This Article  • Full text  • PDF  • eFigures and eTable  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Contact me when this article is cited  Related Content  • Related article  • Similar articles in this journal  Topic Collections  • Neurology  • Depression  • Genetics  • Genetic Disorders  • Alert me on articles by topic  Social Bookmarking   What's this?

Becky Inkster, DPhil; Thomas E. Nichols, PhD; Philipp G. Saemann, MD; Dorothee P. Auer, MD; Florian Holsboer, MD, PhD; Pierandrea Muglia, MD; Paul M. Matthews, DPhil, FRCP

Arch Gen Psychiatry. 2009;66(7):721-728.

Context  Indirect evidence suggests that the glycogen synthase kinase-3β (GSK3β) gene might be implicated in major depressive disorder (MDD).

Background  We evaluated 15 GSK3β single-nucleotide polymorphisms (SNPs) to test for associations with regional gray matter (GM) volume differences in patients with recurrent MDD. We then used the defined regions of interest based on significant associations to test for MDD x genotype interactions by including a matched control group without any psychiatric disorder, including MDD.

Design  General linear model with nonstationary cluster-based inference.

Setting  Munich, Germany.

Participants  Patients with recurrent MDD (n = 134) and age-, sex-, and ethnicity-matched healthy controls (n = 143).

Main Outcome Measures  Associations between GSK3β polymorphisms and regional GM volume differences.

Results  Variation in GM volume was associated with GSK3β 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).

Conclusions  The GSK3β 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 GSK3β 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 GSK3β 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.

Author Affiliations: GlaxoSmithKline Clinical Imaging Centre, Hammersmith Hospital, London, England (Drs Inkster, Nichols, and Matthews); Max Planck Institute of Psychiatry, Munich, Germany (Drs Saemann, Auer, and Holsboer); Genetics Division, Drug Discovery, Medicine Development Centre, GlaxoSmithKline, Research and Development, Verona, Italy (Dr Muglia); Department of Clinical Neurosciences, Imperial College, London (Dr Matthews).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED ARTICLE

This Month in Archives of General Psychiatry
Arch Gen Psychiatry. 2009;66(7):690.
FULL TEXT