{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:54:56Z","timestamp":1791996896272,"version":"4.4.0"},"reference-count":88,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T00:00:00Z","timestamp":1625184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1078928"],"award-info":[{"award-number":["1078928"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Recent reports suggest a link between positive regulation of the Hippo pathway with bipolar disorder (BD), and the Hippo pathway is known to interact with multiple other signaling pathways previously associated with BD and other psychiatric disorders. In this study, neuronal-like NT2 cells were treated with amisulpride (10 \u00b5M), aripiprazole (0.1 \u00b5M), clozapine (10 \u00b5M), lamotrigine (50 \u00b5M), lithium (2.5 mM), quetiapine (50 \u00b5M), risperidone (0.1 \u00b5M), valproate (0.5 mM), or vehicle control for 24 h. Genome-wide mRNA expression was quantified and analyzed using gene set enrichment analysis (GSEA), with genes belonging to Hippo, Wnt, Notch, TGF- \u03b2, and Hedgehog retrieved from the KEGG database. Five of the eight drugs downregulated the genes of the Hippo pathway and modulated several genes involved in the interacting pathways. We speculate that the regulation of these genes, especially by aripiprazole, clozapine, and quetiapine, results in a reduction of MAPK and NF\u03baB pro-inflammatory signaling through modulation of Hippo, Wnt, and TGF-\u03b2 pathways. We also employed connectivity map analysis to identify compounds that act on these pathways in a similar manner to the known psychiatric drugs. Thirty-six compounds were identified. The presence of antidepressants and antipsychotics validates our approach and reveals possible new targets for drug repurposing.<\/jats:p>","DOI":"10.3390\/ijms22137164","type":"journal-article","created":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T10:06:34Z","timestamp":1625220394000},"page":"7164","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Transcriptional Modulation of the Hippo Signaling Pathway by Drugs Used to Treat Bipolar Disorder and Schizophrenia"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8825-734X","authenticated-orcid":false,"given":"Bruna","family":"Panizzutti","sequence":"first","affiliation":[{"name":"Institute for Innovation in Physical and Mental Health and Clinical Translation, School of Medicine, Deakin University, IMPACT, Geelong 3220, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara C.","family":"Bortolasci","sequence":"additional","affiliation":[{"name":"Institute for Innovation in Physical and Mental Health and Clinical Translation, School of Medicine, Deakin University, IMPACT, Geelong 3220, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Briana","family":"Spolding","sequence":"additional","affiliation":[{"name":"Institute for Innovation in Physical and Mental Health and Clinical Translation, School of Medicine, Deakin University, IMPACT, Geelong 3220, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srisaiyini","family":"Kidnapillai","sequence":"additional","affiliation":[{"name":"Institute for Innovation in Physical and Mental Health and Clinical Translation, School of Medicine, Deakin University, IMPACT, Geelong 3220, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Connor","sequence":"additional","affiliation":[{"name":"Institute for Innovation in Physical and Mental Health and Clinical Translation, School of Medicine, Deakin University, IMPACT, Geelong 3220, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark F.","family":"Richardson","sequence":"additional","affiliation":[{"name":"Genomics Centre, School of Life and Environmental Sciences, Deakin University, Burwood 3125, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9301-5911","authenticated-orcid":false,"given":"Trang T. T.","family":"Truong","sequence":"additional","affiliation":[{"name":"Institute for Innovation in Physical and Mental Health and Clinical Translation, School of Medicine, Deakin University, IMPACT, Geelong 3220, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe S. J.","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute for Innovation in Physical and Mental Health and Clinical Translation, School of Medicine, Deakin University, IMPACT, Geelong 3220, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerwyn","family":"Morris","sequence":"additional","affiliation":[{"name":"Institute for Innovation in Physical and Mental Health and Clinical Translation, School of Medicine, Deakin University, IMPACT, Geelong 3220, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Gray","sequence":"additional","affiliation":[{"name":"Institute for Innovation in Physical and Mental Health and Clinical Translation, School of Medicine, Deakin University, IMPACT, Geelong 3220, Australia"},{"name":"Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1299-4300","authenticated-orcid":false,"given":"Jee","family":"Hyun Kim","sequence":"additional","affiliation":[{"name":"Institute for Innovation in Physical and Mental Health and Clinical Translation, School of Medicine, Deakin University, IMPACT, Geelong 3220, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2776-3935","authenticated-orcid":false,"given":"Olivia M.","family":"Dean","sequence":"additional","affiliation":[{"name":"Institute for Innovation in Physical and Mental Health and Clinical Translation, School of Medicine, Deakin University, IMPACT, Geelong 3220, Australia"},{"name":"Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5554-6946","authenticated-orcid":false,"given":"Michael","family":"Berk","sequence":"additional","affiliation":[{"name":"Institute for Innovation in Physical and Mental Health and Clinical Translation, School of Medicine, Deakin University, IMPACT, Geelong 3220, Australia"},{"name":"Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville 3052, Australia"},{"name":"Department of Psychiatry, Royal Melbourne Hospital, University of Melbourne, Parkville 3052, Australia"},{"name":"Centre of Youth Mental Health, University of Melbourne, Parkville 3052, Australia"},{"name":"Orygen Youth Health Research Centre, Parkville 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6758-4763","authenticated-orcid":false,"given":"Ken","family":"Walder","sequence":"additional","affiliation":[{"name":"Institute for Innovation in Physical and Mental Health and Clinical Translation, School of Medicine, Deakin University, IMPACT, Geelong 3220, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1146\/annurev-biochem-013118-111829","article-title":"The Hippo Pathway: Biology and Pathophysiology","volume":"88","author":"Ma","year":"2019","journal-title":"Annu. 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