TY - JOUR T1 - Catechol-<em>O</em>-Methyltransferase <em>val<sup>158</sup>met</em> Genotype Affects Processing of Emotional Stimuli in the Amygdala and Prefrontal Cortex JF - The Journal of Neuroscience JO - J. Neurosci. SP - 836 LP - 842 DO - 10.1523/JNEUROSCI.1792-04.2005 VL - 25 IS - 4 AU - Michael N. Smolka AU - Gunter Schumann AU - Jana Wrase AU - Sabine M. Grüsser AU - Herta Flor AU - Karl Mann AU - Dieter F. Braus AU - David Goldman AU - Christian Büchel AU - Andreas Heinz Y1 - 2005/01/26 UR - http://www.jneurosci.org/content/25/4/836.abstract N2 - 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. ER -