Citation

Karege F, Perroud N, Burkhardt S, Fernandez R, Ballmann E, La Harpe R, Malafosse A. J. Affect. Disord. 2012; 136(1-2): 185-188.

Copyright

(Copyright © 2012, Elsevier Publishing)

DOI

10.1016/j.jad.2011.09.024

PMID

22036797

Abstract

BACKGROUND: The Wnt/GSK3β signaling pathway was implicated in mood disorders. Beta-catenin is a protein targeted by this signaling axis. We aimed to examine whether there is an abnormality in this signaling axis in major depression.
METHODS: Postmortem brains from 20 depressed and 20 non-depressed subjects were used. In both groups, suicide and non-suicide were included in equal number. Protein levels of β-catenin, tGSK3β and ser(9)-pGSK3β were determined in prefrontal cortex.
RESULTS: ANOVA yielded significant variations between groups in β-catenin (F(3,36)=19.5; p<0.001) and pGSK3β protein (F(3,36)=14.3; p<0.001) and in tGSK3β-to-pGSK3β ratio (F(3,36)=10.9; p<0.001). Fisher tests showed decrease in both groups of MDD and MDD with suicide (MDD+S) for β-catenin (p<0.001) and pGSK3β levels (p<0.001) respectively. The tGSK3β-to-pGSK3β ratio was increased in MDD and MDD+S subjects (p<0.001). A negative correlation was observed between β-catenin levels and the activation state of the GSK3β (r2=0.358; p<0.005).
LIMITATIONS: The sample was small and only a fraction of s(9)-pGSK3β, albeit significant, was used and; the mood state at the time of death was unknown.
CONCLUSIONS: The study observed a dysregulation of Wnt/GSK3β signaling associated with a lifetime of major depression. The study may have relevance in further development of drugs based on GSK3β inhibition.

Language: en

Keywords

Humans; Adult; Female; Male; Middle Aged; Autopsy; Animals; Rats; Depressive Disorder, Major; Prefrontal Cortex; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; beta Catenin; Wnt Signaling Pathway