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. 2005 Jan 26;25(4):836-42.
doi: 10.1523/JNEUROSCI.1792-04.2005.

Catechol-O-methyltransferase val158met genotype affects processing of emotional stimuli in the amygdala and prefrontal cortex

Michael N Smolka  1 , Gunter Schumann, Jana Wrase, Sabine M Grüsser, Herta Flor, Karl Mann, Dieter F Braus, David Goldman, Christian Büchel, Andreas Heinz
Affiliations

Catechol-O-methyltransferase val158met genotype affects processing of emotional stimuli in the amygdala and prefrontal cortex

Michael N Smolka et al. J Neurosci. .

Abstract

Catechol-O-methyltransferase (COMT) degrades the catecholamine neurotransmitters dopamine, epinephrine, and norepinephrine. A functional polymorphism in the COMT gene (val158met) accounts for a fourfold variation in enzyme activity. The low-activity met158 allele has been associated with improved working memory but with higher risk for anxiety-related behaviors. Using functional magnetic resonance imaging, we assessed the effects of COMT genotype on brain activation by standardized affective visual stimuli (unpleasant, pleasant, and neutral) in 35 healthy subjects. The analysis of genotype effects was restricted to brain areas with robust activation by the task. To determine genedose effects, the number of met158 alleles (0, 1, or 2) was correlated with the blood oxygen level-dependent (BOLD) response elicited by pleasant or unpleasant stimuli compared with neutral stimuli. COMT genotype had no significant impact on brain activation by pleasant stimuli but was related to the neural response to unpleasant stimuli: reactivity to unpleasant stimuli was significantly positively correlated with the number of met158 alleles in the limbic system (left hippocampus, right amygdala, right thalamus), connected prefrontal areas (bilateral ventrolateral prefrontal cortex, right dorsolateral prefrontal cortex), and the visuospatial attention system (bilateral fusiform gyrus, left inferior parietal lobule). Genotype explained up to 38% of interindividual variance in BOLD response elicited by unpleasant stimuli. We conclude that (1) genetic variations can account for a substantial part of interindividual variance in task-related brain activation and that (2) increased limbic and prefrontal activation elicited by unpleasant stimuli in subjects with more met158 alleles might contribute to the observed lower emotional resilience against negative mood states.

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Figures

Figure 1.
Figure 1.
Brain areas activated by pleasant and unpleasant emotional stimuli compared with neutral stimuli (p < 0.01; uncorrected; cluster size ≥10 voxels) and used as VOI in the task × genotype analyses.
Figure 2.
Figure 2.
Correlation between COMT met158 allele dosage (0 = val/val, 1 = val/met, or 2 = met/met) and activation by unpleasant stimuli of the ventrolateral PFC (A), right amygdala (B), and left dorsal hippocampus (C). Left, Statistical maps are shown (p < 0.05 corrected for volume of mask; cluster size ≥10 voxels). Right, Neural responses of individuals are displayed related to COMT genotype. Individual BOLD responses were extracted from the voxel with the highest t value inside the cluster encircled at the left.
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