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However, several case reports have indicated treatment with lurasidone\u2010induced acute mania in people with bipolar depression. The mechanism by which this occurs remains to be elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>In this study, we systematically explored the mechanism of action of lurasidone\u2010induced acute mania in bipolar depression using network pharmacology and molecular docking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Putative target genes for lurasidone were obtained from the GeneCards, PharmMapper, SwissTargetPrediction, and DrugBank databases. Targets for bipolar depression and acute mania were collected from the DisGeNET and GeneCards databases. A protein\u2013protein interaction (PPI) network was built to screen the hub targets. The Bioinformatics platform and Database for Annotation, Visualization, and Integrated Discovery were used for the visualization of the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of the top 20 core targets. The drug\u2010pathway\u2010target\u2010disease network was constructed using Cytoscape. Finally, molecular docking was performed to evaluate the binding affinity between lurasidone and potential targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In total, 327, 1253, and 429 targets of lurasidone, bipolar depression, and acute mania were identified, respectively. A topological analysis of the PPI network revealed the top 20 hub targets. Based on PPI, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the top 20 hub targets, lurasidone was found to induce acute manic episodes in people with bipolar depression by targeting the serotonergic synapse signaling pathway via MAOB, HTR1A, HTR2A, HTR3A, SLC18A2, HTR1B, and HTR7. Molecular docking revealed good binding affinities between lurasidone and these potential targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study revealed that lurasidone may regulate the serotonergic synapse signaling pathway by interacting with the identified core targets MAOB, HTR1A, HTR2A, HTR3A, SLC18A2, HTR1B, and HTR7 to induce treatment\u2010emergent mania in people with bipolar depression. Our work provides a theoretical basis for the pharmacology of lurasidone\u2010induced acute mania in bipolar depression and further basic research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70383","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T12:23:23Z","timestamp":1744201403000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Characterization of the Molecular Mechanisms Underlying Lurasidone\u2010Induced Acute Manic Episodes in Bipolar Depression: A Network Pharmacology and Molecular Docking Approach"],"prefix":"10.1111","volume":"31","author":[{"given":"Chao","family":"Li","sequence":"first","affiliation":[{"name":"Computational Biology and Animal Imaging Center (CBAC) Tianjin Anding Hospital, Nankai University Affiliated Tianjin Anding Hospital, Tianjin Medical University Affiliated Tianjin Anding Hospital, Tianjin Medical University Affiliated Tianjin 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