@ARTICLE{10.3389/fnint.2012.00016, AUTHOR={Qin, Shaozheng and Cousijn, Helena and Rijpkema, Mark and Luo, Jing and Franke, Barbara and Hermans, Erno and Fernández, Guillén}, TITLE={The effect of moderate acute psychological stress on working memory-related neural activity is modulated by a genetic variation in catecholaminergic function in humans}, JOURNAL={Frontiers in Integrative Neuroscience}, VOLUME={6}, YEAR={2012}, URL={https://www.frontiersin.org/articles/10.3389/fnint.2012.00016}, DOI={10.3389/fnint.2012.00016}, ISSN={1662-5145}, ABSTRACT={Acute stress has an important impact on higher-order cognitive functions supported by the prefrontal cortex (PFC) such as working memory (WM). In rodents, such effects are mediated by stress-induced alterations in catecholaminergic signaling, but human data in support of this notion is lacking. A common variation in the gene encoding Catechol-O-methyltransferase (COMT) is known to affect basal catecholaminergic availability and PFC functions. Here, we investigated whether this genetic variation (Val158Met) modulates effects of stress on WM-related neural activity in humans. In a counterbalanced crossover design, 41 healthy young men underwent functional magnetic resonance imaging (fMRI) while performing a numerical N-back WM task embedded in a stressful or neutral context. Moderate psychological stress was induced by a well-controlled procedure involving viewing strongly aversive (versus emotionally neutral) movie material in combination with a self-referencing instruction. Acute stress resulted in genotype-dependent effects on WM performance and WM-related activation in the dorsolateral PFC, with a relatively negative impact of stress in COMT Met-homozygotes as opposed to a relatively positive effect in Val-carriers. A parallel interaction was found for WM-related deactivation in the anterior medial temporal lobe (MTL). Our findings suggest that individuals with higher baseline catecholaminergic availability (COMT Met-homozygotes) appear to reach a supraoptimal state under moderate levels of stress. In contrast, individuals with lower baselines (Val-carriers) may reach an optimal state. Thus, our data show that effects of acute stress on higher-order cognitive functions vary depending on catecholaminergic availability at baseline, and thereby corroborate animal models of catecholaminergic signaling that propose a non-linear relationship between catecholaminergic activity and prefrontal functions.} }