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.
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.
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre Nijmegen, Netherlands.
authors.forename: Shaozheng
authors.initials: S
authors.lastname: Qin
authors.forename: Helena
authors.initials: H
authors.lastname: Cousijn
authors.forename: Mark
authors.initials: M
authors.lastname: Rijpkema
authors.forename: Jing
authors.initials: J
authors.lastname: Luo
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.forename: Erno J
authors.initials: EJ
authors.lastname: Hermans
authors.forename: Guillén
authors.initials: G
authors.lastname: Fernández