The association of the 5-HTTLPR polymorphism and the response to different stressors in healthy males

Leandra Kuhn,Ute Habel,Birgit Derntl,Vanessa Nieratschker,Christina Schulte,Hannes Noack,Ann-Kristin Röhr,Lisa Wagels,Sana Eisenkolb,Nadine Skoluda

doi:10.1007/s00702-021-02390-4

Abstract

The experience of stress is related to individual wellbeing and vulnerability to psychopathology. Therefore, understanding the determinants of individual differences in stress reactivity is of great concern from a clinical perspective. The functional promotor polymorphism of the serotonin transporter gene (5-HTTLPR/rs25531) is such a factor, which has been linked to the acute stress response as well as the adverse effect of life stressors. In the present study, we compared the impact of two different stress induction protocols (Maastricht Acute Stress Test and ScanSTRESS) and the respective control conditions on affective ratings, salivary cortisol levels and cognitive performance. To this end, 156 healthy young males were tested and genotyped for the 5-HTTLPR/rs25531 polymorphism. While combined physiological and psychological stress in the MAST led to a greater cortisol increase compared to control conditions as well as the psychosocial ScanSTRESS, subjective stress ratings were highest in the ScanSTRESS condition. Stress induction in general affected working memory capacity but not response inhibition. Subjective stress was also influenced by 5-HTTLPR/rs25531 genotype with the high expression group showing lower stress ratings than lower expression groups. In line with previous research, we identified the low expression variant of the serotonin transporter gene as a risk factor for increased stress reactivity. While some dimensions of the human stress response may be stressor specific, cognitive outcomes such as working memory performance are influenced by stress in general. Different pathways of stress processing and possible underlying mechanisms are discussed.

Highlights

Stress has wide-ranging effects on our everyday lives including cognitive functioning
Using univariate ANOVAS, we looked for an effect of 5-HTTLPR/rs25531 on our main outcome, cortisol levels, and subjective VAS ratings calculated as areas under the curve (AUC; Pruessner et al 2003) to test if one subgroup is more vulnerable for acute stress (5-HTTLPR/rs25531 × condition × method)
In the ScanSTRESS group, there was a significant increase in cortisol at 15 min after stress compared to the ScanControl condition (p = 0.008)

Summary

Introduction

Stress has wide-ranging effects on our everyday lives including cognitive functioning. The experience of acute stress activates our two prominent stress-response systems, the autonomic nervous system (ANS) and the hypothalamic–pituitary–adrenal axis (HPA) (Dickerson and Kemeny 2004; Foley and Kirschbaum 2010). These systems in turn affect a wide range of cognitive domains, such as memory and attention (Shields et al 2019). Cortisol released by the HPA axis affects related brain structures such as the hippocampus and prefrontal cortex by binding to the glucocorticoid receptors (GR) and, thereby, impairing working memory performance (Arnsten 2009).

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