Study Report

CitationInkster, 2009 PubMed
Full InfoInkster, B., Nichols, T.E., Saemann, P.G., Auer, D.P., Holsboer, F., Muglia, P. and Matthews, P.M. (2009) Association of GSK3beta polymorphisms with brain structural changes in major depressive disorder. Arch Gen Psychiatry, 66, 721-728.

Hypothesis or Background Indirect evidence suggests that the glycogen synthase kinase-3beta (GSK3beta) gene might be implicated in major depressive disorder (MDD).
Sample InformationPatients with recurrent MDD (n = 134) and age-, sex-, and ethnicity-matched healthy controls (n = 143)
Method Detail
Method Keywordsgenotyping; magnetic resonance imaging (MRI)
ResultVariation in GM volume was associated with GSK3beta polymorphisms; the most significant associations were found for rs6438552, a putative functional intronic SNP that showed 3 significant GM clusters in the right and left superior temporal gyri and the right hippocampus (P < .001, P = .02, and P = .02, respectively, corrected for multiple comparisons across the whole brain). Similar results were obtained with rs12630592, an SNP in high linkage disequilibrium. A significant SNP x MDD status interaction was observed for the effect on GM volumes in the right hippocampus and superior temporal gyri (P < .001 and P = .01, corrected, respectively).
ConclusionsThe GSK3beta gene may have a role in determining regional GM volume differences of the right hippocampus and bilateral superior temporal gyri. The association between genotype and brain structure was specific to the patients with MDD, suggesting that GSK3beta genotypes might interact with MDD status. We speculate that this is a consequence of regional neocortical, glial, or neuronal growth or survival. In considering core cognitive features of MDD, the association of GSK3beta polymorphisms with structural variation in the temporal lobe and hippocampus is of particular interest in the context of other evidence for structural and functional abnormalities in the hippocampi of patients with MDD.

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