Gen-Umwelt-Interaktionseffekte auf die Stressreaktivität im Menschen mit Hinblick auf neuronale Netzwerke, kritische Lebensereignisse und molekulare Mechanismen
Zusammenfassung der Projektergebnisse
In this study, we employed two stress tests – the TSST (Trier Social Stress Test), an acute behavioral stress test, and the MIST (Montreal Imaging Stress Test), a paradigm that is designed to arouse stress in the scanner. Both paradigms were used to induce psychosocial stress in healthy adults. Additionally, a number of questionnaires, a life events interview, and several collections of blood and saliva samples were administered. Aim of these studies was to investigate psychobiological processes of stress with regard to brain function (regions of interest as), genetic (candidate gene association approach and epigenetic markers) and environmental influences (especially early life stress) in healthy adults. First results of the imaging study (MIST) promisingly point in the right direction yet further data is needed in order to run in-depth analyses and outline compelling conclusions. The MIST induced a significant stress response in a subsample of subjects, called the responders. Direct comparison between brain activity changes in responders vs. non-responders, in response to challenging math, revealed increased activity in a priori brain areas such as the prefrontal cortex (PFC). Different research from other labs that pay attention to genetics and behavior, focus of our studies has shifted from single-gene explanations and polymorphisms to a much more comprehensive analysis of gene regulatory mechanisms. The MIST study represents a critical first step in examining the relations among neural activity and stress reactivity. Investigating individual differences in stress reactivity has the potential to provide important insights into an individual’s vulnerability to experience stressful episodes and in addition, the impact of social, personality and genetic determinants. As expected, the TSST led to a significant increase in the endocrine stress response. However, results demonstrate a dissociation of different stress responses with a subgroup showing a diminished increase in cortisol (non responder group). The application of the state-of-the-art TSST paradigm integrates stress hormone analysis with extensive behavioral phenotyping and blood draws at multiple time points to assess the time course of gene expression during stressful social interactions is a very unique design which, to our knowledge, has never been tested before. These changes in the expression level of specific miRNAs in the subgroup of responders might not only have implications for the pathophysiology of the individual stress response and therefore clinical implications but also provide as empirical source of non-invasive biomarkers for negative health outcomes such as depression, heart diseases, and cancer. Since a specific miRNA might be involved in the corresponding regulation of protein expression in several functional networks, this kind of biomarkers might contribute to new development of target therapeutic intervention in near future. Further studies are required to examine changes in miRNA expression for the acute stress response more closely and to investigate the role of this biomarker in the development of chronic diseases. In the long run, this knowledge might be helpful for improving diagnostics and developing therapeutic manuals. These multidisciplinary approaches will eventually allow the formulation of a more comprehensive framework of functional neuroanatomy of cortisol regulation and changes in gene expression and furthermore, will give directions in the field of plasticity and resilience research.
Projektbezogene Publikationen (Auswahl)
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Neural and endocrine activity in response to an acute psychosocial stressor. Poster 195.22/VV70 presented at 41ist Annual Meeting of the Society for Neuroscience (SfN), Washington, D.C., USA
Mueller, A., Ferri, J. and Canli, T.
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MicroRNA Profiling of the Human Stress Response. Poster presented at 42nd Annual Meeting of the International Society of Psychoneuroendocrinology (ISPNE), New York, USA.
Mueller, A., Jurkiewicz, M., Ferri, J., Izzi, S., Johns, C., Wu, X., Stone, A.A., Canli, T.
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Serotonin Transporter Gene. Encyclopedia of Behavioral Medicine,
ed.: Marc D. Gellman, J. Rick Turner. 2013, pp 1769-1772.
Mueller, A., Canli, T.
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Einfluss von MicroRNA auf die Stressantwort im Menschen. 40. Tagung „Psychologie und Gehirn“, Lübeck, Germany, 2014.
Jurkiewicz, M., Mueller-Alcazar, A., Moser, D., Jayatilaka, I., Mikhailik, A., Ferri, J., Wu, X., Litcher-Kelly, L., Stone, A., Canli, T.
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Stressing over anxiety: A novel interaction of 5-HTTLPR and anxiety-related phenotypes in older adults. Psychoneuroendocrinology, Vol. 71. 2016, pp. 36-42.
Fogelman, N., Mikhailik, A., Mueller-Alcazar, A., Bernard, K., Canli, T.
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Integrated microRNA and mRNA gene expression in peripheral blood mononuclear cells in response to acute psychosocial stress: a repeated-measures within-subject pilot study. BMC Research Notes, Vol. 14. 2021, Article number: 222.
Jurkiewicz M.M., Mueller-Alcazar A., Moser D.A., et al.
