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dc.contributor.authorHoseth, Eva Zsuzsannaen_US
dc.contributor.authorKrull, Florianen_US
dc.contributor.authorDieset, Ingriden_US
dc.contributor.authorMørch, Ragni Heleneen_US
dc.contributor.authorHope, Sigrunen_US
dc.contributor.authorGardsjord, Erlend Stranden_US
dc.contributor.authorSteen, Nils Eielen_US
dc.contributor.authorMelle, Ingriden_US
dc.contributor.authorBrattbakk, Hans-Richarden_US
dc.contributor.authorSteen, Vidar Martinen_US
dc.contributor.authorAukrust, Pålen_US
dc.contributor.authorDjurovic, Srdjanen_US
dc.contributor.authorAndreassen, Ole Andreasen_US
dc.contributor.authorUeland, Thoren_US
dc.PublishedHoseth Ez, Krull F, Dieset I, Mørch RH, Hope SH, Gardsjord ES, Steen NE, Melle I, Brattbakk H, Steen VM, Aukrust P, Djurovic S, Andreassen OA, Ueland T. Exploring the Wnt signaling pathway in schizophrenia and bipolar disorder. Translational psychiatry. 2018;8:55eng
dc.description.abstractThe Wnt signaling pathway plays a crucial role in neurodevelopment and in regulating the function and structure of the adult nervous system. Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental disorders with evidence of subtle neurodevelopmental, structural and functional neuronal abnormalities. We aimed to elucidate the role of aberrant regulation of the Wnt system in these disorders by evaluating plasma levels of secreted Wnt modulators in patients (SCZ = 551 and BD = 246) and healthy controls (HCs = 639) using enzyme immune-assay. We also investigated the expression of 141 Wnt-related genes in whole blood in a subsample (SCZ = 338, BD = 241, and HCs = 263) using microarray analysis. Both SCZ and BD had dysregulated mRNA expression of Wnt-related genes favoring attenuated canonical (beta-catenin-dependent) signaling, and there were also indices of enhanced non-canonical Wnt signaling. In particular, FZD7, which may activate all Wnt pathways, but favors non-canonical signaling, and NFATc3, a downstream transcription factor and readout of the non-canonical Wnt/Ca2+ pathway, were significantly increased in SCZ and BD (p < 3 × 10−4). Furthermore, patients had lower plasma levels of soluble dickkopf 1 and sclerostin (p < 0.01) compared with HC. Our findings suggest that SCZ and BD are characterized by abnormal Wnt gene expression and plasma protein levels, and we propose that drugs targeting the Wnt pathway may have a role in the treatment of severe mental disorders.en_US
dc.publisherSpringer Natureeng
dc.rightsAttribution CC BYeng
dc.titleExploring the Wnt signaling pathway in schizophrenia and bipolar disorderen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2018 The Author(s)
dc.source.journalTranslational psychiatry
dc.relation.projectNorges forskningsråd: 248778
dc.relation.projectHelse Sør-Øst RHF: 2017-112
dc.relation.projectStiftelsen Kristian Gerhard Jebsen: SKGJ-MED-008
dc.relation.projectNorges forskningsråd: 223273

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