{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:45:54Z","timestamp":1792017954204,"version":"4.4.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T00:00:00Z","timestamp":1673222400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T00:00:00Z","timestamp":1673222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Res"],"published-print":{"date-parts":[[2023,7]]},"DOI":"10.1038\/s41390-022-02441-w","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T15:12:31Z","timestamp":1673277151000},"page":"193-199","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Epigenetic differences in stress response gene FKBP5 among children with abusive vs accidental injuries"],"prefix":"10.1038","volume":"94","author":[{"given":"Todd M.","family":"Everson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Kaczor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathi","family":"Makoroff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Meyers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norell","family":"Rosado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Charleston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina","family":"Bertocci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Flores","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Lehnig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Clyde","family":"Pierce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,1,9]]},"reference":[{"key":"2441_CR1","doi-asserted-by":"publisher","first-page":"e1337","DOI":"10.1542\/peds.2015-0356","volume":"135","author":"CW Christian","year":"2015","unstructured":"Christian, C. W., Committee on Child Abuse and Neglect, American Academy of Pediatrics. The evaluation of suspected child physical abuse. Pediatrics 135, e1337\u2013e1354 (2015).","journal-title":"Pediatrics"},{"key":"2441_CR2","doi-asserted-by":"publisher","first-page":"e232","DOI":"10.1542\/peds.2011-2663","volume":"129","author":"JP Shonkoff","year":"2012","unstructured":"Shonkoff, J. P. & Garner, A. S. Committee on Psychosocial Aspects of Child and Family Health; Committee on Early Childhood, Adoption, and Dependent Care; Section on Developmental and Behavioral Pediatrics. The lifelong effects of early childhood adversity and toxic stress. Pediatrics 129, e232\u2013e246 (2012).","journal-title":"Pediatrics"},{"key":"2441_CR3","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1080\/15622975.2019.1583369","volume":"21","author":"J Nothling","year":"2020","unstructured":"Nothling, J., Malan-Muller, S., Abrahams, N., Hemmings, S. M. J. & Seedat, S. Epigenetic alterations associated with childhood trauma and adult mental health outcomes: a systematic review. World J. Biol. Psychiatry 21, 493\u2013512 (2020).","journal-title":"World J. Biol. Psychiatry"},{"key":"2441_CR4","doi-asserted-by":"publisher","first-page":"808","DOI":"10.3389\/fpsyt.2019.00808","volume":"10","author":"S Jiang","year":"2019","unstructured":"Jiang, S., Postovit, L., Cattaneo, A., Binder, E. B. & Aitchison, K. J. Epigenetic modifications in stress response genes associated with childhood trauma. Front. Psychiatry 10, 808 (2019).","journal-title":"Front. Psychiatry"},{"key":"2441_CR5","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-020-0846-2","volume":"10","author":"N Alexander","year":"2020","unstructured":"Alexander, N., Kirschbaum, C., Stalder, T., Muehlhan, M. & Vogel, S. No association between FKBP5 gene methylation and acute and long-term cortisol output. Transl. Psychiatry 10, 175 (2020).","journal-title":"Transl. Psychiatry"},{"key":"2441_CR6","doi-asserted-by":"publisher","first-page":"1895","DOI":"10.1017\/S095457941700147X","volume":"29","author":"MB Harms","year":"2017","unstructured":"Harms, M. B. et al. Early life stress, FK506 binding protein 5 gene (FKBP5) methylation, and inhibition-related prefrontal function: a prospective longitudinal study. Dev. Psychopathol. 29, 1895\u20131903 (2017).","journal-title":"Dev. Psychopathol."},{"key":"2441_CR7","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/nn.3275","volume":"16","author":"T Klengel","year":"2013","unstructured":"Klengel, T. et al. Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nat. Neurosc. 16, 33\u201341 (2013).","journal-title":"Nat. Neurosc."},{"key":"2441_CR8","doi-asserted-by":"publisher","first-page":"3792","DOI":"10.3390\/jcm9123792","volume":"9","author":"B Misiak","year":"2020","unstructured":"Misiak, B. et al. Adverse childhood experiences and methylation of the FKBP5 gene in patients with psychotic disorders. J. Clin. Med. 9, 3792 (2020).","journal-title":"J. Clin. Med."},{"key":"2441_CR9","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1038\/npp.2017.290","volume":"43","author":"L Tozzi","year":"2018","unstructured":"Tozzi, L. et al. Epigenetic changes of FKBP5 as a link connecting genetic and environmental risk factors with structural and functional brain changes in major depression. Neuropsychopharmacology 43, 1138\u20131145 (2018).","journal-title":"Neuropsychopharmacology"},{"key":"2441_CR10","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.jpsychires.2017.09.016","volume":"96","author":"AC Bustamante","year":"2018","unstructured":"Bustamante, A. C. et al. FKBP5 DNA methylation does not mediate the association between childhood maltreatment and depression symptom severity in the Detroit Neighborhood Health Study. J. Psychiatr. Res. 96, 39\u201348 (2018).","journal-title":"J. Psychiatr. Res."},{"key":"2441_CR11","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/j.psychres.2018.04.064","volume":"265","author":"C Farrell","year":"2018","unstructured":"Farrell, C. et al. DNA methylation differences at the glucocorticoid receptor gene in depression are related to functional alterations in hypothalamic-pituitary-adrenal axis activity and to early life emotional abuse. Psychiatry Res. 265, 341\u2013348 (2018).","journal-title":"Psychiatry Res."},{"key":"2441_CR12","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1038\/s41386-019-0319-6","volume":"44","author":"J Klinger-Konig","year":"2019","unstructured":"Klinger-Konig, J. et al. Methylation of the FKBP5 gene in association with FKBP5 genotypes, childhood maltreatment and depression. Neuropsychopharmacology 44, 930\u2013938 (2019).","journal-title":"Neuropsychopharmacology"},{"key":"2441_CR13","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1111\/gbb.12342","volume":"16","author":"S Yeo","year":"2017","unstructured":"Yeo, S. et al. The influence of FKBP5 genotype on expression of FKBP5 and other glucocorticoid-regulated genes, dependent on trauma exposure. Genes Brain Behav. 16, 223\u2013232 (2017).","journal-title":"Genes Brain Behav."},{"key":"2441_CR14","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0503-2","volume":"15","author":"JP Fortin","year":"2014","unstructured":"Fortin, J. P. et al. Functional normalization of 450k methylation array data improves replication in large cancer studies. Genome Biol. 15, 503 (2014).","journal-title":"Genome Biol."},{"key":"2441_CR15","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-1066-1","volume":"17","author":"R Pidsley","year":"2016","unstructured":"Pidsley, R. et al. Critical evaluation of the Illumina MethylationEPIC BeadChip microarray for whole-genome DNA methylation profiling. Genome Biol. 17, 208 (2016).","journal-title":"Genome Biol."},{"key":"2441_CR16","doi-asserted-by":"publisher","first-page":"925","DOI":"10.2217\/epi-2018-0037","volume":"10","author":"SC Zheng","year":"2018","unstructured":"Zheng, S. C. et al. A novel cell-type deconvolution algorithm reveals substantial contamination by immune cells in saliva, buccal and cervix. Epigenomics 10, 925\u2013940 (2018).","journal-title":"Epigenomics"},{"key":"2441_CR17","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1093\/bioinformatics\/bts034","volume":"28","author":"JT Leek","year":"2012","unstructured":"Leek, J. T., Johnson, W. E., Parker, H. S., Jaffe, A. E. & Storey, J. D. The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics 28, 882\u2013883 (2012).","journal-title":"Bioinformatics"},{"key":"2441_CR18","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1101\/gr.229102","volume":"12","author":"WJ Kent","year":"2002","unstructured":"Kent, W. J. et al. The human genome browser at UCSC. Genome Res. 12, 996\u20131006 (2002).","journal-title":"Genome Res."},{"key":"2441_CR19","doi-asserted-by":"crossref","unstructured":"Fishilevich, S., et al. GeneHancer: genome-wide integration of enhancers and target genes in GeneCards. Database (Oxford) 2017, bax028 (2017).","DOI":"10.1093\/database\/bax028"},{"key":"2441_CR20","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-019-0376-y","volume":"9","author":"PR Braun","year":"2019","unstructured":"Braun, P. R. et al. Genome-wide DNA methylation comparison between live human brain and peripheral tissues within individuals. Transl. Psychiatry 9, 47 (2019).","journal-title":"Transl. Psychiatry"},{"key":"2441_CR21","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1017\/S0954579417001286","volume":"29","author":"SH Parade","year":"2017","unstructured":"Parade, S. H. et al. Change in FK506 binding protein 5 (FKBP5) methylation over time among preschoolers with adversity. Dev. Psychopathol. 29, 1627\u20131634 (2017).","journal-title":"Dev. Psychopathol."},{"key":"2441_CR22","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.jaac.2013.12.025","volume":"53","author":"N Weder","year":"2014","unstructured":"Weder, N. et al. Child abuse, depression, and methylation in genes involved with stress, neural plasticity, and brain circuitry. J. Am. Acad. Child Adolesc. Psychiatry 53, 417\u2013424.e5 (2014).","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"2441_CR23","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1210\/me.2009-0443","volume":"24","author":"V Paakinaho","year":"2010","unstructured":"Paakinaho, V., Makkonen, H., Jaaskelainen, T. & Palvimo, J. J. Glucocorticoid receptor activates poised FKBP51 locus through long-distance interactions. Mol. Endocrinol. 24, 511\u2013525 (2010).","journal-title":"Mol. Endocrinol."},{"key":"2441_CR24","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1038\/nrg3230","volume":"13","author":"PA Jones","year":"2012","unstructured":"Jones, P. A. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat. Rev. Genet. 13, 484\u2013492 (2012).","journal-title":"Nat. Rev. Genet."},{"key":"2441_CR25","doi-asserted-by":"publisher","first-page":"11370","DOI":"10.1073\/pnas.1816847116","volume":"116","author":"AS Zannas","year":"2019","unstructured":"Zannas, A. S. et al. Epigenetic upregulation of FKBP5 by aging and stress contributes to NF-\u03baB-driven inflammation and cardiovascular risk. Proc. Natl Acad. Sci. Usa. 116, 11370\u201311379 (2019).","journal-title":"Proc. Natl Acad. Sci. Usa."},{"key":"2441_CR26","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1136\/annrheumdis-2022-222156","volume":"81","author":"E Estupi\u00f1\u00e1n-Moreno","year":"2022","unstructured":"Estupi\u00f1\u00e1n-Moreno, E. et al. Methylome and transcriptome profiling of giant cell arteritis monocytes reveals novel pathways involved in disease pathogenesis and molecular response to glucocorticoids. Ann. Rheum. Dis. 81, 1290\u20131300 (2022).","journal-title":"Ann. Rheum. Dis."},{"key":"2441_CR27","doi-asserted-by":"publisher","first-page":"4609","DOI":"10.1074\/jbc.M407498200","volume":"280","author":"GM Wochnik","year":"2005","unstructured":"Wochnik, G. M. et al. FK506-binding proteins 51 and 52 differentially regulate dynein interaction and nuclear translocation of the glucocorticoid receptor in mammalian cells. J. Biol. Chem. 280, 4609\u20134616 (2005).","journal-title":"J. Biol. Chem."},{"key":"2441_CR28","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1111\/pcn.12835","volume":"73","author":"PR Braun","year":"2019","unstructured":"Braun, P. R. et al. Genome-wide DNA methylation investigation of glucocorticoid exposure within buccal samples. Psychiatry Clin. Neurosci. 73, 323\u2013330 (2019).","journal-title":"Psychiatry Clin. Neurosci."},{"key":"2441_CR29","doi-asserted-by":"publisher","DOI":"10.1038\/srep44445","volume":"7","author":"C Glad","year":"2017","unstructured":"Glad, C. et al. Reduced DNA methylation and psychopathology following endogenous hypercortisolism \u2013 a genome-wide study. Sci. Rep. 7, 44445 (2017).","journal-title":"Sci. Rep."},{"key":"2441_CR30","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1038\/npp.2015.235","volume":"41","author":"AS Zannas","year":"2016","unstructured":"Zannas, A. S., Wiechmann, T., Gassen, N. C. & Binder, E. B. Gene-stress-epigenetic regulation of FKBP5: clinical and translational implications. Neuropsychopharmacol 41, 261\u2013274 (2016).","journal-title":"Neuropsychopharmacol"},{"key":"2441_CR31","unstructured":"Matosin, N., et al. Brain expressed FKBP5 delineates a therapeutic subtype of severe mental illness. Preprint at bioRxiv (2021)."},{"key":"2441_CR32","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1002\/ajmg.b.32278","volume":"168B","author":"AK Smith","year":"2015","unstructured":"Smith, A. K. et al. DNA extracted from saliva for methylation studies of psychiatric traits: evidence tissue specificity and relatedness to brain. Am. J. Med. Genet. B: Neuropsychiatr. Genet. 168B, 36\u201344 (2015).","journal-title":"Am. J. Med. Genet. B: Neuropsychiatr. Genet."}],"container-title":["Pediatric Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41390-022-02441-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-022-02441-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-022-02441-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T18:43:14Z","timestamp":1689792194000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41390-022-02441-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,9]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["2441"],"URL":"https:\/\/doi.org\/10.1038\/s41390-022-02441-w","relation":{},"ISSN":["0031-3998","1530-0447"],"issn-type":[{"value":"0031-3998","type":"print"},{"value":"1530-0447","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,9]]},"assertion":[{"value":"24 March 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 November 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 December 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 January 2023","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"For patients undergoing abuse evaluations, a waiver of authorization was granted to avoid interference with the evaluation process. For patients not undergoing an abuse evaluation, informed consent was obtained from legal guardians. This study was reviewed and approved by both Lurie Children\u2019s Hospital and Cincinnati Children\u2019s Hospital Institutional Review Boards (IRBs).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}]}}