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The microarray profiling study underscored<jats:italic>JAG1<\/jats:italic>as the most promising candidate. Combined with further validation with real-time PCR, downregulation of<jats:italic>NOTCH1<\/jats:italic>was statistically significant. Accordingly, we reverse-translated the significant finding from a surrogate tissue for neurons, and studied the behavioral profile of<jats:italic>Notch1<\/jats:italic><jats:sup><jats:italic>+\/<\/jats:italic>\u2212<\/jats:sup>mice. We found a specific impairment in social novelty recognition, whereas other behaviors, such as sociability, novel object recognition and olfaction of social odors, were normal. This social novelty recognition deficit was male-specific and was rescued by rapamycin treatment. Based on the results from the animal model, we next tested whether patients with psychosis might have male-specific alterations in social cognition in association with the expression of<jats:italic>NOTCH1<\/jats:italic>or<jats:italic>JAG1<\/jats:italic>. In our first episode psychosis cohort, we observed a specific correlation between the expression of<jats:italic>JAG1<\/jats:italic>and a face processing measure only in male patients. The expression of<jats:italic>JAG1<\/jats:italic>was not correlated with any other cognitive and symptomatic scales in all subjects. Together, although we acknowledge the pioneering and exploratory nature, the present work that combines both human and animal studies in a reciprocal manner suggests a novel role for the Notch\u2013JAG pathway in a behavioral dimension(s) related to social cognition in psychotic disorders in a male-specific manner.<\/jats:p>","DOI":"10.1038\/s41398-022-01867-4","type":"journal-article","created":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T18:02:31Z","timestamp":1646935351000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Sex-specific involvement of the Notch\u2013JAG pathway in social recognition"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8950-391X","authenticated-orcid":false,"given":"Hanna","family":"Jaaro-Peled","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa A.","family":"Landek-Salgado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola G.","family":"Cascella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Frederick C.","family":"Nucifora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2514-9640","authenticated-orcid":false,"given":"Jennifer M.","family":"Coughlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"Nestadt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas W.","family":"Sedlak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joelle","family":"Lavoie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"De Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsunori","family":"Tajinda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8823-4324","authenticated-orcid":false,"given":"Hideki","family":"Hiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koko","family":"Ishizuka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1401-3008","authenticated-orcid":false,"given":"Akira","family":"Sawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,10]]},"reference":[{"key":"1867_CR1","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1038\/nn.4267","volume":"19","author":"T Singh","year":"2016","unstructured":"Singh T, Kurki MI, Curtis D, Purcell SM, Crooks L, McRae J, et al. 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