{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:59:31Z","timestamp":1791561571404,"version":"4.3.4"},"reference-count":86,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"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\/100011555","name":"Grinnell College","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011555","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":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic stress is a major risk factor for psychiatric disorders, including anxiety, depression, and post\u2010traumatic stress disorder. Chronic stress can cause structural alterations like grey matter atrophy in key emotion\u2010related areas such as the prefrontal cortex (PFC). To identify biological pathways affected by chronic stress in the PFC, researchers have performed transcriptional profiling (RNA sequencing, microarray) to measure gene expression in rodent models. However, transcriptional signatures in the PFC that are shared across different chronic stress paradigms and laboratories remain relatively unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed a meta\u2010analysis of publicly available transcriptional profiling datasets within the\n                      <jats:italic>Gemma<\/jats:italic>\n                      database. We identified six datasets that characterized the effects of either chronic social defeat stress (CSDS) or chronic variable stress and\/or chronic unpredictable mild stress (CUMS) on gene expression in the PFC in mice (\n                      <jats:italic>n\u00a0<\/jats:italic>\n                      =\u00a0117). We fit a random effects meta\u2010analysis model to the chronic stress effect sizes (log(2) fold changes) for each transcript (\n                      <jats:italic>n\u00a0<\/jats:italic>\n                      =\u00a021,379) measured in most datasets. We then compared our results with two other published chronic stress meta\u2010analyses, as well as transcriptional signatures associated with psychiatric disorders.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified 133 genes that were consistently differentially expressed across chronic stress studies and paradigms (false discovery rate [FDR]\u00a0&lt;\u00a00.05). Fast gene set enrichment analysis (fGSEA) revealed 53 gene sets enriched with differential expression (FDR\u00a0&lt;\u00a00.05), dominated by glial and neurovascular markers (e.g., oligodendrocyte, astrocyte, endothelial\/vascular) and stress\u2010related signatures (e.g., major depressive disorder [MDD], hormonal responses). Immediate\u2010early gene markers of neuronal activity (\n                      <jats:italic>Fos, Junb, Arc, Dusp1<\/jats:italic>\n                      ) were consistently suppressed. Many of the identified effects resembled those seen in previous meta\u2010analyses characterizing stress effects (CSDS, early life stress), despite minimal overlap in included samples. Moreover, some effects resembled previous observations from psychiatric disorders, including alcohol abuse disorder, ma, bipolar disorder, and schizophrenia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study demonstrates that chronic stress induces a robust, cross\u2010paradigm PFC signature characterized by downregulation of glia\/myelin and vascular pathways and suppression of immediate\u2010early gene activity, highlighting cellular processes linking chronic stress exposure, PFC dysfunction, and psychiatric disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71197","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T07:23:25Z","timestamp":1769066605000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A Meta\u2010Analysis of the Effects of Chronic Stress on the Prefrontal Transcriptome in Animal Models and Convergence With Existing Human Data"],"prefix":"10.1002","volume":"16","author":[{"given":"Jinglin","family":"Xiong","sequence":"first","affiliation":[{"name":"Grinnell College  Grinnell Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":"Cosette A.","family":"Rhoads","sequence":"additional","affiliation":[{"name":"Grinnell College  Grinnell Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Flandreau","sequence":"additional","affiliation":[{"name":"Grand Valley State University  Allendale Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Rempel\u2010Clower","sequence":"additional","affiliation":[{"name":"Grinnell College  Grinnell Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Hernandez","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":"Annaka","family":"Saffron","sequence":"additional","affiliation":[{"name":"Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toni","family":"Duan","sequence":"additional","affiliation":[{"name":"Grinnell College  Grinnell Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Stanley","family":"Watson","sequence":"additional","affiliation":[{"name":"Michigan Neuroscience Institute University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huda","family":"Akil","sequence":"additional","affiliation":[{"name":"Michigan Neuroscience Institute University of Michigan  Ann Arbor Michigan 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