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Links Between Stress, Sleep, and Inflammation: Are there Sex Differences?

  • Sex and Gender Issues in Behavioral Health (CN Epperson and L Hantsoo, Section Editors)
  • Published:
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Abstract

Purpose of Review

Inflammation has emerged as an important biological process in the development of many age-related diseases that occur at different frequencies in men and women. The aim of this review was to examine the current evidence linking stress and sleep with inflammation with a focus on sex differences.

Recent Findings

Psychosocial stress that occurs either acutely or chronically is associated with elevated levels of systemic inflammation. While not as robust, insufficient sleep, particularly sleep disturbances, appears to be associated with higher levels of inflammatory activity as well. In several contexts, associations of stress and insufficient sleep with inflammation appear stronger in women than in men. However, this should be interpreted with caution as few studies test for sex differences.

Summary

Stress and poor sleep often predict elevations in systemic inflammation. While there is some evidence that these associations are stronger in women, findings are largely mixed and more systematic investigations of sex differences in future studies are warranted.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Scrivo R, Vasile M, Bartosiewicz I, Valesini G. Inflammation as “common soil” of the multifactorial diseases. Autoimmun Rev. 2011;10(7):369–74. https://doi.org/10.1016/j.autrev.2010.12.006.

    Article  PubMed  Google Scholar 

  2. Hunter TM, Boytsov NN, Zhang X, Schroeder K, Michaud K, Araujo AB. Prevalence of rheumatoid arthritis in the United States adult population in healthcare claims databases, 2004-2014. Rheumatol Int. 2017;37(9):1551–7. https://doi.org/10.1007/s00296-017-3726-1.

    Article  PubMed  Google Scholar 

  3. Miller AH, Raison CL. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol. 2016;16(1):22–34. https://doi.org/10.1038/nri.2015.5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Salk RH, Hyde JS, Abramson LY. Gender differences in depression in representative national samples: meta-analyses of diagnoses and symptoms. Psychol Bull. 2017;143(8):783–822. https://doi.org/10.1037/bul0000102.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Mikkola TS, Gissler M, Merikukka M, Tuomikoski P, Ylikorkala O. Sex differences in age-related cardiovascular mortality. PLoS One. 2013;8(5):e63347. https://doi.org/10.1371/journal.pone.0063347.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. • Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol. 2016;16(10):626–38. https://doi.org/10.1038/nri.2016.90 This paper reviews sex differences in immune responses including inflammation.

    Article  CAS  PubMed  Google Scholar 

  7. Rainville JR, Tsyglakova M, Hodes GE. Deciphering sex differences in the immune system and depression. Front Neuroendocrinol. 2017;50:67–90. https://doi.org/10.1016/j.yfrne.2017.12.004.

    Article  CAS  PubMed  Google Scholar 

  8. Bekhbat M, Neigh GN. Sex differences in the neuro-immune consequences of stress: focus on depression and anxiety. Brain Behav Immun. 2018;67:1–12. https://doi.org/10.1016/j.bbi.2017.02.006.

    Article  PubMed  Google Scholar 

  9. Duma D, Collins JB, Chou JW, Cidlowski JA. Sexually dimorphic actions of glucocorticoids provide a link to inflammatory diseases with gender differences in prevalence. Sci Signal. 2010;3(143):ra74. https://doi.org/10.1126/scisignal.2001077.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Deak T, Quinn M, Cidlowski JA, Victoria NC, Murphy AZ, Sheridan JF. Neuroimmune mechanisms of stress: sex differences, developmental plasticity, and implications for pharmacotherapy of stress-related disease. Stress. 2015;18(4):367–80. https://doi.org/10.3109/10253890.2015.1053451.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. • Epel ES, Crosswell AD, Mayer SE, Prather AA, Slavich GM, Puterman E, et al. More than a feeling: a unified view of stress measurement for population science. Front Neuroendocrinol. 2018;49:146–69. https://doi.org/10.1016/j.yfrne.2018.03.001 This review provides a contemporary theoretical perspective on stress and stress measurement.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Cohen S, Murphy MLM, Prather AA. Ten surprising facts about stressful life events and disease risk. Annu Rev Psychol. 2018;70:577–97. https://doi.org/10.1146/annurev-psych-010418-102857.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Miller GE, Chen E, Parker KJ. Psychological stress in childhood and susceptibility to the chronic diseases of aging: moving toward a model of behavioral and biological mechanisms. Psychol Bull. 2011;137(6):959–97. https://doi.org/10.1037/a0024768.

    Article  PubMed  PubMed Central  Google Scholar 

  14. • Baumeister D, Akhtar R, Ciufolini S, Pariante CM, Mondelli V. Childhood trauma and adulthood inflammation: a meta-analysis of peripheral C-reactive protein, interleukin-6 and tumour necrosis factor-alpha. Mol Psychiatry. 2016;21(5):642–9. https://doi.org/10.1038/mp.2015.67 This paper provides a meta-analytic review of the data linking early life trauma and inflammation.

    Article  CAS  PubMed  Google Scholar 

  15. Baldwin JR, Arseneault L, Caspi A, Fisher HL, Moffitt TE, Odgers CL, et al. Childhood victimization and inflammation in young adulthood: a genetically sensitive cohort study. Brain Behav Immun. 2018;67:211–7. https://doi.org/10.1016/j.bbi.2017.08.025.

    Article  PubMed  PubMed Central  Google Scholar 

  16. • Marsland AL, Walsh C, Lockwood K, John-Henderson NA. The effects of acute psychological stress on circulating and stimulated inflammatory markers: a systematic review and meta-analysis. Brain Behav Immun. 2017;64:208–19. https://doi.org/10.1016/j.bbi.2017.01.011 This paper provides a meta-analytic review of the human literature on acute stress and markers of inflammation.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Prather AA, Carroll JE, Fury JM, McDade KK, Ross D, Marsland AL. Gender differences in stimulated cytokine production following acute psychological stress. Brain Behav Immun. 2009;23(5):622–8. https://doi.org/10.1016/j.bbi.2008.11.004.

    Article  CAS  PubMed  Google Scholar 

  18. • Lockwood KG, Marsland AL, Cohen S, Gianaros PJ. Sex differences in the association between stressor-evoked interleukin-6 reactivity and C-reactive protein. Brain Behav Immun. 2016;58:173–80. https://doi.org/10.1016/j.bbi.2016.07.001 This study demonstrates sex differences in levels of IL-6 in response to acute laboratory stress.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hackett RA, Hamer M, Endrighi R, Brydon L, Steptoe A. Loneliness and stress-related inflammatory and neuroendocrine responses in older men and women. Psychoneuroendocrinology. 2012;37(11):1801–9. https://doi.org/10.1016/j.psyneuen.2012.03.016.

    Article  CAS  PubMed  Google Scholar 

  20. Steptoe A, Owen N, Kunz-Ebrecht S, Mohamed-Ali V. Inflammatory cytokines, socioeconomic status, and acute stress responsivity. Brain Behav Immun. 2002;16(6):774–84.

    Article  CAS  PubMed  Google Scholar 

  21. Chiang JJ, Turiano NA, Mroczek DK, Miller GE. Affective reactivity to daily stress and 20-year mortality risk in adults with chronic illness: findings from the National Study of Daily Experiences. Health Psychol. 2018;37(2):170–8. https://doi.org/10.1037/hea0000567.

    Article  PubMed  Google Scholar 

  22. Sin NL, Graham-Engeland JE, Ong AD, Almeida DM. Affective reactivity to daily stressors is associated with elevated inflammation. Health Psychol. 2015;34(12):1154–65. https://doi.org/10.1037/hea0000240.

    Article  PubMed  PubMed Central  Google Scholar 

  23. • Irwin MR, Olmstead R, Carroll JE. Sleep disturbance, sleep duration, and inflammation: a systematic review and meta-analysis of cohort studies and experimental sleep deprivation. Biol Psychiatry. 2015. https://doi.org/10.1016/j.biopsych.2015.05.014 This paper provides a meta-analytic review of the literature linking sleep and inflammation.

  24. Nowakowski S, Matthews KA, von Kanel R, Hall MH, Thurston RC. Sleep characteristics and inflammatory biomarkers among midlife women. Sleep. 2018;41(5). https://doi.org/10.1093/sleep/zsy049.

  25. Drake CL, Pillai V, Roth T. Stress and sleep reactivity: a prospective investigation of the stress-diathesis model of insomnia. Sleep. 2014;37(8):1295–304. https://doi.org/10.5665/sleep.3916.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Drake CL, Roehrs T, Roth T. Insomnia causes, consequences, and therapeutics: an overview. Depress Anxiety. 2003;18(4):163–76. https://doi.org/10.1002/da.10151.

    Article  PubMed  Google Scholar 

  27. • Gordon AM, Mendes WB, Prather AA. The social side of sleep: elucidating the links between sleep and social processes. Curr Dir Psychol Sci. 2017;26(5):470–5. https://doi.org/10.1177/0963721417712269 This review discusses the bidirectional links between sleep and social processes including social stress.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Irwin MR, Witarama T, Caudill M, Olmstead R, Breen EC. Sleep loss activates cellular inflammation and signal transducer and activator of transcription (STAT) family proteins in humans. Brain Behav Immun. 2015;47:86–92. https://doi.org/10.1016/j.bbi.2014.09.017.

    Article  CAS  PubMed  Google Scholar 

  29. Irwin M, Wang M, Campomayor CO, Collado-Hidalgo A, Cole S. Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammation. Arch Intern Med. 2006;166(16):1756–62. https://doi.org/10.1001/archinte.166.16.1756.

    Article  CAS  PubMed  Google Scholar 

  30. Carroll JE, Carrillo C, Olmstead R, Witarama T, Breen EC, Yokomizo M, et al. Sleep deprivation and divergent toll-like receptor-4 activation of cellular inflammation in aging. Sleep. 2015;38(2):205–11. https://doi.org/10.5665/sleep.4398.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Irwin MR, Wang M, Ribeiro D, Cho HJ, Olmstead R, Breen EC, et al. Sleep loss activates cellular inflammatory signaling. Biol Psychiatry. 2008;64(6):538–40. https://doi.org/10.1016/j.biopsych.2008.05.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Bixler EO, Papaliaga MN, Vgontzas AN, Lin HM, Pejovic S, Karataraki M, et al. Women sleep objectively better than men and the sleep of young women is more resilient to external stressors: effects of age and menopause. J Sleep Res. 2009;18(2):221–8. https://doi.org/10.1111/j.1365-2869.2008.00713.x.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Lindberg E, Janson C, Gislason T, Bjornsson E, Hetta J, Boman G. Sleep disturbances in a young adult population: can gender differences be explained by differences in psychological status? Sleep. 1997;20(6):381–7.

    Article  CAS  PubMed  Google Scholar 

  34. Goel N, Kim H, Lao RP. Gender differences in polysomnographic sleep in young healthy sleepers. Chronobiol Int. 2005;22(5):905–15. https://doi.org/10.1080/07420520500263235.

    Article  PubMed  Google Scholar 

  35. Krishnan V, Collop NA. Gender differences in sleep disorders. Curr Opin Pulm Med. 2006;12(6):383–9. https://doi.org/10.1097/01.mcp.0000245705.69440.6a.

    Article  PubMed  Google Scholar 

  36. Mong JA, Cusmano DM. Sex differences in sleep: impact of biological sex and sex steroids. Philosophical transactions of the Royal Society of London Series B, Biological sciences. 2016;371(1688):20150110. https://doi.org/10.1098/rstb.2015.0110.

  37. Zhang B, Wing YK. Sex differences in insomnia: a meta-analysis. Sleep. 2006;29(1):85–93.

    Article  PubMed  Google Scholar 

  38. Bakour C, Schwartz S, O'Rourke K, Wang W, Sappenfield W, Couluris M et al. Sleep duration trajectories and systemic inflammation in young adults: results from the National Longitudinal Study of Adolescent to Adult Health (Add Health). Sleep. 2017;40(11). doi:https://doi.org/10.1093/sleep/zsx156.

  39. Kim TH, Carroll JE, An SK, Seeman TE, Namkoong K, Lee E. Associations between actigraphy-assessed sleep, inflammatory markers, and insulin resistance in the Midlife Development in the United States (MIDUS) study. Sleep Med. 2016;27–28:72–9. https://doi.org/10.1016/j.sleep.2016.07.023.

    Article  PubMed  PubMed Central  Google Scholar 

  40. • Prather AA, Epel ES, Cohen BE, Neylan TC, Whooley MA. Gender differences in the prospective associations of self-reported sleep quality with biomarkers of systemic inflammation and coagulation: findings from the Heart and Soul Study. J Psychiatr Res. 2013;47(9):1228–35. https://doi.org/10.1016/j.jpsychires.2013.05.004 This study shows that poor sleep quality prospectively predicts levels of inflammation in women but not in men.

    Article  PubMed  Google Scholar 

  41. Suarez EC. Self-reported symptoms of sleep disturbance and inflammation, coagulation, insulin resistance and psychosocial distress: evidence for gender disparity. Brain Behav Immun. 2008;22(6):960–8. https://doi.org/10.1016/j.bbi.2008.01.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Miller MA, Kandala NB, Kivimaki M, Kumari M, Brunner EJ, Lowe GD, et al. Gender differences in the cross-sectional relationships between sleep duration and markers of inflammation: Whitehall II study. Sleep. 2009;32(7):857–64.

    PubMed  PubMed Central  Google Scholar 

  43. Kravitz HM, Zhao X, Bromberger JT, Gold EB, Hall MH, Matthews KA, et al. Sleep disturbance during the menopausal transition in a multi-ethnic community sample of women. Sleep. 2008;31(7):979–90.

    PubMed  PubMed Central  Google Scholar 

  44. Mong JA, Baker FC, Mahoney MM, Paul KN, Schwartz MD, Semba K, et al. Sleep, rhythms, and the endocrine brain: influence of sex and gonadal hormones. J Neurosci. 2011;31(45):16107–16. https://doi.org/10.1523/JNEUROSCI.4175-11.2011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. • Bale TL, Epperson CN. Sex differences and stress across the lifespan. Nat Neurosci. 2015;18(10):1413–20. https://doi.org/10.1038/nn.4112 This review discusses the neurobiological differences between men and women in response to stress.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Mazure CM, Jones DP. Twenty years and still counting: including women as participants and studying sex and gender in biomedical research. BMC Womens Health. 2015;15:94. https://doi.org/10.1186/s12905-015-0251-9.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Institue of Medicine. Sex Differences and Implications for Translational Neuroscience Research: Workshop Summary. Washington, DC: National Academies Press; 2011.

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Funding

This work was supported by the NIH funding R24AG048024 (ADC, AAP), K01AG057859 (ADC), and R01HL142051 (AAP) and a predoctoral training fellowship T32MH020006 for MRD.

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Authors and Affiliations

  1. University of California, Berkeley, CA, USA

    Emily A. Dolsen

  2. Center for Health and Community, Department of Psychiatry, University of California, San Francisco, CA, USA

    Alexandra D. Crosswell & Aric A. Prather

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  1. Emily A. Dolsen
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Correspondence to Aric A. Prather.

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Dolsen, E.A., Crosswell, A.D. & Prather, A.A. Links Between Stress, Sleep, and Inflammation: Are there Sex Differences?. Curr Psychiatry Rep 21, 8 (2019). https://doi.org/10.1007/s11920-019-0993-4

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