The Association between Genetic Variability in the NPS/NPSR1 System and Chronic Stress Responses: A Gene-Environment-(Quasi-) Experiment
Open accessAbstract
The neuropeptide S (NPS) and its receptor (NPSR1) have been implicated in stress regulation and stress-related disorders. The present study aimed at investigating the association between overall genetic variability in the NPS/NPSR1 system and psychological and cortisol stress regulation in everyday life. Our study was conceptualized as a gene-environment-(quasi-) experiment, a design that facilitates the detection of true GxE interactions. As environmental variable, we used the preparation for the first state examination for law students. In the prospective and longitudinal LawSTRESS project, students were examined at six sampling points over a 13-months period. While students who prepared for the exam and experienced long-lasting and significant stress, formed the stress group, law students experiencing usual study-related workload were assigned to the control group. As phenotypes we assessed changes over time in the cortisol awakening response (CAR; n = 176), perceived stress levels (n = 401), and anxiety symptoms (n = 397). The CAR was assessed at each sampling point immediately upon awakening and 30 as well as 45 min later. Perceived stress levels in daily life were measured by repeated ambulatory assessments and anxiety symptoms were repeatedly assessed with the anxiety subscale of the Hospital Anxiety and Depression Scale. With gene-set analyses we examined the joint association of 936 NPS/NPSR1 single nucleotide polymorphisms with the phenotypes to overcome well known limitations of candidate gene studies. As previously reported, we found a blunted CAR during the exam as well as significant increases in perceived stress levels and anxiety symptoms until the exam in the stress group, compared to the control group. The gene-set analysis did not confirm associations between genetic variability in the NPS/NPSR1 system and changes in perceived stress levels and anxiety symptoms. Regarding the CAR, we found a significant GxE interaction for the area under the curve with respect to the ground (p = .050) and a trend towards a significant effect for the area under the curve with respect to the increase (p = .054). When the analysis was restricted to the SG, associations for both CAR parameters were significant (ps < .050). This finding suggests that the association between genetic variability in the NPS/NPSR1 system and the CAR becomes visible under the environmental condition 'chronic stress exposure'. We conclude that the present study complements findings from animal models and that it provides novel evidence for a modulatory influence of the NPS/NPSR1 system on cortisol regulation in humans.
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Studies on law students found that genetic variability in the NPS/NPSR1 system becomes more evident under chronic stress conditions like exam preparation.
“Similarly, studies on law students found that genetic variability in the NPS/NPSR1 system becomes more evident under chronic stress conditions like exam preparation [17,22,41,109].”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [41]
Variants in genes like NPY, CRHR1, and 5-HTT are linked to lower resilience.
“Variants in genes like NPY, CRHR1, and 5-HTT are linked to lower resilience, while upregulation of DRD1–DRD4, DBH, DAT, and BDNF is associated with higher resilience.”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [41]
Stress resilience, the ability to manage anxiety under stress, is influenced by genetic factors.
“Stress resilience, the ability to manage anxiety under stress, is influenced by genetic factors.”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [41]
Upregulation of DRD1-DRD4, DBH, DAT, and BDNF is associated with higher resilience.
“Variants in genes like NPY, CRHR1, and 5-HTT are linked to lower resilience, while upregulation of DRD1–DRD4, DBH, DAT, and BDNF is associated with higher resilience.”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [41]
Research on medical students facing license examinations revealed significant changes in gene expression profiles in peripheral blood, validating changes in 10 key genes (DPYD, CSF3R, PLCB2, CTNNB1, PPP3CA, IRF3, POLM, CCNI, ARHGEF1, and TP53).
“Research on medical students facing license examinations revealed significant changes in gene expression profiles in peripheral blood, validating changes in 10 key genes (DPYD, CSF3R, PLCB2, CTNNB1, PPP3CA, IRF3, POLM, CCNI, ARHGEF1, and TP53).”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [41]
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- Authors
- Peter, H. L., Giglberger, M., Frank, J., Streit, F., Zänkert, S., Kreuzpointner, L., Rietschel, M., Kudielka, B. M., & Wüst, S.
- Affiliations
- University of Regensburg (DE)
- Heidelberg University (DE)
- Corresponding author
- Wüst, Stefan
- ORCID
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2022-10
- Volume
- 144
- Pages
- 105883
- ISSN
- 0306-4530 (ISSN-L)
- OpenAlex
- W4288046306
- Cited by
- 4
- References
- 55
- Citations by year
- 2024: 3 · 2023: 1
- FWCI
- 0.59
- Type
- journal article
- Language
- en
- Open access
- green
- orcid.org
- Licence
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- University of Regensburg Publication Server (University of Regensburg) (submittedVersion, cc-by-nc-nd)
- Funders
- Bundesministerium für Bildung und Forschung (01EW1810, 01EW1904)
- Universität Regensburg
- Deutsche Forschungsgemeinschaft (WU392/9-1)
- Forskningsrådet för Arbetsliv och Socialvetenskap
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- neuropeptide S, NPSR1, gene-environment interaction, chronic stress, cortisol awakening response, perceived stress, anxiety symptoms, law students, gene set analysis, single nucleotide polymorphisms, cortisol regulation, stress-related disorders, ambulatory assessment
- MeSH terms
- Animals, Anxiety, Humans, Hydrocortisone, Neuropeptides, Prospective Studies, Polymorphism, Single Nucleotide, Receptors, G-Protein-Coupled
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