Psychological Stress Linked with Autoimmune Disease

Psychological Stress Linked with Autoimmune Disease


Ah Sweden, land of the midnight sun, delicious
cherry-flavored fish, and a national medical registry that captures every single living
person in the country. Leveraging Sweden’s robust patient registry
is something of a right of passage for epidemiologists looking for population-level evidence of disease
association, and this paper, appearing in the Journal of the American Medical Association,
found one that seems to be fairly compelling. The study asked the question of whether psychiatric
stress-related disorders like post-traumatic stress disorder are linked to autoimmune diseases
(like Lupus and Hashimoto’s thyroiditis – actually a total of 41 autoimmune diseases. That’s the power of big data). Overall, the authors identified 106,464 Swedes
who had suffered from a stress-related disorder and age- and sex-matched them to 1,064,640
Swedes who had not. They then looked to see, over a period of
almost 30 years, how many would develop autoimmune diseases. The results look like this:
There’s a slightly higher rate of autoimmune disease in those who had a prior stress disorder. Take my word for it, it’s a slightly bigger
piece of pie. How much bigger? Well, if you took 1000 people with stress
disorders, 9 would develop an autoimmune condition over the next year, compared to 6 out of 1000
of those without stress disorders. This modest increased risk persisted even
after accounting for differences in marital status, comorbidities, history of psychiatric
disorders, and educational level. Why? Well, the authors argue that these stressful
episodes might lead to alterations in the immune system via a variety of mechanisms
(none were directly studied in this study) such as cortisol depression or upregulation
of inflammatory cytokines. You and I might argue that unmeasured factors
like alcohol intake and smoking might be equally important here, either as mediators of the
observed link (maybe people who experience a significant
stress start drinking more which may lead to autoimmunity) or as a confounder
(maybe people who smoke are more likely to have stress reactions and more likely to have
autoimmunity and the two factors aren’t linked at all). The authors note that given the small absolute
risk of autoimmunity, we shouldn’t be screening patients with stress-disorders for autoimmune
disease. But the study did observe at least one interesting
effect that needs further exploration. Those patients who used SSRIs for stress disorders
in this study had a substantially higher rate of autoimmune disease, but the LONGER they
used SSRIs, the lower the risk became. I asked lead author Dr. Huan Song about this
paradoxical finding. She told me she suspects that SSRIs are a
marker for severity of the stress-disorder, leading to the higher effect size, but that
the persistent use of SSRIs could be beneficial. Perhaps they modify some of the effects of
stress. This means there’s a potential therapeutic
target here. When will we know for sure whether this link
represents real physiology and not statistical artifact? Don’t stress – those studies are ongoing.

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