New Study Links Stress and MS, but the Association May Not Be Causal

A new study is lending more credence to the theory that multiple sclerosis (MS) may be linked in some way to stress, although the authors caution that it is exceedingly difficult to tease out whether the link is merely an association or whether stress might play a causal role.

The latest findings on the MS-stress connection were published in the European Journal of Neurology. Investigators from Sweden’s Karolinska Institute used data from questionnaires given to 2,930 people with MS and 6,170 controls to see whether any patterns could be found in terms of the occurrence of major life events and the onset of MS. The questionnaires focused on lifestyle environmental factors and, in particular, on 10 specific life events, such as loss of a loved one, unemployment, or the breakup of a marriage or long-term relationship. If a survey respondent said they had experienced one of those events, they were asked to indicate when it happened and how important the event was when it occurred. The investigators only included events in their analysis if the event happened prior to the onset of MS symptoms. Controls were matched to patients with MS based on age, sex, and residential area.

The results showed a statistically significant correlation. Patients who had undergone one of the key life events had an increased risk of MS ranging from 17% to 30%. The authors found the link between stressful life events and MS was higher for women in many cases and that the stressful event typically happened within 5 years prior to the onset of MS symptoms.

Xia Jiang, Ph.D., the corresponding author and colleagues, noted that the subject of MS and a possible link to stress has been studied quite a lot, although many of the studies have been small and had design flaws, which, among other things, have led to selection bias.

Furthermore, the results of the studies have been mixed; for example, the results of two major studies by Danish researchers that were published in 2014 showed that, on the one hand, children whose parents got divorced had a higher risk of MS as adults while on the other, adults who who had gone through a divorce or other stressful events did not have a higher risk of MS.

Related: A Differing View: The 'Inside-Out' Explanation of How Multiple Sclerosis Occurs​

Jiang told Managed Healthcare Executive the topic of stress and MS is controversial partly because inferring causal relationships from the associations shown in observational studies is problematic.

“For example, in retrospective studies, recall bias is a problem,” she said. “MS patients (or anyone who unfortunately gets ill) would be more likely to seek a reason for their disease, so they may recall and report their life events or other relevant events to a greater extent than healthy individuals.”

Prospective studies are also present issues, she said, because the neurological changes in a patient might start years before symptoms of MS are identified, and those changes might lead to negative impacts on the patient’s lifestyle and stress level.

“Stress and MS are both brain-related, [so] it’s difficult to prove causality,” she said. “The two conditions might exacerbate each other, or there might be a reciprocal relationship.”

Indeed, though her study found a notable association between MS and stress, Jiang said it’s far too soon to draw conclusions about the nature of the apparent correlation or what implications such a link might have for patient care.

What they can say, however, is that there seems to be enough evidence to warrant additional study.