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PW01-19 - Rumination is Influenced by a Genetic Interaction Between GIRK2 Receptor and CREB in Two Independent European Samples

Published online by Cambridge University Press:  17 April 2020

J. Lazary ,
G. Juhasz ,
I. Anderson ,
J.F. Deakin  and
G. Bagdy
J. Lazary
Affiliation:
Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary
G. Juhasz
Affiliation:
Neuroscience and Psychiatry Unit, The University of Manchester, Manchester, UK
I. Anderson
Affiliation:
Neuroscience and Psychiatry Unit, The University of Manchester, Manchester, UK
J.F. Deakin
Affiliation:
Neuroscience and Psychiatry Unit, The University of Manchester, Manchester, UK
G. Bagdy
Affiliation:
Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary

Abstract

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Objectives

Rumination is a significant cognitive symptom of depression. As rumination is strongly related to altered memory function we selected two genes previously described as important candidates for both depression and memory processing to assess their contribution to rumination. Based on a possible functional role for cAMP-dependent protein kinase in the mechanism of action antidepressants, we studied the association between G protein-activated K+ channel 2 (GIRK2) and cAMP-response element binding (CREB) protein genes and rumination in two independent European samples.

Methods

We genotyped an exonic SNP (rs2070995) in GIRK2 gene and a promoter SNP (rs2253206) in CREB gene of 611 individuals from Budapest and 1174 individuals from Manchester. Rumination was measured by Ruminative Response Scale (RRS) of Response Style Questionnaire. Generalized linear models (GLMs) were performed for single marker associations. Likelihood ratio tests were used for interactions between genetic markers on RRS.

Results

Single marker associations did not provide any significant individual effect of the two SNPs on rumination. However, interaction analyses revealed a strongly significant interaction between the rs2070995 and rs2253206 on RRS in both European samples (pBudapest=0.00099; pManchester=0.0027). Homozygous TT individuals for rs2070995 in interaction with homozygous GG for rs2253206 scored significantly higher on RRS compared with other genotypes.

Conclusion

Our results suggest that two key post-receptor signalling proteins, GIRK2 and CREB, interact with each other in regulating the process of rumination which may have relevance for depression and its treatment.

These studies were supported by the Sixth Framework Programme of the EU, LSHM-CT-2004-503474, HRF T03298/2000.

Type
Affective disorders / Unipolar depression / Bipolar disorder
Information
European Psychiatry , Volume 25 , Issue S1: 18th European Congress of Psychiatry. February 27, March 2, 2010 - Munich, Germany , 2010 , 25-E1421
Copyright
Copyright © European Psychiatric Association 2010
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