Platelet MAO activity and COMT Val158Met genotype interaction predicts visual working memory updating efficiency

The exact mechanism how serotonergic and dopaminergic systems relate to one another in working memory (WM) updating is unknown. Platelet monoamine oxidase (MAO) has been used as a marker for central serotonergic capacity, and catechol-O-methyltransferase (COMT) as a marker for central dopaminergic capacity. This study aimed to describe the interaction of platelet MAO activity and COMT Val158Met genotype in visual working memory updating: the ability to replace old information with new within hundreds of milliseconds. Previous studies suggest that platelet MAO activity and COMT Val158Met genotype could have an interaction effect on working memory. However, there are no studies that have directly examined the interaction of these biomarkers in WM updating. We used a 2-back updating task with facial expressions and defined updating efficiency as response times for correct responses. 455 subjects from a population representative sample were included. Mixed models were used for data analysis with an aim to study the interaction of COMT Val158Met genotype (Val/Val, Val/Met and Met/Met) and the level of MAO activity (high vs low). Education, IQ, sex, simple reaction times, and overall updating accuracy were included as covariates. We found that the effect of COMT Val158Met on updating efficiency depends on the level of platelet MAO activity. Low MAO in contrast to high MAO was associated with an increase in updating efficiency in Val/Met but a decrease in Met/Met. The results are discussed in the context of serotonin and dopamine functions in brain regions related to WM. The findings support the view that serotonin modulates dopaminergic activation in updating and contribute to understanding the role of serotonin in PFC, top-down inhibitory signals, and its interactions with dopamine in WM processes.