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This in silico study systematically investigated shared transcriptomic signatures and biological pathways using peripheral blood expression data. Differential expression analysis revealed 13 genes commonly dysregulated in at least two disorders, including CNTNAP3, PROK2, S100P, HLA\u2010DPB1, and IRAK3. Correlation patterns uncovered disorder\u2010specific rewiring of gene\u2013gene networks, with polarity shifts and strength alterations particularly involving EIF5A2 and CNTNAP3B in MDD and OCD. Functional enrichment revealed convergence in neurotransmission, synaptic regulation, immune signaling, and metabolic pathways. Five biological pathways, including \u201cdefense response to bacterium\u201d (GO\u2010BP), \u201ccytokine signaling in the immune system,\u201d \u201cTCR signaling,\u201d and \u201cneutrophil degranulation\u201d (Reactome), and \u201cleishmaniasis\u201d (KEGG), were enriched across all three disorders, alongside multiple overlaps in GO\u2010MF and GO\u2010CC domains. Protein\u2013protein interaction mapping revealed ribosomal hub dominance in OCD and immune\/inflammatory node centrality in MDD and GAD. A panel of 21 secreted dysregulated genes in MDD, validated for ELISA detection, demonstrated robust classification power (AUC &gt;\u20090.70). Drug\u2010gene interaction analysis identified four downregulated compounds, carbamazepine, flupirtine, indomethacin, and doxorubicin hydrochloride, shared across all three disorders, suggesting therapeutic repurposing potential. These findings highlight shared immunometabolic dysregulation and nominate blood\u2010based biomarkers and pharmacological targets applicable across psychiatric diagnostic categories.<\/jats:p>","DOI":"10.1002\/ajmg.b.70010","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T17:15:51Z","timestamp":1772990151000},"page":"349-374","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Shared Blood Transcriptomic and Pathway Signatures in Major Depression, Generalized Anxiety, and Obsessive\u2013Compulsive Disorder: A Systems\u2010Level Study"],"prefix":"10.1002","volume":"201","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6729-4697","authenticated-orcid":false,"given":"Niloufar","family":"Salimian","sequence":"first","affiliation":[{"name":"Department of Biology, Faculty of Basic Sciences Shahrekord Branch, Islamic Azad University  Shahrekord Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2012.00187"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2019-320912"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1193"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.13712"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00131746-200409000-00003"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.06.002"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.14m09029"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-022-00634-6"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0914005107"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2005.11.012"},{"key":"e_1_2_10_12_1","unstructured":"Breen M.\u201cBlood\u2010Based Biomarkers in Psychiatric Diseases\u201d(PhD diss. 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