Influence of COMT val158met Genotype on the Depressed Brain during Emotional Processing and Working Memory

Esther M. Opmeer*, Rudie Kortekaas, Marie-Jose van Tol, Nic J. A. van der Wee, Saskia Woudstra, Mark A. van Buchem, Brenda W. Penninx, Dick J. Veltman, Andre Aleman

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Major depressive disorder (MDD) has been associated with abnormal prefrontal-limbic interactions and altered catecholaminergic neurotransmission. The val158met polymorphism on the catechol-O-methyltransferase (COMT) gene has been shown to influence prefrontal cortex (PFC) activation during both emotional processing and working memory (WM). Although COMT-genotype is not directly associated with MDD, it may affect MDD pathology by altering PFC activation, an endophenotype associated with both COMT and MDD. 125 participants, including healthy controls (HC, n=28) and MDD patients were genotyped for the COMT val158met polymorphism and underwent functional magnetic resonance imaging (fMRI-neuroimaging) during emotion processing (viewing of emotional facial expressions) and a WM task (visuospatial planning). Within HC, we observed a positive correlation between the number of met-alleles and right inferior frontal gyrus activation during emotional processing, whereas within patients the number of met-alleles was not correlated with PFC activation. During WM a negative correlation between the number of met-alleles and middle frontal gyrus activation was present in the total sample. In addition, during emotional processing there was an effect of genotype in a cluster including the amygdala and hippocampus. These results demonstrate that COMT genotype is associated with relevant endophenotypes for MDD. In addition, presence of MDD only interacts with genotype during emotional processing and not working memory.

Original languageEnglish
Article numbere73290
Number of pages9
JournalPLoS ONE
Volume8
Issue number9
DOIs
Publication statusPublished - 12-Sep-2013

Keywords

  • CATECHOL-O-METHYLTRANSFERASE
  • DOPAMINE REGULATING GENES
  • VAL(158)MET GENOTYPE
  • PSYCHOMETRIC PROPERTIES
  • PREFRONTAL DYSFUNCTION
  • MAJOR DEPRESSION
  • AVERSIVE STIMULI
  • LONDON TASK
  • DISORDER
  • AMYGDALA

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