Open AccessInfluence of COMT val158met Genotype on the Depressed Brain during Emotional Processing and Working Memory
Author(s) -
Esther M. Opmeer,
Rudie Kortekaas,
Marie-José van Tol,
Nic J.A. van der Wee,
Saskia Woudstra,
Mark A. van Buchem,
Brenda W. J. H. Penninx,
Dick J. Veltman,
André Alemán
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0073290
Subject(s) - endophenotype , functional magnetic resonance imaging , working memory , psychology , prefrontal cortex , catechol o methyl transferase , major depressive disorder , amygdala , neuroscience , parahippocampal gyrus , neuroimaging , genotype , cognition , temporal lobe , biology , genetics , epilepsy , gene
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.