MS patients frequently report elevated levels of stress prior to initial diagnosis and/or disease exacerbation (Warren et al., 1982; Grant et al., 1989; Ackerman et al., 2000; Mohr et al., 2000; Mohr et al., 2004). A recent metaanalysis was conducted on 14 studies investigating the impact of stressful life events on MS exacerbation. The results indicated that stressful life events significantly increased the risk of subsequent disease exacerbation (Mohr et al., 2004). Importantly, 13 of the 14 studies measured common stressful life events, mostly interpersonal stressors at family and work. However, one of the 14 studies did not observe a negative effect of stress on MS. This study examined the impact of a traumatic stressor, missile attacks during the Gulf War, finding reduced relapse rates and no change in lesion development (Nisipeanu and Korczyn, 1993). Thus, the characteristics of the stressor may alter the impact of stress on initial susceptibility and disease course in MS. Chronic social stressors appear to exacerbate disease, whereas acute traumatic stressors may have a beneficial effect.
The majority of studies examining the relationship between stress and MS have used patient self-reports of symptoms and/or neurologist ratings of symptoms that are based in part on patient reports. Therefore, it is possible that reports of disease exacerbations during periods of stress may be biased by the patient's mood or some other spurious subjective variable. Objective markers of disease exacerbation are clearly needed to resolve this issue, however only one human study meets this criterion. Using a prospective design, Mohr and colleagues (2000) examined the association between stressful life events and subsequent lesion development in MS patients. To objectively measure changes in blood-brain barrier (BBB)
disruption that are linked to CNS inflammation in MS, patients received a monthly gadolinium (Gd+) MRI. Gd+ is injected peripherally and then crosses the BBB at sites of MS inflammation, allowing the quantification of active lesions during the MRI scan. Patient reports of stressful life events were found to predict the development of new Gd+ brain lesions. Importantly, chronic social stressors and disruptions in daily routine were found to have the strongest relationship with lesion development.
Although human studies suggest that social stress is correlated with later MS disease exacerbation, animal studies are critical to determine whether there is a causal relationship between stress and disease exacerbation. Animal experiments are advantageous because the stressor can be experimentally manipulated and its impact on disease course can be quantified using objective behavioral and physiological markers of disease. Animal studies are also important because they can readily identify the underlying immune and endocrine mechanisms mediating the effects of social stress on disease.
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