Details

Autor(en) / Beteiligte

• BLASI, Giuseppe
• NAPOLITANO, Francesco
• TODARELLO, Giovanna
• PIVA, Francesco
• PAPAZACHARIAS, Apostolos
• MASELLIS, Rita
• MANCINI, Marina
• PORCELLI, Annamaria
• ROMANO, Raffaella
• RAMPINO, Antonio
• QUARTO, Tiziana
• GIULIETTI, Matteo
• URSINI, Gianluca
• LIPSKA, Barbara K
• KLEINMAN, Joel E
• POPOLIZIO, Teresa
• WEINBERGER, Daniel R
• USIELLO, Alessandro
• BERTOLINO, Alessandro
• DI GIORGIO, Annabella
• CAFORIO, Grazia
• TAURISANO, Paolo
• FAZIO, Leonardo
• GELAO, Barbara
• ATTROTTO, Maria Teresa
• COLAGIORGIO, Lucia

Titel

Association of GSK-3β Genetic Variation With GSK-3β Expression, Prefrontal Cortical Thickness, Prefrontal Physiology, and Schizophrenia

Ist Teil von

• The American journal of psychiatry, 2013-08, Vol.170 (8), p.868-876

Ort / Verlag

Arlington, VA: American Psychiatric Association

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• OBJECTIVE Glycogen synthase kinase 3β (GSK-3β) is an enzyme implicated in neurodevelopmental processes with a broad range of substrates mediating several canonical signaling pathways in the brain. The authors investigated the association of variation in the GSK-3β gene with a series of progressively more complex phenotypes of relevance to schizophrenia, a neurodevelopmental disorder with strong genetic risk. METHOD Based on computer predictions, the authors investigated in humans the association of GSK-3β functional variation with 1) GSK-3β mRNA expression from postmortem prefrontal cortex, 2) GSK-3β and β-catenin protein expression from peripheral blood mononuclear cells (PBMCs), 3) prefrontal imaging phenotypes, and 4) diagnosis of schizophrenia. RESULTS Consistent with predictions, the TT genotype of a single-nucleotide polymorphism in GSK-3β (rs12630592) was associated with reduced GSK-3β mRNA from postmortem prefrontal cortex. Furthermore, this genotype was associated with GSK-3β protein expression and kinase activity, as well as with downstream effects on β-catenin expression in PBMCs. Finally, the TT genotype was associated with attenuated functional MRI prefrontal activity, reduced prefrontal cortical thickness, and diagnosis of schizophrenia. CONCLUSIONS These results suggest that GSK-3β variation is implicated in multiple phenotypes relevant to schizophrenia.