Academic journal article Cognitive, Affective and Behavioral Neuroscience

Catechol-O-Methyltransferase Val^sup 158^met Genotype Affects Neural Correlates of Aversive Stimuli Processing

Academic journal article Cognitive, Affective and Behavioral Neuroscience

Catechol-O-Methyltransferase Val^sup 158^met Genotype Affects Neural Correlates of Aversive Stimuli Processing

Article excerpt

It was previously shown that variation of the catechol-O-methyltransferase (COMT) gene modulates brain activity during the processing of stimuli with negative valence, but not for pleasant stimuli. Here, we tested whether the COMT genotype also modulates the electrophysiological correlates of emotional processing and explored whether the environmental factor of life stress influences this effect. Using the early posterior negativity (EPN) paradigm, event-related brain potentials were measured in 81 healthy individuals during the processing of pictures that evoked emotions of positive and negative valence. As was hypothesized, the COMT genotype affected the EPN amplitudes for unpleasant stimuli, but not for pleasant ones. Specifically, Met/Met carriers respond more sensitively to unpleasant stimuli, as compared with Val/Val carriers. We did not find evidence that life stress moderates the effect of the COMT genotype on emotional stimuli processing.

Catechol-O-methyltransferase (COMT), which degrades the catecholamine neurotransmitters dopamine, epinephrine, and norepinephrine, has recently gained increasing interest with respect to emotional and cognitive brain functions. A common single nucleotide polymorphism exists in the COMT gene, causing a Val-to-Met substitution at amino acid position 158, which is commonly designated as Val158Met. The Met variant corresponds to the so-called thermo-labile enzyme, displaying lower enzymatic activity. This results in increased synaptic dopamine and strengthened (prefrontal) dopaminergic tone. Met/Met homozygotes exhibit approximately 25% COMT activity of Val/Val homozygotes, with heterozygotes in between (Lotta et al., 1995). The Val variant is associated with an impaired cognitive performance (the first positive results of impaired cognitive performance were not confirmed by a recent meta-analysis [Barnett, Scoriels, & Munafò, 2008]) but seems to provide increased emotional resilience against negative mood states and various psychiatric disorders (Heinz & Smolka, 2006).

Investigation of the effects of COMT Val158Met variation on functional brain activity during emotional stimuli processing, using functional magnetic resonance imaging (fMRI), revealed a positive association between the gene dose coding for Met variants and the functional brain activity in the amygdala for unpleasant stimuli, but not for pleasant ones (Smolka et al., 2007; Smolka et al., 2005). Consistent with these fMRI results, a recent study showed that the COMT genotype significantly affected startle reflex modulation by aversive stimuli, which can be considered a psychophysiological measure of emotion processing (Montag et al., 2008). In this study, subjects homozygous for the Met allele exhibited a potentiated startle reflex, as compared with Val allele carriers. Similar effects of the COMT genotype were found for the activity of the ventral striatum during reward processing. In this area of the brain, stronger responses to loss incentives were described with an increasing number of Met alleles (Schmack et al., 2008), without any significant effect of the COMT genotype on ventral striatum activation during reward incentives (Forbes et al., 2009; Schmack et al., 2008). Since COMT has been found to be expressed not only within the prefrontal cortex, but also in the human amygdala and striatum (Hong, Shu-Leong, Tao, & Lap-Ping, 1998), it might well be that elevated dopamine in Met158 homozygotes in the ventral striatum and amygdala enhances the salience of environmental threat cues. This would be in line with a recent positron emission tomography study (Kienast et al., 2008) showing that dopamine storage capacity in the human amygdala was positively correlated with fMRI blood-oxygen-level-dependent signal changes in the amygdala that were evoked by aversive stimuli.

Alternatively, the model of tonic and phasic dopamine signaling (Bilder, Volavka, Lachman, & Grace, 2004) suggests that elevated dopamine in the prefrontal cortex could result in an inflexible attentional focus on aversive stimuli. …

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