Table Info

Table 6.

Summary of stressor correlations to MS outcomes

MS clinical feature outcomes	Predictor blocks included in final model	Additional significant individual stressor contributions to MS outcomes
Pain interference	Child & adult stressors
Fatigue	Child stressors	Childhood stress severity related to: reporting any fatigue & magnitude of fatigue Child stress count related to the magnitude of fatigue
Psychiatric morbidity	Child & adult stressors	Adult stress severity

Blank cell indicates model level significance and no additional individual level contributions

Declarations

Acknowledgments

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of Duke CTSI or the VA.

Author contributions

CSP: Conceptualization, Formal analysis, Writing—original draft. TJB: Conceptualization, Resources, Writing—review & editing. RPS: Conceptualization, Formal analysis, Writing—review & editing. CMC: Conceptualization, Writing—review & editing. AW: Writing—review & editing. SAS: Conceptualization, Supervision, Writing—review & editing.

Conflicts of interest

The authors have no conflicts of interest to declare.

Ethical approval

This study was approved by the University of Michigan IRB (HUM00200716).

Consent to participate

Participants read informed consent materials during the screening process and agreed to an implied consent statement to proceed with the study.

Consent to publication

Not applicable.

Availability of data and materials

Data is available upon request to corresponding author or Harvard Dataverse repository.

Funding

CSP was supported by NIH/NINR grant [T32NR016914], “Complexity: Innovations for Promoting Health and Safety”, Rackham Graduate School, Duke Clinical and Translational Science Institute (CTSI), and Durham VA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

References

Felitti VJ, Anda RF, Nordenberg D, Williamson DF, Spitz AM, Edwards V, et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The Adverse Childhood Experiences (ACE) Study. Am J Prev Med. 1998;14:245–58. [DOI] [PubMed]

Dube SR, Fairweather D, Pearson WS, Felitti VJ, Anda RF, Croft JB. Cumulative childhood stress and autoimmune diseases in adults. Psychosom Med. 2009;71:243–50. [DOI] [PubMed] [PMC]

Grummitt LR, Kreski NT, Kim SG, Platt J, Keyes KM, McLaughlin KA. Association of childhood adversity with morbidity and mortality in US adults: a systematic review. JAMA Pediatr. 2021;175:1269–78. [DOI] [PubMed] [PMC]

Eid K, Torkildsen Ø, Aarseth J, Aalstad M, Bhan A, Celius EG, et al. Association of adverse childhood experiences with the development of multiple sclerosis. J Neurol Neurosurg Psychiatry. 2022;93:645–50. [DOI] [PubMed] [PMC]

Polick CS, Polick SR, Stoddard SA. Relationships between childhood trauma and multiple sclerosis: a systematic review. J Psychosom Res. 2022;160:110981. [DOI] [PubMed]

Pust GEA, Dettmers C, Randerath J, Rahn AC, Heesen C, Schmidt R, et al. Fatigue in multiple sclerosis is associated with childhood adversities. Front Psychiatry. 2020;11:811. [DOI] [PubMed] [PMC]

Polick CS, Ploutz-Snyder R, Braley TJ, Connell CM, Stoddard SA. Fatigue, pain interference, and psychiatric morbidity in multiple sclerosis: the role of childhood stress. PLoS One. 2023;18:e0292233. [DOI] [PubMed] [PMC]

MacDonald TM, Fisk JD, Bernstein CN, El-Gabalawy R, Hitchon CA, Kornelsen J, et al. The association between childhood maltreatment and pain catastrophizing in individuals with immune-mediated inflammatory diseases. J Psychosom Res. 2021;145:110479. [DOI] [PubMed]

Eilam-Stock T, Links J, Khan NZ, Bacon TE, Zuniga G, Laing L, et al. Adverse childhood experiences predict reaction to multiple sclerosis diagnosis. Health Psychol Open. 2021;8:20551029211052830. [DOI] [PubMed] [PMC]

10.

Wan A, Bernstein CN, Graff LA, Patten SB, Sareen J, Fisk JD, et al.; CIHR Team in Defining the Burden and Managing the Effects of Immune-mediated Inflammatory Disease. Childhood maltreatment and psychiatric comorbidity in immune-mediated inflammatory disorders. Psychosom Med. 2022;84:10–9. [DOI] [PubMed]

11.

The effects of adverse childhood experiences and childhood socioeconomic disadvantage on adolescent depression and suicidality: a scoping review protocol [Internet]. Ann Arbor (MI): University of Michigan; c2024 [cited 2022 May 24]. Available from: https://deepblue.lib.umich.edu/handle/2027.42/172501

12.

Slavich GM, Shields GS. Assessing lifetime stress exposure using the Stress and Adversity Inventory for Adults (Adult STRAIN): an overview and initial validation. Psychosom Med. 2018;80:17–27. [DOI] [PubMed] [PMC]

13.

Albott CS, Forbes MK, Anker JJ. Association of childhood adversity with differential susceptibility of transdiagnostic psychopathology to environmental stress in adulthood. JAMA Netw Open. 2018;1:e185354. [DOI] [PubMed] [PMC]

14.

Polick CS, Ploutz-Snyder R, Braley TJ, Connell CM, Stoddard SA. Associations among stressors across the lifespan, disability, and relapses in adults with multiple sclerosis. Brain Behav. 2023;13:e3073. [DOI] [PubMed] [PMC]

15.

von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies. Int J Surg. 2014;12:1495–9. [DOI] [PubMed]

16.

Amtmann D, Cook KF, Jensen MP, Chen WH, Choi S, Revicki D, et al. Development of a PROMIS item bank to measure pain interference. Pain. 2010;150:173–82. [DOI] [PubMed] [PMC]

17.

Braley TJ, Whibley D, Alschuler KN, Ehde DM, Chervin RD, Clauw DJ, et al. Cannabinoid use among Americans with MS: current trends and gaps in knowledge. Mult Scler J Exp Transl Clin. 2020;6:2055217320959816. [DOI] [PubMed] [PMC]

18.

Cook KF, Bamer AM, Roddey TS, Kraft GH, Kim J, Amtmann D. A PROMIS fatigue short form for use by individuals who have multiple sclerosis. Qual Life Res. 2012;21:1021–30. [DOI] [PubMed] [PMC]

19.

Senders A, Hanes D, Bourdette D, Whitham R, Shinto L. Reducing survey burden: feasibility and validity of PROMIS measures in multiple sclerosis. Mult Scler. 2014;20:1102–11. [DOI] [PubMed] [PMC]

20.

Amezcua L, Rivera VM, Vazquez TC, Baezconde-Garbanati L, Langer-Gould A. Health disparities, inequities, and social determinants of health in multiple sclerosis and related disorders in the US: a review. JAMA Neurol. 2021;78:1515–24. [DOI] [PubMed]

21.

Amezcua L, McCauley JL. Race and ethnicity on MS presentation and disease course. Mult Scler. 2020;26:561–7. [DOI] [PubMed] [PMC]

22.

Marrie RA, Leung S, Tyry T, Cutter GR, Fox R, Salter A. Use of eHealth and mHealth technology by persons with multiple sclerosis. Mult Scler Relat Disord. 2019;27:13–9. [DOI] [PubMed]

23.

Who gets MS? [Internet]. Waltham (MA): National Multiple Sclerosis Society; c2024 [cited 2023 Nov 6]. Available from: https://www.nationalmssociety.org/What-is-MS/Who-Gets-MS

24.

Cella D, Riley W, Stone A, Rothrock N, Reeve B, Yount S, et al.; PROMIS Cooperative Group. The Patient-Reported Outcomes Measurement Information System (PROMIS) developed and tested its first wave of adult self-reported health outcome item banks: 2005–2008. J Clin Epidemiol. 2010;63:1179–94. [DOI] [PubMed] [PMC]

25.

Jiang J, Abduljabbar S, Zhang C, Osier N. The relationship between stress and disease onset and relapse in multiple sclerosis: a systematic review. Mult Scler Relat Disord. 2022;67:104142. [DOI] [PubMed]

26.

Artemiadis AK, Anagnostouli MC, Alexopoulos EC. Stress as a risk factor for multiple sclerosis onset or relapse: a systematic review. Neuroepidemiology. 2011;36:109–20. [DOI] [PubMed]

27.

Swanepoel I, van Staden W, Fletcher L. Psychological resilience and vulnerability as mediators between adverse life events and fatigue, motor dysfunction, and paresthesia in multiple sclerosis. Psychosom Med. 2020;82:138–46. [DOI] [PubMed]

28.

Okai AF, Howard AM, Williams MJ, Brink JD, Chen C, Stuchiner TL, et al. Advancing care and outcomes for African American patients with multiple sclerosis. Neurology. 2022;98:1015–20. [DOI] [PubMed] [PMC]

29.

Simpson R, Simpson S, Ramparsad N, Lawrence M, Booth J, Mercer SW. Mindfulness-based interventions for mental well-being among people with multiple sclerosis: a systematic review and meta-analysis of randomised controlled trials. J Neurol Neurosurg Psychiatry. 2019;90:1051–8. [DOI] [PubMed]

30.

Braley TJ, Alschuler K, Ehde D, Little R, von Geldern G, Chervin RD, et al. A comparative effectiveness trial of telephone-delivered cognitive behavioral therapy, modafinil, and combination therapy of both interventions for fatigue in multiple sclerosis: primary results from the COMBO-MS trial. ACTRIMS 2023: Proceedings of the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum; 2023 Feb 23–25; San Diego, CA, US. SAGE Publications; 2023. pp. 3–17.

31.

Kratz AL, Alschuler KN, Ehde DM, von Geldern G, Little R, Kulkarni S, et al. A randomized pragmatic trial of telephone-delivered cognitive behavioral-therapy, modafinil, and combination therapy of both for fatigue in multiple sclerosis: the design of the “COMBO-MS” trial. Contemp Clin Trials. 2019;84:105821. [DOI] [PubMed]

32.

Adlung L, Cohen Y, Mor U, Elinav E. Machine learning in clinical decision making. Med. 2021;2:642–65. [DOI] [PubMed]

33.

Li T, Wang Z, Lu W, Zhang Q, Li D. Electronic health records based reinforcement learning for treatment optimizing. Inf Syst. 2022;104:101878. [DOI]

34.

Nag N, Yang X, Jelinek G, Neate S, Simpson-Yap S. Undertaking specific stress-reducing activities are associated with reduced fatigue and depression, and increased mastery, in people with multiple sclerosis. Mult Scler Relat Disord. 2022;62:103804. [DOI] [PubMed]

35.

Bradson ML, Cadden MH, Guty ET, Riegler KE, Thomas GA, Graham-Engeland JE, et al. Coping style moderates the effect of pain on depression symptoms in multiple sclerosis. Arch Clin Neuropsychol. 2022;37:1515–26. [DOI] [PubMed]

36.

Montazeri S, Aghaei A, Golparvar M. Mindfulness-integrated cognitive behavioral therapy: Does it effective on stress coping strategies in women with multiple sclerosis? Caspian J Intern Med. 2022;13:634–8. [DOI] [PubMed] [PMC]

37.

Rodgers J, Friede T, Vonberg FW, Constantinescu CS, Coles A, Chataway J, et al. The impact of smoking cessation on multiple sclerosis disease progression. Brain. 2022;145:1368–78. [DOI] [PubMed] [PMC]

38.

Polick CS, Polick SR, Stoddard SA, Braley TJ, Slavich GM. The importance of assessing life stress exposure in multiple sclerosis: a case report. Mult Scler Relat Disord. 2021;54:103145. [DOI] [PubMed] [PMC]