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Interval Timing Shows Selective Enhancement Under Psychosocial Stress: A Cortisol-Mediated Dissociation From Spatial Processing

Gumus-Akay, G.; Vatansever, G.; Cetinkaya, F.; Varol, N.; Cicek, M.

2025-11-10 neuroscience
10.1101/2025.11.07.686532 bioRxiv
Show abstract

Acute stress affects cognitive processes, including our perception of time, yet few studies have examined how HPA axis activation specifically modulates time perception. This study provides the first systematic examination of how psychosocial stress influences temporal versus spatial reproduction using the Trier Social Stress Test (TSST), investigating underlying epigenetic mechanisms. Forty-four healthy adults (21 men; mean age 21.96 {+/-} 3.03) completed temporal and spatial reproduction tasks before and after TSST, with salivary cortisol sampling and DNA methylation analysis of four dopamine-related genes (COMT, DRD2, SLC6A3, TH). The TSST successfully elevated cortisol and state anxiety, confirming effective HPA axis activation. Critically, stress selectively reduced temporal underestimation. Despite their shared neurocognitive mechanisms, spatial processing remained unchanged. This demonstrates that HPA-mediated stress enhances interval timing. Men demonstrated greater stress-induced improvement in temporal accuracy than women, while neither sex showed significant spatial changes, independent of cortisol reactivity differences. The results are discussed in the context of dopaminergic models of temporal processing. Exploratory epigenetic analyses revealed a DRD2 methylation x cortisol response interaction for temporal tasks, with higher methylation associated with greater stress-induced improvement among high cortisol responders. However, sensitivity analysis indicated these interactions were driven by participants with extreme methylation values, limiting generalizability of epigenetic results. These findings demonstrate that acute psychosocial stress selectively enhances temporal accuracy, potentially through cortisol-dopamine interactions in corticostriatal timing circuits. This work opens avenues for investigating stress-timing mechanisms and cortisol-dopamine interactions in timing circuits, and provides preliminary evidence for epigenetic moderation.

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