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By Darcy Rhyno

 

One morning about 16 years ago, Derek Stewart woke up in his Halifax home with a sore arm. He thought it was because he had been sleeping with his arm at an odd angle. But the pain just didn’t go away. “In about 30 days, I was pretty much incapacitated,” says Stewart. “I had pain from the top of my head to the tip of my toes.” He was 35 years old. The second of his four children had just been born.

“I went to see my family doctor. She poked and prodded,” Stewart says, describing his efforts to get to the bottom of the pain. At first his doctor was reluctant to diagnose a disease—he was young and otherwise in good health. Stewart continued to struggle. “It was that much of an effort just to make the body move. To go from the bedroom downstairs to the living room, by the time I got there I was exhausted. My wife used to help me put on my socks. It wasn’t getting any better, so I started taking handfuls of Tylenol all day just to move.”

By the time he returned to his doctor, he couldn’t open his hands, it was so painful. “She sent me for bloodwork,” says Stewart. “Lo and behold, I had rheumatoid arthritis.” Like about 300,000 other Canadians, he has been living with the disease ever since. As the father of young children, rheumatoid arthritis (RA) quickly took a toll on Stewart’s family life. “It was so bad, I was dropping everything. I wouldn’t hold the kids because I was scared I was going to drop them, too. Not being able to hold your kids, that’s a weight on your shoulders.”            

Even while carrying around such a heavy load of parental frustration and guilt, Stewart often found himself physically unable to interact with his children. “When I had to move, I knew it was going to hurt a lot.” Increasingly, he withdrew from family life. “All I wanted to do was find a comfortable place and not move.” Stewart knew that the worst thing he could do for his arthritis was to stop moving, but he just couldn’t get himself up and about.

Along with his family life, his mental state deteriorated. “I was experiencing feelings of hopelessness,” says Stewart. “I didn’t even want to get out of bed in the morning.” He wasn’t sure anymore if RA was the only disease he was suffering from. “I had more sinister thoughts, especially when my pain was really bad.” Although he was never diagnosed with depression, he now believes all these years later, “that it was probably depression.”

 

RA and depression:

the autoimmune link

“We’ve long known there are higher rates of depression in people who have RA,” says Dr. Trudy Taylor, a rheumatologist at the Nova Scotia Rehabilitation Centre and Arthritis Centre, part of the Queen Elizabeth II Health Sciences Centre in Halifax.

Much of the scientific literature, like a 2017 Danish study, agrees. “An epidemiological link between psychiatric and autoimmune disorders has been observed for almost a century…The two classes of disorders overlap in the same individuals at a higher frequency than chance.” The study is entitled A Bidirectional Relationship Between Depression and the Autoimmune Disorders—New perspectives from the National Child Development Study by Jack Euesden, Andrea Danese, Cathryn M. Lewis and Barbara Maughan.

According to the Arthritis Society website, “RA is an autoimmune disease where the body’s immune system—which normally functions to protect us against infections—mistakenly attacks the lining of the joints. The cause of this malfunctioning immune system is still unknown.” RA is just one of what could be more than 100 autoimmune diseases.

Derek Stewart knows all about this category of diseases. “Unfortunately, I developed a couple of other autoimmune issues,” he says. “I’ve got a low thyroid, I’ve got vitiligo—my pigment cells are self-destructing—I have celiac disease, and I’m lactose intolerant. So, I’ve got a little autoimmune storm going on—five strikes against me.” 

Mental illnesses like depression may also be associated with autoimmune diseases like RA. It’s not surprising that the physical pain caused by RA can lead to serious life consequences such as those that Stewart experienced—loss of income and work—and to depression. As Dr. Taylor puts it, “For a long time, we thought that people with RA have depression because they are in pain and can’t function the way they want to, and perhaps aren’t sleeping as well. People who have RA and an associated depression don’t do as well. They have poorer response to medication and poorer functional status. Their quality of life tends to be lower.”

If the physical symptoms of RA lead to depression, so the theory goes, then the symptoms of depression would then worsen the pain and other symptoms of RA. As the Danish study puts it, “In rheumatoid arthritis, low mood may predict subsequent worsening of symptoms in autoimmune disorder patients.” In Derek Stewart’s case, he found himself feeling so low at times that he didn’t want to get out of bed. Doing so led to inactivity and weight gain, both of which aggravated his RA symptoms. In this way, it seems logical that the patient spirals ever downward, the two diseases aggravating each other, leading to increasingly challenging symptoms.

 

Inflammation: the physical link

That common-sense way of thinking about RA as a risk factor for depression (pain and other physical symptoms lead to low mood) does not accurately reflect either the true nature of depression as a disease or the deeper way these diseases are linked. Science has uncovered another layer in the relationship between the two diseases. A hint to that deeper link comes in the very etymology of the word “arthritis” or swelling of the joints, which comes from the roots “arthro” meaning joint and “itis” meaning “inflammation.”

As Dr. Taylor puts it, when it comes to the possible causes of both diseases, “there’s even more to it than that. It turns out inflammation probably plays a role.” That role is complex and still being explored by scientists. “There’s still a lot more to learn,” says Dr. Taylor, “however it does appear that the proteins that drive inflammation in the body also have an effect on the brain to cause or worsen depression.”

One piece of evidence researchers and health professionals cite to support their theory that depression is linked to inflammation is recent research into the somewhat surprising side effects of some drugs. According to the Danish study, “anti-inflammatory medications appear to have antidepressant effects.”

Dr. Taylor suggests we need to think about both RA and depression as physical diseases. “Our brains are affected by what’s going on in our bodies the same way that our muscles and joints are. When we think of autoimmune diseases, your immune system is ubiquitous—it’s everywhere in your body, so it can affect any organ in your body, including your brain.” She says the theory that a mental illness could be caused by the same physical mechanisms that cause swelling of the joints in RA is counter-intuitive, and was therefore, as she puts it, “a very novel idea.”

If inflammation is at the root of both, then it’s possible that depression is a risk factor for RA and other autoimmune diseases, as well as the other way around. The Arthritis Society lists a number of risk factors for RA – genetics, gender (women are two to three times more likely to develop RA), hormones, age (RA commonly develops between 40 and 60 years of age) and environmental factors, the most common of which is smoking. Depression is not on that list.

 

New research

However, two new pieces of research are shedding more light on the complex relationship between these diseases. Both are recent large-scale population studies. One is a 2016 Taiwan study called “Bidirectional Associations Between Rheumatoid Arthritis and Depression: A Nationwide Longitudinal Study.” It concludes that, while the mechanisms are not fully understood, “Our findings suggest that RA increases the risk of subsequent depression, and the onset of depression also increases the risk of developing RA.”

The other is the 2017 Danish study cited earlier. In it, the researchers conclude that they have found a significant two-way link between major depressive disorders and the autoimmune disorders. The researchers point out that their findings support previous studies, which conclude that the inflammation that causes autoimmune disorders such as RA is also linked with depression.

“Our results point to a bidirectional relationship between depression and the autoimmune disorders,” concludes the Danish study. “This suggests that shared risk factors may contribute to this relationship, including both common environmental exposures that increase baseline inflammation levels, and shared genetic factors.” The Danish study goes further, suggesting more work needs to be done in identifying some of the mechanisms that link the two diseases, “perhaps via some depression-associated behaviour such as diet, or an environmental risk factor shared between the two phenotypes, such as cigarette smoking.”

 

Why it matters

“My big caution when I think about this is,” says Dr. Taylor, “we’re just hitting the tip of the iceberg. This is complex. We don’t know that all of these things are related to inflammation itself, and just treating inflammation will make them go away. There’s a lot more that we have to learn.”

Her opinion as a practising rheumatologist who sees patients almost every day with both diseases is confirmed by the Danish researchers. “The possible mechanisms linking psychiatric disorders and RA still remain unclear.” The Taiwanese researchers concur. “Although the current study provided support for an empirical link between RA and depression, the exact pathophysiological mechanisms involved in these two illnesses still remains elusive.”

At the same time, these recent findings about the bi-directional relationship between RA and depression holds great promise for patients. “We’ve gotten much better at treating the joints,” says Dr. Taylor. “This may open up the door on whole new ways we can help manage the symptoms and signs of this disease, and improve quality of life and function for patients who have RA.”

Furthermore, if researchers can discover which of these diseases leads to the other—if that’s even the case—we can learn more about the causes of both. According to the Danish study, “Investigating the relationship between depression and autoimmune disorders, and identifying the factors driving it, will inform theories that the aetiology of depression involves immune processes.” Figuring out what causes clinical depression will likely lead to improved treatment.

Patients may already be seeing some benefits. Dr. Taylor says as we learn more, the science will inform how these diseases can best be managed. For example, medications are costing patients dearly. “Notably,” reports the Danish study, “those RA patients suffering from concomitant depression had nearly a 7.2 per cent increase in medical costs per year… and more than double the likelihood of mortality compared to patients with RA only, suggesting that prompt provision of psychosocial support is of utmost importance.”

Medications helped Stewart get the pain and other symptoms of RA, along with his other autoimmune ailments and possible depression under control, but he used non-medical methods as well such as running, tai chi and a kind of mental muscle building. “It’s probably what they refer to now as mindfulness, just waging the ongoing battle in your head. The brain and the body have this little discussion. Sometimes the body wins, sometimes the brain wins. You just work through it.”

Another immediate impact is simply the patient’s perception of the disease. If the patient understands that the symptoms of mental illness and of rheumatoid arthritis could share root causes, that knowledge itself is another piece of the management puzzle. “There’s a positive when people feel validated in how they feel,” says Dr. Taylor.

When Derek Stewart was first diagnosed with RA and symptoms of depression began to appear, concern for his family set him back even further. Years later, it was this same concern that helped lead him back to better times.

“We had two kids at that time. Both my wife and I were working,” says Stewart. “I couldn’t afford to sit in bed. Some days you just feel so horrible physically, and in your head, but you have to convince yourself to do stuff when the kids want to play.” His youngest child is now 11 years old. She still likes stuffed animals, but, says Stewart, the teen years are just around the corner, so he just works through it. “Those days are going to be gone. You never get them back.”  

 

 

Header credit: Bigstock/Sergey Furtaev

Header no caption

 

Intro credit: Courtesy of Derek Stewart

Caption: When he was 35 Derek Stewart was diagnosed with  rheumatoid arthritis.

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