Polymorphisms within the metabotropic glutamate receptor 1 gene are associated with depression phenotypes

Menke, Andreas and Sämann, Philipp and Kloiber, Stefan and Czamara, Darina and Lucae, Susanne and Hennings, Johannes and Heck, Angela and Kohli, Martin A. and Czisch, Michael and Müller-Myhsok, Bertram and Holsboer, Florian and Binder, Elisabeth B.. (2011) Polymorphisms within the metabotropic glutamate receptor 1 gene are associated with depression phenotypes. Psychoneuroendocrinology, 37 (4). pp. 565-575.

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Official URL: http://edoc.unibas.ch/46941/

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OBJECTIVES: Glutamate has been implicated in the pathophysiology and treatment of mood disorders possibly by affecting the regulation of the hypothalamus-pituitary-adrenocortical (HPA) axis. Growing evidence suggests an important role of the metabotropic glutamate receptor 1 (mGlu1) in depression-related phenotypes. To test whether these findings can also be supported by human genetics data, we explored polymorphisms within the metabotropic glutamate receptor 1 gene (GRM1) for their association with unipolar depression (UPD) as well as with biological phenotypes of this disorder. METHODS: We first tested the association of 43 tag-SNPs covering the GRM1 locus with UPD in 350 patients and 370 matched controls. We then investigated the effects of the associated SNPs on hippocampal glutamate levels estimated using (1)H-MR-spectroscopy ((1)H-MRS) and on endocrine measures from the combined dexamethasone-suppression/CRH stimulation (dex/CRH) test. RESULTS: Within the GRM1 locus, 22 SNPs showed nominally significant association with UPD, of which 6 withstood corrections for multiple testing (rs2268666 with best allelic p=7.0×10(-5)). Supportive evidence for an association with UPD was gained from a second independent sample with 904 patients and 1012 controls. Furthermore, patients homozygous for the non-risk genotypes showed reduced hippocampal glutamate levels as measured by (1)H-MRS, a more pronounced normalization of HPA-axis hyperactivity as well as a better antidepressant treatment outcome. CONCLUSIONS: These results suggest that the combination of genetic and biological markers may allow to subgroup patients into etiopathogenetically more relevant subcategories which could guide clinicians in their antidepressant treatment choices.
Faculties and Departments:07 Faculty of Psychology > Departement Psychologie
UniBasel Contributors:Heck, Angela
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:30 Nov 2017 07:55
Deposited On:30 Nov 2017 07:55

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