Félicien Karege1, Nader Perroud2, Sandra Burkhardt3, Rafael Fernandez4, Eladia Ballmann4, Romano La Harpe2, Alain Malafosse5. 1. 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. 2. University of Geneva, Department of Psychiatry, University of Geneva, CH-1205 Geneva, Switzerland. 3. Institute of Forensic Medicine (CMU), University of Geneva, CH-1205 Geneva, Switzerland. 4. Geneva University Hospitals, Department of Medical Genetics and Laboratory, 2 ch Petit Bel-Air, CH-1225 Chêne-Bourg, Switzerland. 5. 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.
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.
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.
Authors: Alejandro Orrico-Sanchez; Laetitia Chausset-Boissarie; Rodolphe Alves de Sousa; Basile Coutens; Sara Rezai Amin; Vincent Vialou; Franck Louis; Assia Hessani; Patrick M Dansette; Teodoro Zornoza; Carole Gruszczynski; Bruno Giros; Bruno P Guiard; Francine Acher; Nicolas Pietrancosta; Sophie Gautron Journal: Mol Psychiatry Date: 2019-10-16 Impact factor: 15.992
Authors: B G Bunney; J Z Li; D M Walsh; R Stein; M P Vawter; P Cartagena; J D Barchas; A F Schatzberg; R M Myers; S J Watson; H Akil; W E Bunney Journal: Mol Psychiatry Date: 2014-11-04 Impact factor: 15.992