Exploring the Wnt signaling pathway in schizophrenia and bipolar disorder

被引：109

作者：

Hoseth, Eva Z. ^{[1
,2
,3
]}

Krull, Florian ^{[1
,2
]}

Dieset, Ingrid ^{[1
,2
]}

Morch, Ragni H. ^{[1
,2
]}

Hope, Sigrun ^{[1
,2
,4
]}

Gardsjord, Erlend S. ^{[1
,2
]}

Steen, Nils Eiel ^{[1
,2
]}

Melle, Ingrid ^{[1
,2
]}

Brattbakk, Hans-Richard ^{[5
,6
]}

Steen, Vidar M. ^{[5
,6
]}

Aukrust, Pal ^{[7
,8
,9
,10
]}

Djurovic, Srdjan ^{[11
,12
]}

Andreassen, Ole A. ^{[1
,2
]}

Ueland, Thor ^{[7
,9
,10
,13
]}

机构：

[1] Univ Oslo, KG Jebsen Ctr Psychosis Res, Inst Clin Med, NORMENT, Oslo, Norway

[2] Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway

[3] More & Romsdal Hosp Trust, Div Mental Hlth & Addict, Kristiansand, Norway

[4] Oslo Univ Hosp, Div Neurol, Dept Neurohabil, Oslo, Norway

[5] Univ Bergen, KG Jebsen Ctr Psychosis Res, Dept Clin Sci, NORMENT KG, Oslo, Norway

[6] Haukeland Hosp, Ctr Med Genet & Mol Med, Dr Einar Martens Res Grp Biol Psychiat, Oslo, Norway

[7] Natl Hosp Norway, Oslo Univ Hosp, Res Inst Internal Med, Oslo, Norway

[8] Natl Hosp Norway, Oslo Univ Hosp, Sect Clin Immunol & Infect Dis, Oslo, Norway

[9] Natl Hosp Norway, Oslo Univ Hosp, Inst Clin Med, Oslo, Norway

[10] Univ Oslo, KG Jensen Inflammatory Res Ctr, Oslo, Norway

[11] Oslo Univ Hosp, Dept Med Genet, Oslo, Norway

[12] Univ Bergen, Dept Clin Sci, NORMENT, KG Jebsen Ctr Psychosis Res, Bergen, Norway

[13] Univ Tromso, KG Jebsen Thrombosis Res & Expertise Ctr, Tromso, Norway

来源：

TRANSLATIONAL PSYCHIATRY | 2018年 / 8卷

关键词：

GENOME-WIDE ASSOCIATION; PREFRONTAL CORTEX; NUCLEAR FACTOR; BETA-CATENIN; SERUM-LEVELS; FZD3; GENE; CELLS; PROTEIN; ABNORMALITIES; SCLEROSTIN;

D O I：

10.1038/s41398-018-0102-1

中图分类号：

R749 [精神病学];

学科分类号：

100205 ;

摘要：

The 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 x 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.

引用

页数：10

共 80 条

[1] Wnt5a is elevated in heart failure and affects cardiac fibroblast function [J].