心理ストレスのバイオマーカーに関する最近の研究動向

Perplexity曰く

Based on the recent literature, there have been several advancements in biomarkers for psychological stress:

1. Cortisol remains a key biomarker, with new developments in detection methods:

– Wearable, flexible devices for real-time, continuous cortisol monitoring in sweat have been developed[6].
– Electrochemical biosensors enable rapid, real-time detection of cortisol in biofluids[8].
– Salivary cortisol sensing is being integrated into smart dentures and braces for ambulatory monitoring[7].

2. Multi-biomarker approaches:

– Allostatic load, which measures cumulative biological burden across multiple systems, is being used as a comprehensive stress biomarker[5].
– Combinations of biomarkers like cortisol, α-amylase, chromogranin A, brain-derived neurotrophic factor, and immunoglobulin A in saliva are being studied[7].

3. Genetic and molecular biomarkers:

– FKBP5 gene expression has emerged as a top biomarker for stress disorders[1].
– MicroRNAs and long non-coding RNAs are being explored as potential stress biomarkers[2].

4. Immune system markers:

– C-reactive protein (CRP) and interleukins 6 and 8 have shown promise as diagnostic biomarkers of chronic stress[3].
– Changes in natural killer (NK) cell activity are being investigated[3].

5. Metabolic biomarkers:

– Glucose, HbA1c, triglycerides, and cholesterol levels are being studied in relation to chronic stress[3].

6. Oxidative stress markers:

– Malondialdehyde and isoprostanes are being examined as indicators of stress-induced oxidative damage[2].

7. Advanced detection technologies:

– Surface plasmon resonance sensing and molecular imprinted polymers offer sensitive cortisol detection[7].
– Integration of aptamers with electrochemiluminescence biosensing provides label-free, cost-effective approaches[7].

These advancements are moving towards more comprehensive, real-time, and non-invasive methods of stress assessment, with potential applications in personalized stress management and health monitoring.

Citations:
[1] https://www.nature.com/articles/s41380-019-0370-z
[2] https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2019.00091/full
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434839/
[4] https://academic.oup.com/psychsocgerontology/article/65B/5/513/619179
[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2841407/
[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492543/
[7] https://pubs.rsc.org/en/content/articlelanding/2024/ma/d3ma00937h
[8] https://pubmed.ncbi.nlm.nih.gov/37989847/

Based on the search results, here are some relevant review articles on biomarkers for psychological stress from Cell Press journals:

## Neuron: A Neural Biomarker of Psychological Vulnerability to Future Life Stress

This study demonstrated that individual differences in threat-related amygdala reactivity can predict psychological vulnerability to life stress occurring 1 to 4 years in the future[6]. The researchers found that heightened amygdala reactivity to threat was associated with greater susceptibility to stress-related mental health problems like depression and anxiety when exposed to major life stressors. This suggests amygdala reactivity could serve as a neural biomarker to identify those at higher risk of developing stress-related psychopathology.

## Immunity: The Gut Microbiome Regulates Psychological-Stress-Induced Inflammation

This review article explored how psychological stress impacts inflammation through interactions with the gut microbiome[7]. The researchers found that stress promotes vascular occlusive events (VOEs) by eliciting a glucocorticoid hormonal response that increases gut permeability. This leads to microbiota-dependent interleukin production, highlighting the gut microbiome’s role in mediating stress-induced inflammatory responses. The findings suggest gut microbiome composition and function could potentially serve as biomarkers of stress vulnerability.

## Key Points:

– Threat-related amygdala reactivity may predict future stress vulnerability
– Gut microbiome regulates stress-induced inflammation
– Stress increases gut permeability and microbiota-dependent cytokine production
– Gut microbiome markers could indicate stress susceptibility

These Cell Press reviews provide insight into both neural and gut microbiome-based biomarkers that may help identify individuals at higher risk of adverse health effects from psychological stress. The findings point to promising avenues for developing predictive biomarkers of stress vulnerability, which could enable earlier interventions for at-risk individuals.

Citations:
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2841407/
[2] https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2019.00091/full
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434839/
[4] https://academic.oup.com/psychsocgerontology/article/65B/5/513/619179
[5] https://www.nature.com/articles/s41380-019-0370-z
[6] https://www.cell.com/neuron/fulltext/S0896-6273%2814%2901164-7
[7] https://www.cell.com/immunity/fulltext/S1074-7613%2820%2930280-6
[8] https://www.sciencedirect.com/science/article/pii/S0022395624003406

Consensus曰く

1. Giannakakis, G., Grigoriadis, D., Giannakaki, K., Simantiraki, O., Roniotis, A., & Tsiknakis, M. (2019). Review on Psychological Stress Detection Using Biosignals. IEEE Transactions on Affective Computing, 13, 440-460. https://doi.org/10.1109/TAFFC.2019.2927337.　Psychological stress is effectively detected using biosignals, with this paper providing guidelines for efficient detection and enhancing the reliability of biosignal data features.
2. Chojnowska, S., Ptaszyńska-Sarosiek, I., Kępka, A., Knaś, M., & Waszkiewicz, N. (2021). Salivary Biomarkers of Stress, Anxiety and Depression. Journal of Clinical Medicine, 10. https://doi.org/10.3390/jcm10030517.　Salivary biomarkers, such as cortisol, lysozyme, sAA, and CgA, show promise in quick diagnosis and monitoring of stress, anxiety, and depression, potentially aiding in pharmacological treatment monitoring.
3. Dhama, K., Latheef, S., Dadar, M., Samad, H., Munjal, A., Khandia, R., Karthik, K., Tiwari, R., Yatoo, M., Bhatt, P., Chakraborty, S., Singh, K., Iqbal, H., Chaicumpa, W., & Joshi, S. (2019). Biomarkers in Stress Related Diseases/Disorders: Diagnostic, Prognostic, and Therapeutic Values. Frontiers in Molecular Biosciences, 6. https://doi.org/10.3389/fmolb.2019.00091.　　Stress biomarkers can help monitor stress levels, aid in prognosis, and guide therapy for stress-related diseases and disorders.
4. Le-Niculescu, H., Roseberry, K., Levey, D., Rogers, J., Kosary, K., Prabha, S., Jones, T., Judd, S., McCormick, M., Wessel, A., Williams, A., Phalen, P., Mamdani, F., Sequeira, A., Kurian, S., & Niculescu, A. (2019). Towards precision medicine for stress disorders: diagnostic biomarkers and targeted drugs. Molecular Psychiatry, 25, 918 – 938. https://doi.org/10.1038/s41380-019-0370-z.　This study identified blood gene expression biomarkers that can predict psychological stress and future psychiatric hospitalizations, potentially improving diagnosis and treatment for stress disorders like PTSD.
5. An, K., Salyer, J., Brown, R., Kao, H., Starkweather, A., & Shim, I. (2016). Salivary Biomarkers of Chronic Psychosocial Stress and CVD Risks. Biological Research For Nursing, 18, 241 – 263. https://doi.org/10.1177/1099800415604437.　Salivary biomarkers, particularly cortisol, have been useful in stress research, particularly when linked to cardiovascular disease risks.
6. McEwen, B. (2015). Biomarkers for assessing population and individual health and disease related to stress and adaptation.. Metabolism: clinical and experimental, 64 3 Suppl 1, S2-S10 . https://doi.org/10.1016/j.metabol.2014.10.029.　Biomarkers play a crucial role in stress biology, assessing individual and population health and predicting disease risk, with potential for predictive biomarkers for suicidal depression.
7. Labad, J., Stojanovic-Pérez, A., Montalvo, I., Solé, M., Cabezas, Á., Ortega, L., Moreno, I., Vilella, E., Martorell, L., Reynolds, R., & Gutiérrez-Zotes, A. (2015). Corrigendum to “Stress biomarkers as predictors of transition to psychosis in at-risk mental states: Roles for cortisol, prolactin and albumin” [J. Psychiatr. Res. 60 (2015) 163–169]. Journal of Psychiatric Research, 62, 138. https://doi.org/10.1016/J.JPSYCHIRES.2015.01.012.　Cortisol, prolactin, and albumin are key stress biomarkers that predict the transition to psychosis in at-risk mental states.
8. Labad, J., Stojanovic-Pérez, A., Montalvo, I., Solé, M., Cabezas, Á., Ortega, L., Moreno, I., Vilella, E., Martorell, L., Reynolds, R., & Gutiérrez-Zotes, A. (2015). Stress biomarkers as predictors of transition to psychosis in at-risk mental states: roles for cortisol, prolactin and albumin.. Journal of psychiatric research, 60, 163-9 . https://doi.org/10.1016/j.jpsychires.2014.10.011.　Prolactin levels are a predictor of psychosis transition in individuals with at-risk mental states, while albumin levels have a protective effect.
9. Batista, P., Pereira, A., & Vaz, A. (2017). Salivary Biomarkers in Psychological Stress Diagnosis. , 3, 9-18. https://doi.org/10.20431/2455-1538.0302002.　Salivary cortisol and alpha-amylase biomarkers are the most used in diagnosing psychological stress, providing valuable information for understanding diseases and their responses to treatment.
10. Ockenburg, S., Booij, S., Riese, H., Rosmalen, J., & Janssens, K. (2015). How to assess stress biomarkers for idiographic research?. Psychoneuroendocrinology, 62, 189-199. https://doi.org/10.1016/j.psyneuen.2015.08.002.　Idiographic research, using various matrices and new collection tools, can provide promising new insights into the association between stress biomarkers and psychological or somatic symptoms.

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