Protein levels of β-catenin and activation state of glycogen synthase kinase-3β in major depression. A study with postmortem prefrontal cortex.
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).


CONCLUSIONS
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.
Geneva University Hospitals, Department of Medical Genetics and Laboratory, 2 ch Petit Bel-Air, CH-1225 Chêne-Bourg, Switzerland; University of Geneva, Department of Psychiatry, University of Geneva, CH-1205 Geneva, Switzerland. Electronic address: felicien.karege@unige.ch.
Félicien
F
Karege
University of Geneva, Department of Psychiatry, University of Geneva, CH-1205 Geneva, Switzerland.
Nader
N
Perroud
Institute of Forensic Medicine (CMU), University of Geneva, CH-1205 Geneva, Switzerland.
Sandra
S
Burkhardt
Geneva University Hospitals, Department of Medical Genetics and Laboratory, 2 ch Petit Bel-Air, CH-1225 Chêne-Bourg, Switzerland.
Rafael
R
Fernandez
Geneva University Hospitals, Department of Medical Genetics and Laboratory, 2 ch Petit Bel-Air, CH-1225 Chêne-Bourg, Switzerland.
Eladia
E
Ballmann
University of Geneva, Department of Psychiatry, University of Geneva, CH-1205 Geneva, Switzerland.
Romano
R
La Harpe
Geneva University Hospitals, Department of Medical Genetics and Laboratory, 2 ch Petit Bel-Air, CH-1225 Chêne-Bourg, Switzerland; University of Geneva, Department of Psychiatry, University of Geneva, CH-1205 Geneva, Switzerland.
Alain
A
Malafosse
D000328:Adult; D000818:Animals; D001344:Autopsy; D003865:Major Depressive Disorder / Q000378:metabolism*; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3