Stressful life-events in childhood and risk of multiple sclerosis: a Danish nationwide cohort study

Background:Current knowledge concerning the association between exposure to stressful life-events (SFLEs) in childhood and later risk of multiple sclerosis (MS) is sparse.Objectives:We studied the associations between SFLEs in childhood and subsequent risk of MS in a nationwide cohort of 2.9 million Danes born from 1968 to 2011.Methods:A SFLE in childhood was defined as exposure before age 18 years to parental divorce, parental death, or death of a sibling, using information from the Danish Civil Registration System. MS cases in the cohort were identified in the Danish Multiple Sclerosis Registry. Associations of SFLE with MS risk were evaluated by incidence rate ratios (RR) of MS obtained in log-linear Poisson regression models.Results:Persons exposed to any SFLE in childhood were at 11% elevated risk of MS (RR = 1.11; 95% confidence interval: 1.03–1.20), compared to non-exposed persons. Stratification by subtype of SFLE showed that parental death and death of a sibling were not associated with MS risk. However, persons exposed to parental divorce were at 13% increased risk of developing MS compared to non-exposed (RR = 1.13; 1.04–1.23).Conclusions:Associations of SFLEs in childhood with risk of MS are weak. However, parental divorce is somehow associated with modestly increased risk of MS.

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Do positive or negative stressful events predict the development of new brain lesions in people with multiple sclerosis?

Psychological Medicine ◽

10.1017/s0033291713000755 ◽

2013 ◽

Vol 44 (2) ◽

pp. 349-359 ◽

Cited By ~ 28

Author(s):

M. N. Burns ◽

E. Nawacki ◽

M. J. Kwasny ◽

D. Pelletier ◽

D. C. Mohr

Keyword(s):

Multiple Sclerosis ◽

Depressive Symptoms ◽

Life Events ◽

Perceived Stress ◽

Stressful Life Events ◽

Brain Lesions ◽

Stressful Events ◽

Stressful Life ◽

Increased Risk ◽

Mri Scans

BackgroundStressful life events have long been suspected to contribute to multiple sclerosis (MS) disease activity. The few studies examining the relationship between stressful events and neuroimaging markers have been small and inconsistent. This study examined whether different types of stressful events and perceived stress could predict the development of brain lesions.MethodThis was a secondary analysis of 121 patients with MS followed for 48 weeks during a randomized controlled trial comparing stress management therapy for MS (SMT-MS) to a waitlist control (WLC). Patients underwent magnetic resonance imaging (MRI) scans every 8 weeks. Every month, patients completed an interview measure assessing stressful life events and self-report measures of perceived stress, anxiety and depressive symptoms, which were used to predict the presence of gadolinium-enhancing (Gd+) and T2 lesions on MRI scans 29–62 days later. Participants classified stressful events as positive or negative. Negative events were considered ‘major’ if they involved physical threat or threat to the patient's family structure, and ‘moderate’ otherwise.ResultsPositive stressful events predicted decreased risk for subsequent Gd+ lesions in the control group [odds ratio (OR) 0.53 for each additional positive stressful event, 95% confidence interval (CI) 0.30–0.91] and less risk for new or enlarging T2 lesions regardless of group assignment (OR 0.74, 95% CI 0.55–0.99). Across groups, major negative stressful events predicted Gd+ lesions (OR 1.77, 95% CI 1.18–2.64) and new or enlarging T2 lesions (OR 1.57, 95% CI 1.11–2.23) whereas moderate negative stressful events, perceived stress, anxiety and depressive symptoms did not.ConclusionsMajor negative stressful events predict increased risk for Gd+ and T2 lesions whereas positive stressful events predict decreased risk.

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Modifiable factors influencing relapses and disability in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458510367721 ◽

2010 ◽

Vol 16 (7) ◽

pp. 773-785 ◽

Cited By ~ 46

Author(s):

MB D'hooghe ◽

G. Nagels ◽

V. Bissay ◽

J. De Keyser

Keyword(s):

Multiple Sclerosis ◽

Vitamin D ◽

Life Events ◽

Strong Evidence ◽

Stressful Life Events ◽

Stressful Life ◽

Fertility Treatment ◽

Increased Risk ◽

Vitamin D Levels ◽

Modifiable Factors

A growing body of literature indicates that the natural course of multiple sclerosis can be influenced by a number of factors. Strong evidence suggests that relapses can be triggered by infections, the postpartum period and stressful life events. Vaccinations against influenza, hepatitis B and tetanus appear to be safe. Surgery, general and epidural anaesthesia, and physical trauma are not associated with an increased risk of relapses. Factors that have been associated with a reduced relapse rate are pregnancy, exclusive breastfeeding, sunlight exposure and higher vitamin D levels. A number of medications, including hormonal fertility treatment, seem to be able to trigger relapses. Factors that may worsen progression of disability include stressful life events, radiotherapy to the head, low levels of physical activity and low vitamin D levels. Strong evidence suggests that smoking promotes disease progression, both clinically and on brain magnetic resonance imaging. There is no evidence for an increased progression of disability following childbirth in women with multiple sclerosis. Moderate alcohol intake and exercise might have a neuroprotective effect, but this needs to be confirmed.

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Stressful Life Events Precede Exacerbations of Multiple Sclerosis

Psychosomatic Medicine ◽

10.1097/00006842-200211000-00009 ◽

2002 ◽

Vol 64 (6) ◽

pp. 916-920 ◽

Cited By ~ 2

Author(s):

Kurt D. Ackerman ◽

Rock Heyman ◽

Bruce S. Rabin ◽

Barbara P. Anderson ◽

Patricia R. Houck ◽

...

Keyword(s):

Multiple Sclerosis ◽

Life Events ◽

Stressful Life Events ◽

Stressful Life

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Relationship of cardiovascular reactivity, stressful life events, and multiple sclerosis disease activity

Brain Behavior and Immunity ◽

10.1016/s0889-1591(03)00047-3 ◽

2003 ◽

Vol 17 (3) ◽

pp. 141-151 ◽

Cited By ~ 32

Author(s):

Kurt D Ackerman ◽

Angela Stover ◽

Rock Heyman ◽

Barbara P Anderson ◽

Patricia R Houck ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Activity ◽

Life Events ◽

Cardiovascular Reactivity ◽

Stressful Life Events ◽

Stressful Life ◽

Multiple Sclerosis Disease ◽

Relationship Of

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A temporal framework for understanding the effects of stressful life events on inflammation in patients with multiple sclerosis

Brain Behavior and Immunity ◽

10.1016/j.bbi.2005.03.011 ◽

2006 ◽

Vol 20 (1) ◽

pp. 27-36 ◽

Cited By ~ 50

Author(s):

David C. Mohr ◽

Daniel Pelletier

Keyword(s):

Multiple Sclerosis ◽

Life Events ◽

Stressful Life Events ◽

Stressful Life

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Childhood sexual abuse, stressful life events and risk for major depression in women

Psychological Medicine ◽

10.1017/s003329170400265x ◽

2004 ◽

Vol 34 (8) ◽

pp. 1475-1482 ◽

Cited By ~ 256

Author(s):

KENNETH S. KENDLER ◽

JONATHAN W. KUHN ◽

CAROL A. PRESCOTT

Keyword(s):

Sexual Abuse ◽

Major Depression ◽

Childhood Sexual Abuse ◽

Life Events ◽

Stressful Life Events ◽

Population Based ◽

Stress Sensitivity ◽

Stressful Life ◽

Increased Risk

Background. In animals, early trauma can produce long-lasting changes in sensitivity to the pathogenic effects of stress. To explore whether similar processes occur in humans, we examine whether childhood sexual abuse (CSA) in women alters sensitivity in adulthood to the depressogenic effects of stressful life events (SLEs).Method. A history of CSA was obtained from a population-based sample of 1404 female adult twins. Cox Proportional hazard models were used to predict onsets of episodes of DSM-III-R major depression (MD) in the past year from previously assessed levels of neuroticism (N), CSA and past-year SLEs scored on long-term contextual threat.Results. In the best-fit model, onset of MD was predicted by CSA, SLEs and N. Individuals with CSA (and especially with severe CSA) had both an overall increased risk for MD and a substantially increased sensitivity to the depressogenic effects of SLEs. A ‘dose–response’ relationship between severity of CSA and sensitivity to SLEs was clearer in those with low to average levels of N than in those with high levels of N.Conclusion. As documented with physiological responses to a standardized laboratory stressor, CSA increases stress sensitivity in women in a more naturalistic setting. Both genetic and early environmental risk factors can produce long-term increase in the sensitivity of individuals to depressogenic life experiences.

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Association between stressful life events and exacerbation in multiple sclerosis: a meta-analysis

BMJ ◽

10.1136/bmj.38041.724421.55 ◽

2004 ◽

Vol 328 (7442) ◽

pp. 731 ◽

Cited By ~ 208

Author(s):

David C Mohr ◽

Stacey L Hart ◽

Laura Julian ◽

Darcy Cox ◽

Daniel Pelletier

Keyword(s):

Multiple Sclerosis ◽

Life Events ◽

Stressful Life Events ◽

Meta Analysis ◽

Weighted Average ◽

Stressful Life ◽

Average Effect ◽

Exclusion Criteria ◽

Immune Mediators ◽

Increase In Risk

AbstractObjective To quantify the association between stressful life events and exacerbations of multiple sclerosis.Data sources PubMed, PsychInfo, and Psychological Abstracts searched for empirical papers from 1965 to February 2003 with terms “stress”, “trauma”, and “multiple sclerosis”.Review methods Three investigators independently reviewed papers for inclusion/exclusion criteria and extracted the relevant data, including methods, sample statistics, and outcomes.Results Of 20 studies identified, 14 were included. The meta-analysis showed a significant increase in risk of exacerbation in multiple sclerosis after stressful life events, with a weighted average effect size of d = 0.53 (95% confidence interval 0.40 to 0.65), P < 0.0001. The studies were homogenous, q = 16.62, p = 0.22, i2 = 21.8%. Neither sampling nor study methods had any effect on study outcomes.Conclusions There is a consistent association between stressful life events and subsequent exacerbation in multiple sclerosis. However these data do not allow the linking of specific stressors to exacerbations nor should they be used to infer that patients are responsible for their exacerbations. Investigation of the psychological, neuroendocrine, and immune mediators of stressful life events on exacerbation may lead to new behavioural and pharmacological strategies targeting potential links between stress and exacerbation.

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Association of Stress with Risk of Dementia and Mild Cognitive Impairment: A Systematic Review and Meta-Analysis

Journal of Alzheimer s Disease ◽

10.3233/jad-210094 ◽

2021 ◽

pp. 1-18

Author(s):

Katherine H. Franks ◽

Lisa Bransby ◽

Michael M. Saling ◽

Matthew P. Pase

Keyword(s):

Systematic Review ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Life Events ◽

Perceived Stress ◽

Stressful Life Events ◽

Meta Analysis ◽

Stressful Life ◽

Total N ◽

Increased Risk

Background: Although many studies have investigated the association between stress and risk of dementia, findings are inconsistent due to the variation in the measures used to assess stress. Objective: We conducted a systematic review and meta-analysis to investigate the association between psychological stress (including neuroticism, stressful life events, and perceived stress) and the risk of incident dementia and mild cognitive impairment in adults. Methods: PsycINFO, Embase, and MEDLINE were searched to October 2020 for eligible observational, prospective studies. Of the 1,607 studies screened, 26 (24 unique cohorts) were included in the qualitative analysis and 16 (15 unique cohorts) were included in the quantitative analysis. Results: Across studies, higher perceived stress was significantly associated with an increased risk of mild cognitive impairment (Cases/Total N = 207/860: hazard ratio [HR] = 1.19, 95% confidence interval [CI] = 1.03–1.38) and all-cause dementia (Cases/Total N = 203/1,882: HR = 1.44, 95% CI = 1.07–1.95). Exposure to two or more stressful life events (versus none) was significantly associated with an increased risk of all-cause dementia (Cases/Total N = 3,354/11,597: HR = 1.72, 95% CI = 1.14–2.60), while one or more stressful life events was not. Higher neuroticism was significantly associated with an increased risk of Alzheimer’s disease dementia (Cases/Total N = 497/4,771: HR = 1.07, 95% CI = 1.01–1.12), but not all-cause dementia. Conclusion: This review suggests that psychological stress in adulthood is associated with an increased risk of dementia. Further research is needed to clarify the mechanisms underlying these associations.

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