{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:59:08Z","timestamp":1790009948827,"version":"4.0.1"},"reference-count":70,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001675","name":"International Brain Research Organization","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001675","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["U01 DA043098"],"award-info":[{"award-number":["U01 DA043098"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006346","name":"Hope for Depression Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006346","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Early life stress (ELS) refers to exposure to negative childhood experiences, such as neglect, disaster, and physical, mental, or emotional abuse. ELS can permanently alter the brain, leading to cognitive impairment, increased sensitivity to future stressors, and mental health risks. The prefrontal cortex (PFC) is a key brain region implicated in the effects of ELS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To better understand the effects of ELS on the PFC, we ran a meta\u2010analysis of publicly available transcriptional profiling datasets. We identified five datasets (GSE89692, GSE116416, GSE14720, GSE153043, and GSE124387) that characterized the long\u2010term effects of multiday postnatal ELS paradigms (maternal separation, limited nesting\/bedding) in male and female laboratory rodents (rats, mice). The outcome variable was gene expression in the PFC later in adulthood as measured by microarray or RNA\u2010Seq. To conduct the meta\u2010analysis, preprocessed gene expression data were extracted from the Gemma database. Following quality control, the final sample size was\n                      <jats:italic>n<\/jats:italic>\n                      = 89\n                      <jats:italic>(n<\/jats:italic>\n                      = 42 controls and\n                      <jats:italic>n<\/jats:italic>\n                      = 47 ELS: GSE116416,\n                      <jats:italic>n<\/jats:italic>\n                      = 23 (no outliers); GSE116416,\n                      <jats:italic>n<\/jats:italic>\n                      = 44 (two outliers); GSE14720,\n                      <jats:italic>n<\/jats:italic>\n                      = 7 (no outliers); GSE153043,\n                      <jats:italic>n<\/jats:italic>\n                      = 9 (one outlier); and GSE124387,\n                      <jats:italic>n<\/jats:italic>\n                      = 6 (no outliers)). Differential expression was calculated using the\n                      <jats:italic>limma<\/jats:italic>\n                      pipeline followed by an empirical Bayes correction. For each gene, a random\u2010effects meta\u2010analysis model was then fit to the ELS versus control effect sizes (Log2 Fold Changes) from each study.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our meta\u2010analysis yielded stable estimates for 11,885 genes, identifying five genes with differential expression following ELS (false discovery rate &lt; 0.05) \u2014 transforming growth factor alpha (\n                      <jats:italic>Tgfa<\/jats:italic>\n                      ), IQ motif containing GTPase activating protein 3 (\n                      <jats:italic>Iqgap3<\/jats:italic>\n                      ), collagen, type XI, alpha 1 (\n                      <jats:italic>Col11a1<\/jats:italic>\n                      ), claudin 11 (\n                      <jats:italic>Cldn11<\/jats:italic>\n                      ), and myelin\u2010associated glycoprotein (\n                      <jats:italic>Mag<\/jats:italic>\n                      ) \u2014 all of which were downregulated. Broadly, gene sets associated with oligodendrocyte differentiation, myelination, and brain development were downregulated following ELS. In contrast, genes previously shown to be upregulated in major depressive disorder patients were upregulated following ELS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest that ELS during critical periods of development may produce long\u2010term effects on the efficiency of transmission in the PFC and drive changes in gene expression similar to those underlying depression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.70608","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T03:49:22Z","timestamp":1750132162000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Meta\u2010Analysis of the Effects of Early Life Stress on the Prefrontal Cortex Transcriptome Reveals Long\u2010Term Downregulation of Myelin\u2010Related Gene Expression"],"prefix":"10.1002","volume":"15","author":[{"given":"Toni Q.","family":"Duan","sequence":"first","affiliation":[{"name":"Grinnell College  Grinnell Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3715-9475","authenticated-orcid":false,"given":"Megan H.","family":"Hagenauer","sequence":"additional","affiliation":[{"name":"Michigan Neuroscience Institute University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth I.","family":"Flandreau","sequence":"additional","affiliation":[{"name":"Psychology Department Grand Valley State University  Allendale Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Bader","sequence":"additional","affiliation":[{"name":"Grinnell College  Grinnell Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duy Manh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Grinnell College  Grinnell Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela M.","family":"Maras","sequence":"additional","affiliation":[{"name":"Michigan Neuroscience Institute University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randriely Merscher S. 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