Catechol-O-methyltransferase val 158 met genotype determines effect of reboxetine on emotional memory in healthy male volunteers

The catechol-O-methyltransferase (COMT) enzyme is responsible for degradation of catecholamines, such as dopamine (DA) and noradrenaline. The substitution of methionine (met) for valine (val) at codon 158 in the COMT gene is associated with a 40% reduction in enzyme activity and higher levels of extracelluar DA. This single nucleotide polymorphism has been most extensively studied in relation to cognitive function; several studies have linked the lowactivity met allele to enhanced performance on prefrontal cortex (PFC) tasks compared with the high-activity val allele, albeit with some inconsistencies. In addition, there is evidence suggesting COMT involvement in emotional processing. Several studies have demonstrated increased limbic–prefrontal activation in response to negative emotional stimuli in healthy met carriers. This has been taken to represent less efficient emotional processing in met, compared with val, allele carriers. Other studies have found the reverse pattern — increased limbic reactivity in response to emotional stimuli in val, compared with met carriers. However, a meta-analysis of functional neuroimaging