammatory and interferon gene transcripts in children's circulating blood cells.

Keywords

adverse childhood experiencesadversitybiomarkersimmunologyinflammation
Type
Regular Article
Information
Development and Psychopathology , Volume 34 , Issue 3 , August 2022 , pp. 875 - 881
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Copyright
© The Author(s), 2021. Published by Cambridge University Press

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References

Adamao, S. (2014). The effects of stress hormones on immune function may be vital for the adaptive reconfiguration of the immune system during fight-or-flight behavior. Integrative and Comparative Biology, 54, 419–426. doi:10.1093/icb/icu005CrossRefGoogle Scholar
Anda, R., Felitti, V., Bremner, J., Walker, J., Whitfield, C., Perry, B., … Giles, W. (2006). The enduring effects of abuse and related adverse experiences in childhood. A convergence of evidence from neurobiology and epidemiology. European Archives of Psychiatry and Clinical Neuroscience, 256, 174–186.CrossRefGoogle ScholarPubMed
Antoni, M., Bouchard, L., Jacobs, J., Lechner, S., Jutagir, D., Gudenkauf, L., … Blomberg, B. (2016). Stress management, leukocyte transcriptional changes and breast cancer recurrence in a randomized trial: An exploratory analysis. Psychoneuroendocrinology, 74, 269–277.CrossRefGoogle Scholar
Black, D., Cole, S., Christodoulou, G., & Figueiredo, J. (2018). Genomic mechanisms of fatigue in survivors of colorectal cancer. Cancer, 124, 2637–2644. doi:10.1002/cncr.31356CrossRefGoogle ScholarPubMed
Brown, D., Anda, R., Tiemeier, H., Felitti, V., Edwards, V., Croft, J., & Giles, W. (2009). Adverse childhood experiences and the risk of premature mortality. American Journal of Preventive Medicine, 37, 389–396.CrossRefGoogle ScholarPubMed
Carsetti, R., Quintarelli, C., Quinti, I., Mortari, E., Zumla, A., Ippolito, G., & Locatelli, F. (2020). The immune system of children: The key to understanding SARS-CoV-2 susceptibility? Lancet Child & Adolescent Health, 4, 414–416.CrossRefGoogle ScholarPubMed
Centers for Disease Control and Prevention, & National Center for Chronic Disease Prevention and Health Promotion. (2009). The Power of Prevention: Chronic Disease…The Public Health Challenge of The 21st Century. Retrieved from Atlanta, GA.Google Scholar
Chiang, J. J., Ko, A., Bower, J. E., Taylor, S. E., Irwin, M. R., & Fuligni, A. J. (2019). Stress, psychological resources, and HPA and inflammatory reactivity during late adolescence. Development and Psychopathology, 31, 699–712. doi:10.1017/s0954579418000287CrossRefGoogle ScholarPubMed
Chiang, J. J., Taylor, S. E., & Bower, J. E. (2015). Early adversity, neural development, and inflammation. Developmental Psychobiology, 57, 887–907. doi:10.1002/dev.21329CrossRefGoogle ScholarPubMed
Cicchetti, D., Handley, E. D., & Rogosch, F. A. (2015). Child maltreatment, inflammation, and internalizing symptoms: Investigating the roles of C-reactive protein, gene variation, and neuroendocrine regulation. Development and Psychopathology, 27, 553–566. doi:10.1017/s0954579415000152CrossRefGoogle ScholarPubMed
Cole, S. (2013). Social regulation of human gene expression: Mechanisms and implications for public Health. American Journal of Public Health, 103, S84–S92.CrossRefGoogle ScholarPubMed
Cole, S. (2014). Human social genomics. PLOS Genetics, 10, e1004601.CrossRefGoogle ScholarPubMed
Cole, S. (2019). The conserved transcriptional response to adversity. Current Opinion in Behavioral Sciences, 28, 31–37.CrossRefGoogle ScholarPubMed
Cole, S.W., Hawkley, L.C., Arevalo, J. M., & Cacioppo, J. T. (2011). Transcript origin analysis identifies antigen-presenting cells as primary targets of socially regulated gene expression in leukocytes. Proceedings of the National Academy of Sciences of the United States of America, 108, 3080–3085. doi:10.1073/pnas.1014218108CrossRefGoogle Scholar
Danese, A., Moffitt, T., Harrington, H., Milne, B., Polanczyk, G., Pariante, C., … 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 and Adolescent Medicine, 163, 1135–1143.CrossRefGoogle ScholarPubMed
Danese, A., Pariante, C., Caspi, A., Taylor, A., & Poulton, R. (2007). Childhood maltreatment predicts adult inflammation in a life-course study. Proceedings of the National Academy of Sciences of the United States of America, 104, 1319–1324.CrossRefGoogle Scholar
David, J., Measelle, J., Ostlund, B., & Ablow, J. (2017). Association between early life adversity and inflammation during infancy. Developmental Psychobiology, 59, 696–702. doi:10.1002/dev.21538CrossRefGoogle ScholarPubMed
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., … Gingeras, T. R. (2013). STAR: Ultrafast universal RNA-seq aligner. Bioinformatics, 29, 15–21.CrossRefGoogle ScholarPubMed
Dubowitz, H., Lane, W., Semiatin, J., & Magder, L. (2012). The SEEK model of pediatric primary care: Can child maltreatment be prevented in a low-risk population? Academic Pediatrics, 12, 259–268.CrossRefGoogle Scholar
Ehrlich, K., Miller, G., & Chen, E. (2015). Harsh parent–child conflict is associated with decreased anti-inflammatory gene expression and increased symptom severity in children with asthma. Development and Psychopathology, 27, 1547–1554.CrossRefGoogle ScholarPubMed
Feigelman, S., Dubowitz, H., Lane, W., Grube, L., & Kim, J. (2011). Training pediatric residents in a primary care clinic to help address psychosocial problems and prevent child maltreatment. Academic Pediatrics, 11, 474–480. doi:10.1016/j.acap.2011.07.005CrossRefGoogle Scholar
Felitti, V. J., Anda, R. F., Nordenberg, D., Williamson, D. F., Spitz, A. M., Edwards, V., … Marks, J. S. (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.CrossRefGoogle ScholarPubMed
Gardner, W., Lucas, A., Kolko, D. J., & Campo, J. V. (2007). Comparison of the PSC-17 and alternative mental health screens in an at-risk primary care sample. Journal of the American Academy of Child & Adolescent Psychiatry, 46, 611–618.CrossRefGoogle Scholar
Howren, M., Lamkin, D., & Suls, J. (2009). Associations of depression with C-reactive protein, IL-1, and IL-6: A meta-analysis. Psychosomatic Medicine, 71, 171–186.CrossRefGoogle ScholarPubMed
Irwin, M., & Cole, S. (2011). Reciprocal regulation of the neural and innate immune systems. Nature Reviews Immunology, 11, 625–632. doi:10.1038/nri3042CrossRefGoogle ScholarPubMed
Jellinek, M., Murphy, J., Little, M., Pagano, M., Comer, D., & Kelleher, K. (1999). Use of the Pediatric Symptom Checklist (PSC) to screen for psychosocial problems in pediatric primary care: A national feasibility study. Archives of Pediatrics & Adolescent Medicine, 153, 254–260.CrossRefGoogle ScholarPubMed
Jiang, N. M., Tofail, F., Ma, J. Z., Haque, R., Kirkpatrick, B., Nelson, C. A., & Petri, W. A. (2017). Early life inflammation and neurodevelopmental outcome in Bangladeshi infants growing up in adversity. American Journal of Tropical Medicine and Hygiene, 97, 974–979. doi:10.4269/ajtmh.17-0083CrossRefGoogle ScholarPubMed
Knight, J., Rizzo, J., Logan, B., Wang, T., Arevalo, J., Ma, J., & Cole, S. (2016). Low Socioeconomic status, adverse gene expression profiles, and clinical outcomes in hematopoietic stem cell transplant recipients. Clinical Cancer Research, 22, 69–78. doi:10.1158/1078-0432.CCR-15-1344CrossRefGoogle ScholarPubMed
Knight, J., Rizzo, J., Wang, T., He, N., Logan, B., Spellman, S., … Cole, S. (2019). Molecular correlates of socioeconomic status and clinical outcomes following hematopoietic cell transplantation for leukemia. JNCI Cancer Spectrum, 3, pkz073. doi:10.1093/jncics/pkz073CrossRefGoogle ScholarPubMed
Kroenke, K., Spitzer, R., & Williams, J. (2003). The patient health questionnaire-2: Validity of a two-item depression screener. Medical Care, 41, 1284–1292.CrossRefGoogle ScholarPubMed
Kroenke, K., Spitzer, R., Williams, J., Monahan, P., & Löwe, B. (2007). Anxiety disorders in primary care: Prevalence, impairment, comorbidity, and detection. Annals of Internal Medicine, 146, 317–325.CrossRefGoogle ScholarPubMed
Marie-Mitchell, A., Lee, J., Siplon, C., Chan, F., Riesen, S., & Vercio, C. (2019). Implementation of the Whole Child Assessment to screen for adverse childhood experiences. Global Pediatric Health, 6, 1–9.CrossRefGoogle ScholarPubMed
Marie-Mitchell, A., Watkins, H., Copado, I., & Distelberg, B. (2020). Use of the Whole Child Assessment to identify children at risk of poor outcomes. Child Abuse and Neglect, 104, 104489. doi:10.1016/j.chiabu.2020.104489CrossRefGoogle ScholarPubMed
McDade, T., Williams, S., & Snodgrass, J. (2007). What a drop can do: Dried blood spots as a minimally invasive method for integratingbiomarkers into population-based research. Demography, 44, 899–925.CrossRefGoogle Scholar
Measelle, J., & Ablow, J. (2018). Contributions of early adversity to pro-inflammatory phenotype in infancy: The buffer provided by attachment security. Attachment & Human Development, 20, 1–23. doi:10.1080/14616734.2017.1362657CrossRefGoogle ScholarPubMed
Miller, G., & 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., Chen, E., & Cole, S. (2009). Health psychology: Developing biologically plausible models linking the social world and physical health. Annual Review of Psychology, 60, 501–524.CrossRefGoogle ScholarPubMed
Miller, G., Chen, E., Shalowitz, M., Story, R., Leigh, A., Ham, P., … Cole, S. (2018). Divergent transcriptional profiles in pediatric asthma patients of low and high socioeconomic status. Pediatric Pulmonology, 53, 710–719.CrossRefGoogle ScholarPubMed
Miller, G., & Cole, S. (2012). Clustering of depression and inflammation in adolescents previously exposed to childhood adversity. Biol Psychiatry, 72, 34–40. doi:10.1016/j.biopsych.2012.02.034CrossRefGoogle ScholarPubMed
Murphy, J., Reed, J., Jellinek, M., & Bishop, S. (1992). Screening for psychosocial dysfunction in inner-city children: Further validation of the pediatric symptom checklist. Journal of the American Academy of Child & Adolescent Psychiatry, 31, 1105–1111.CrossRefGoogle ScholarPubMed
Murphy, M., Slavich, G., Chen, E., & Miller, G. (2015). Targeted rejection predicts decreased anti-inflammatory gene expression and increased symptom severity in youth with asthma. Psychological Science, 26, 111–121.CrossRefGoogle ScholarPubMed
Murphy, M., Slavich, G., Rohleder, N., & Miller, G. (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.CrossRefGoogle ScholarPubMed
Repetti, R., Taylor, S., & Seeman, T. (2002). Risky families: Family social environments and the mental and physical health of offspring. Psychological Bulletin, 128, 330–366.CrossRefGoogle ScholarPubMed
Ross, K., Carroll, J., Dunkel Schetter, C., Hobel, C., & Cole, S. (2019). Pro-inflammatory immune cell gene expression during the third trimester of pregnancy is associated with shorter gestational length and lower birthweight. American Journal of Reproductive Immunology, 82, e13190. doi:10.1111/aji.13190CrossRefGoogle ScholarPubMed
Ross, K., Cole, S., Carroll, J., & Dunkel Schetter, C. (2019). Elevated pro-inflammatory gene expression in the third trimester of pregnancy in mothers who experienced stressful life events. Brain, Behavior and Immunity, 76, 97–103. doi:10.1016/j.bbi.2018.11.009CrossRefGoogle ScholarPubMed
Schwaiger, M., Grinberg, M., Moser, D., Zang, J., Heinrichs, M., Hengstler, J., … Kumsta, R. (2016). Altered stress-induced regulation of genes in monocytes in adults with a history of childhood adversity. Neuropsychopharmacology, 41, 2530–2540.CrossRefGoogle ScholarPubMed
Segerstrom, S., & Miller, G. (2004). Psychological Stress and the Human Immune System: A MetaAnalytic Study of 30 Years of Inquiry. Psychological Bulletin, 130, 601–630.CrossRefGoogle Scholar
Shonkoff, J., Garner, A., The Committee on Psychosocial Aspects of Child and Family Health, Committee on Early Childhood Adoption and Dependent Care, Section on Developmental and Behavioral Pediatrics, Siegel, B., . . . Wood, D. (2012). The lifelong effects of early childhood adversity and toxic stress. Pediatrics, 129, e232.CrossRefGoogle ScholarPubMed
Simons, R., Lei, M., Beach, S., Barr, A., Cutrona, C., Gibbons, F., & Philibert, R. (2017). An index of the ratio of inflammatory to antiviral cell types mediates the effects of social adversity and age on chronic illness. Social Science & Medicine, 185, 158–165.CrossRefGoogle ScholarPubMed
Slopen, N., Kubzansky, L. D., McLaughlin, K. A., & Koenen, K. C. (2013). Childhood adversity and inflammatory processes in youth: A prospective study. Psychoneuroendocrinology, 38, 188–200. doi:10.1016/j.psyneuen.2012.05.013CrossRefGoogle ScholarPubMed
Surtees, P., Wainwright, N., Day, N., Brayne, C., Luben, R., Khaw, K. T., … Khaw, K.-T. (2003). Adverse experience in childhood as a developmental risk factor for altered immune status in adulthood. International Journal of Behavioral Medicine, 10, 251–268.CrossRefGoogle ScholarPubMed
Taj, N., Devera-Sales, A., & Vinson, D. (1998). Screening for problem drinking: Does a single question work? Journal of Family Practice, 46, 328–335.Google ScholarPubMed
Trinchieri, G. (2010). Type I Interferon: Friend or foe? Journal of Experimental Medicine, 207, 2053–2063.CrossRefGoogle ScholarPubMed
Tyrka, A. R., Parade, S. H., Valentine, T. R., Eslinger, N. M., & Seifer, R. (2015). Adversity in preschool-aged children: Effects on salivary interleukin-1beta. Development and Psychopathology, 27, 567–576. doi:10.1017/s0954579415000164CrossRefGoogle ScholarPubMed
Wahadat, M., Bodewes, I., Maria, N., van Helden-Meeuwsen, C., van Dijk-Hummelman, A., Steenwijk, E., … Versnel, M. (2018). Type I IFN signature in childhood-onset systemic lupus erythematosus: A conspiracy of DNA- and RNA-sensing receptors? Arthritis Research & Therapy, 20), doi:10.1186/s13075-017-1501-zCrossRefGoogle ScholarPubMed
Zhoua, X., Fragalaa, M., McElhaney, J., & Kuchel, G. (2010). Conceptual and methodological issues relevant to cytokine and inflammatory marker measurements in clinical research. Current Opinion in Clinical Nutrition and Metabolic Care, 13, 541–547.CrossRefGoogle Scholar