Influence of COMT val158met genotype on the depressed brain during emotional processing and working memory

Esther M Opmeer; Rudie Kortekaas; Marie-José van Tol; Nic J A van der Wee; Saskia Woudstra; Mark A van Buchem; Brenda W Penninx; Dick J Veltman; André Aleman

doi:10.1371/journal.pone.0073290

Influence of COMT val158met genotype on the depressed brain during emotional processing and working memory

PLoS One. 2013 Sep 12;8(9):e73290. doi: 10.1371/journal.pone.0073290. eCollection 2013.

Authors

Esther M Opmeer¹, Rudie Kortekaas, Marie-José van Tol, Nic J A van der Wee, Saskia Woudstra, Mark A van Buchem, Brenda W Penninx, Dick J Veltman, André Aleman

Affiliation

¹ Neuroimaging Center, Department of Neuroscience, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Brain / metabolism
Brain / physiology*
Catechol O-Methyltransferase / metabolism
Emotions / physiology*
Female
Genotype
Humans
Magnetic Resonance Imaging
Male
Memory, Short-Term / physiology*
Middle Aged
Prefrontal Cortex / physiology

Substances

Catechol O-Methyltransferase

Grants and funding

The infrastructure for the NESDA study (www.nesda.nl) is funded through the Geestkracht program of the Netherlands Organization for Health Research and Development (Zon-Mw, grant number 10-000-1002) and is supported by participating universities and mental health care organizations (VU University Medical Centre, GGZ inGeest, Arkin, Leiden University Medical Centre, GGZ Rivierduinen, University Medical Centre Groningen, Lentis, GGZ Friesland, GGZ Drenthe, Scientific Institute for Quality of Healthcare (IQ healthcare), Netherlands Institute for Health Services Research (NIVEL) and Netherlands Institute of Mental Health and Addiction (Trimbos Institute). The genotyping of the samples was provided through the Genetic Association Information Network (GAIN). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.