Epistatic interaction of CREB1 and KCNJ6 on rumination and negative emotionality

J. Lazáry, G. Juhász, Ian M. Anderson, Christian P. Jacob, T. Trang Nguyen, Klaus Peter Lesch, Andreas Reif, J. F William Deakin, G. Bagdy

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

G protein-activated K+ channel 2 (GIRK2) and cAMP-response element binding protein (CREB1) are involved in synaptic plasticity and their genes have been implicated depression and memory processing. Excessive rumination is a core cognitive feature of depression which is also present in remission. High scores on the Ruminative Response Scale (RRS) questionnaire are predictive of relapse and recurrence. Since rumination involves memory, we tested the hypothesis that variation in the genes encoding GIRK2 (KCNJ6) and CREB1 mechanisms would influence RRS scores. GIRK2 and CREB1 polymorphisms were studied in two independent samples (n = 651 and n = 1174) from the general population. Strongly significant interaction between the TT genotype of rs2070995 (located in KCNJ6) and the GG genotype of rs2253206 (located in CREB1) on RRS were found in both samples. These results were validated in an independent third sample (n = 565; individuals with personality disorders) showing significant main effect of the variants mentioned as well as significant interaction on a categorical diagnosis of Cluster C personality disorder (obsessional-compulsive, avoidant and dependent) in which rumination is a prominent feature. Our results suggest that genetic epistasis in post-receptor signaling pathways in memory systems may have relevance for depression and its treatment.

Original languageEnglish
Pages (from-to)63-70
Number of pages8
JournalEuropean Neuropsychopharmacology
Volume21
Issue number1
DOIs
Publication statusPublished - Jan 2011

Fingerprint

Depression
Dependent Personality Disorder
Genetic Epistasis
Compulsive Personality Disorder
Genotype
Recurrence
Cyclic AMP Response Element-Binding Protein
Neuronal Plasticity
Personality Disorders
GTP-Binding Proteins
Genes
Population
Surveys and Questionnaires
protein K

Keywords

  • Depression
  • Genetic interaction;
  • GIRK2;
  • Personality disorder;
  • Rumination;

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Pharmacology (medical)
  • Biological Psychiatry
  • Neurology
  • Pharmacology

Cite this

Epistatic interaction of CREB1 and KCNJ6 on rumination and negative emotionality. / Lazáry, J.; Juhász, G.; Anderson, Ian M.; Jacob, Christian P.; Nguyen, T. Trang; Lesch, Klaus Peter; Reif, Andreas; Deakin, J. F William; Bagdy, G.

In: European Neuropsychopharmacology, Vol. 21, No. 1, 01.2011, p. 63-70.

Research output: Contribution to journalArticle

Lazáry, J. ; Juhász, G. ; Anderson, Ian M. ; Jacob, Christian P. ; Nguyen, T. Trang ; Lesch, Klaus Peter ; Reif, Andreas ; Deakin, J. F William ; Bagdy, G. / Epistatic interaction of CREB1 and KCNJ6 on rumination and negative emotionality. In: European Neuropsychopharmacology. 2011 ; Vol. 21, No. 1. pp. 63-70.
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