A new study has strengthened the suggestion that depression is a risk factor for developing seronegative rheumatoid arthritis.
Depression is already known to be associated with increased systemic inflammation and autoimmune conditions such as lupus, psoriasis and inflammatory bowel disease.
So a team led by Dr Jeffrey Sparks, a rheumatologist at Brigham and Women’s Hospital and assistant professor of medicine at Harvard, hypothesised that it might also be involved in the pathogenesis of RA.
They performed a prospective cohort study using pooled data from the Nurses Health Study and Nurses Health Study II, a total of almost 200,000 women, a quarter of whom had depression. The study abstract was presented at the American College of Rheumatology annual meeting in Atlanta in November.
To minimise reverse causation bias – the possibility that early undiagnosed symptoms were causing depression – the study imposed a long time lag of at least four years between the onset of depression and diagnosis of RA before a case would be counted.
When the data was age-adjusted, women with depression had a 41% higher incidence of all RA. This came down to 28% when also adjusted for income, smoking, BMI and other potential confounders.
For seronegative RA only, however, the risk was 70% higher when adjusted for the full list of covariates.
For seropositive RA, the increase did not reach statistical significance.
Speaking after the conference, Dr Sparks said while a few studies had looked for an association, none had clearly demonstrated that the arthritis came after the depression.
“Certainly there’s a notion that mental health affects your immune system and affects levels of systemic inflammation, so you can certainly make a story that outside stressors can contribute to pathogenesis of inflammatory diseases,” he told <em>Rheumatology Republic</em>.
“Obviously a disorder like RA that has so many quality-of-life features is particularly difficult to study: you’re in pain, you don’t sleep well, you’re gaining weight, you’re not as active –you can see how any of these things are going to affect your mental health.
“So there’s a chicken-and-egg argument: are you depressed because you’re in pain, are you in pain because you’re depressed?
“That’s why constructing the timeline of when these things occur is really important. We had at least a four-year buffer between when the depression was assessed and when RA was diagnosed.”
If anything, he said, the time interval was conservative and cases may have been missed.
Dr Sparks said the finding was exciting because there weren’t many known risk factors for the seronegative form of the disease, which comprises about a third of cases.
It was less well understood because it was less common and more heterogeneous, with different disease domains, and it might actually turn out to be a collection of entities rather than one.
“I think this opens up a path for a pretty large patient population to try to understand why they go on to develop it,” Dr Sparks said.
“It does open the avenue to explore other mental health and traumatic factors – PTSD, anxiety, childhood abuse, sexual abuse – maybe those are the ones that put people on the path to seronegative RA.”