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dc.contributor.authorHoseth, Eva Zsuzsanna
dc.contributor.authorKrull, Florian
dc.contributor.authorDieset, Ingrid
dc.contributor.authorMørch, Ragni Helene
dc.contributor.authorHope, Sigrun
dc.contributor.authorGardsjord, Erlend Strand
dc.contributor.authorSteen, Nils Eiel
dc.contributor.authorMelle, Ingrid
dc.contributor.authorBrattbakk, Hans-Richard
dc.contributor.authorSteen, Vidar Martin
dc.contributor.authorAukrust, Pål
dc.contributor.authorDjurovic, Srdjan
dc.contributor.authorAndreassen, Ole Andreas
dc.contributor.authorUeland, Thor
dc.date.accessioned2018-11-15T09:55:10Z
dc.date.available2018-11-15T09:55:10Z
dc.date.issued2018-03-23
dc.description.abstractThe Notch signaling pathway plays a crucial role in neurodevelopment and in adult brain homeostasis. We aimed to further investigate Notch pathway activity in bipolar disorder (BD) and schizophrenia (SCZ) by conducting a pathway analysis. We measured plasma levels of Notch ligands (DLL1 and DLK1) using enzyme immunoassays in a large sample of patients (SCZ n = 551, BD n = 246) and healthy controls (HC n = 639). We also determined Notch pathway related gene expression levels by microarray analyses from whole blood in a subsample (SCZ n = 338, BD n = 241 and HC n = 263). We found significantly elevated Notch ligand levels in plasma in both SCZ and BD compared to HC. Significant gene expression findings included increased levels of RFNG and KAT2B (p < 0.001), and decreased levels of PSEN1 and CREBBP in both patient groups (p < 0.001). RBPJ was significantly lower in SCZ vs HC (p < 0.001), and patients using lithium had higher levels of RBPJ (p < 0.001). We provide evidence of altered Notch signaling in both SCZ and BD compared to HC, and suggest that Notch signaling pathway may be disturbed in these disorders. Lithium may ameliorate aberrant Notch signaling. We propose that drugs targeting Notch pathway could be relevant in the treatment of psychotic disorders.en_US
dc.description.sponsorshipKG Jebsen Stiftelsen South East Norway Health Authorityen_US
dc.descriptionSource at <a href=https://doi.org/10.1038/s41598-018-23703-w> https://doi.org/10.1038/s41598-018-23703-w</a>.en_US
dc.identifier.citationHoseth, E.Z., Krull, F., Dieset, I., Mørch, R.H., Hope, S.H., Gardsjord, E.S., ... Ueland, T. (2018). Attenuated Notch signaling in schizophrenia and bipolar disorder. <i>Scientific Reports</i>, 8(5349). https://doi.org/10.1038/s41598-018-23703-wen_US
dc.identifier.cristinIDFRIDAID 1591465
dc.identifier.doi10.1038/s41598-018-23703-w
dc.identifier.issn2045-2322
dc.identifier.urihttps://hdl.handle.net/10037/14183
dc.language.isoengen_US
dc.publisherNature Researchen_US
dc.relation.journalScientific Reports
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/SFF/223273/Norway/Norwegian Centre for Mental Disorders Research/NORMENT/en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/BEHANDLING/248778/Norway/Identifying the missing heritability of complex diseases leveraging biobanks, registries and novel analytical tools in psychiatric disorders//en_US
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Psychiatry, child psychiatry: 757en_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Psykiatri, barnepsykiatri: 757en_US
dc.titleAttenuated Notch signaling in schizophrenia and bipolar disorderen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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