Association of GSK-3β genetic variation with GSK-3β expression, prefrontal cortical thickness, prefrontal physiology, and schizophrenia

Giuseppe Blasi, Francesco Napolitano, Gianluca Ursini, Annabella Di Giorgio, Grazia Caforio, Paolo Taurisano, Leonardo Fazio, Barbara Gelao, Maria Teresa Attrotto, Lucia Colagiorgio, Giovanna Todarello, Francesco Piva, Apostolos Papazacharias, Rita Masellis, Marina Mancini, Annamaria Porcelli, Raffaella Romano, Antonio Rampino, Tiziana Quarto, Matteo GiuliettiBarbara K. Lipska, Joel E. Kleinman, Teresa Popolizio, Daniel R. Weinberger, Alessandro Usiello, Alessandro Bertolino

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)868-876
Number of pages9
JournalAmerican Journal of Psychiatry
Issue number8
StatePublished - Aug 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Psychiatry and Mental health


Dive into the research topics of 'Association of GSK-3β genetic variation with GSK-3β expression, prefrontal cortical thickness, prefrontal physiology, and schizophrenia'. Together they form a unique fingerprint.

Cite this