In 2006, Crystal Jackson was a single mother living in Maryland, working as a bartender, when she took a nasty fall at work and fell headlong into a cycle of pain and emotional distress.
As a result of her injuries, she was forced to apply for workers’ compensation and disability insurance. A few years later, she noticed a rash on her fingernails, which was diagnosed as psoriasis. Then, about a year and a half ago, pain spread to her fingers and toes, and just as she was experiencing stress over paying doctors’ bills, she was diagnosed with psoriatic arthritis.
“It’s not easy going through the process and dealing with all of that,” she says. “It’s a lot of anxiety, a lot of depression.”
Stress is a common trigger for psoriatic disease, and many patients, like Jackson, have experienced the one-two punch of stress and psoriatic disease. Living with the disease can result in more stress, which, in turn, can lead to a new flare. Those living with psoriatic disease can find themselves in what feels like a never-ending cycle.
An August 2010 study published in the journal Archives of Dermatology found that those living with psoriasis have a 39 percent increased risk of being diagnosed with depression than those without the disease, while the risk of an anxiety diagnosis is 31 percent higher. Another study, published in the Journal of Rheumatology in April 2014, found that those with psoriatic arthritis and psoriasis suffer higher rates of anxiety and depression than those with psoriasis alone.
And depression may actually increase the risk of developing psoriatic disease. A study published in the Journal of the European Academy of Dermatology and Venereology in September 2013 found that in severely depressed women in the United States, the risk of developing psoriasis may be nearly double that of those who are not depressed.
Growing evidence indicates that the same processes that trigger inflammation in psoriatic disease may also create changes in the brain that affect emotional states. Scientists are now learning more about the correlation among stress, depression and psoriatic disease and are testing new therapies that could treat all of those things.
In light of this evidence, Jackson’s experience isn’t surprising. About a year ago, she started treatment for depression and anxiety, taking Zoloft (sertraline), an antidepressant, and trazodone, an anti-anxiety drug. To her surprise, her psoriasis cleared almost completely, even on her nails. Her joint symptoms improved, as well.
The biology of depression
Researchers began making the connection between the immune system and depression while doing cancer research. Like those living with psoriatic disease, cancer patients sometimes suffer depression, but for some, it isn’t the illness that causes depression, it’s the treatment. The culprit is cytokines, the molecules employed in some cancer treatments. These inflammatory proteins boost the depleted immune system in cancer patients, but doctors have noted that a significant numbers of cancer patients become depressed and anxious following treatment that contains the same cytokines involved in psoriatic disease.
Even in those who are not undergoing these treatments — or who may not have cytokine-driven diseases like psoriasis — depression and cytokines seem to go hand in hand. In a January 2006 paper published in Trends in Immunology called “Cytokines Sing the Blues: Inflammation and the Pathogenesis of Depression,” researchers noted increased levels of cytokines, including tumor necrosis factor-alpha (TNF-alpha) — a key player in psoriatic disease — in people with depression.
Understanding how cytokines are released in the body offers more clues about how they can affect both inflammation and depression. Theoharis Theoharides, M.D., a researcher at Tufts University, says it starts with mast cells, one of several sources of cytokines that can drive psoriasis. Stress, in the form of peptides such as corticotropin-releasing hormone (CRH) and the nefarious-sounding substance P, can trigger mast cells to release cytokines and start the inflammatory process, says Theoharides.
Stress triggers the release of CRH and substance P — both of which are found in psoriasis plaques and stimulate mast cells to release TNF-alpha — into the brain and skin. CRH has also been found in the joints of people with inflammatory arthritis, such as psoriatic arthritis. Stress signals travel from the central nervous system, housed in the brain and spinal cord, to the peripheral nervous system, which includes nerves in the skin, says Caitriona Ryan, a dermatologist at Texas A&M Health Science Center.
“It’s like a tree,” Ryan says. “From the central nervous system, it sends messages through twigs out to the peripheral nervous system.”
This sets the immune response in motion, leading to the release of TNF-alpha and other cytokines throughout the body. Take, for example, interferon, one of the cytokines used in cancer treatments. When Jonathan Cavanagh, M.D., a psychiatrist at the University of Glasgow, realized that certain interferon treatments could result in depression, he began investigating what happens to the brain when the body experiences inflammation. He studied the brains of mice engineered for a disease similar to psoriasis and found increased levels of interferon that lasted for a long period of time. The results of the study were published in the April 2014 issue of Journal of Neuroinflammation.
Treating the skin, joints and mind
Cavanagh’s team found that the brains of the engineered mice also showed increased levels of other cytokines, including TNF-alpha. Previous research has shown that TNF-alpha may reduce levels of serotonin, a condition that has been associated with depression.
Armed with the knowledge that cytokines may be doing double duty in some psoriatic disease patients, leading to both physical and emotional disorders, doctors are developing new treatments that can stop the cycle of inflammation, stress and depression. But there are also older treatments. Because some drugs used to treat psoriatic disease, such as Enbrel (etanercept) and Humira (adalimumab), block TNF-alpha, these drugs might also block TNF-alpha’s disruption of serotonin in the brain.
Cavanagh conducted a small pilot study testing this theory in patients taking Humira for rheumatoid arthritis, and the hypothesis was borne out. The results appeared in an April 2010 article titled “Tumour Necrosis Factor Blockade Mediates Altered Serotonin Transporter Availability in Rheumatoid Arthritis: A Clinical, Proof of Concept Study” in the journal Annals of the Rheumatic Diseases.
The team found that blocking TNF-alpha prevented the serotonin depletion seen in depression, and patients experienced improvements in their mood and mental function. Cavanagh’s team is currently studying the effect of TNF-alpha blockers on depression in psoriasis patients and expects to share results soon.
Some patients may already be experiencing the emotional benefits of TNF-alpha blockers. Chris Griffiths, M.D., a dermatologist at the University of Manchester, has seen the psychological state of patients improve as quickly as one month after starting biologic therapy, sometimes before their skin clears up.
“Their psoriasis has not improved a whole lot at that stage, but the patients are different,” he says. “They say, ‘I feel marvelous. I feel really great.’”
A study of Enbrel published in The Lancet in January 2006 backs these observations. After three months of treatment, patients taking Enbrel experienced more improvement in their depression compared with patients taking a placebo. As researchers reported, improvements in mood didn’t always correspond to improvements in psoriatic disease.
The common trigger: stress
Some doctors are incorporating anti-anxiety drugs into psoriatic disease treatment, something Theoharides recommends particularly for patients whose disease is triggered by stress. Reducing anxiety could help reduce the release of stress chemicals such as CRH, potentially putting an early stop to the inflammatory reaction in the body, he says.
This approach worked for Jackson, the Maryland bartender injured in a fall. Shortly after starting Zoloft and trazodone, and adding methotrexate, a systemic treatment for psoriatic disease, her psoriasis and psoriatic arthritis greatly improved. In the past few months, however, her psoriatic disease has worsened, and she hopes to start a TNF-alpha blocker soon to see if that helps.
Adding a new drug into the mix may not be the only option, however. Some studies indicate that behavioral therapy may also be an effective treatment for psoriatic disease. In the 1990s, researchers from the University of Massachusetts published the results of a study looking at the effects of combining mindfulness therapy with phototherapy to treat psoriasis. The study appeared in the journal Psychosomatic Medicine in September 1998, in an article titled “Influence of a Mindfulness Meditation-Based Stress Reduction Intervention on Rates of Skin Clearing in Patients with Moderate to Severe Psoriasis Undergoing Phototherapy (UVB) and Photochemotherapy (PUVA).”
In the study, about half of the patients did a mindfulness meditation along with phototherapy. The other half received phototherapy alone. Researchers found that the group doing mindfulness therapy achieved clearer skin more quickly than the other group, suggesting that psychological treatment could be useful in treating psoriasis.
More recent research supports this idea. Griffiths practices a biopsychosocial model of treating psoriasis, taking a holistic approach to working with patients. He and his colleagues developed a cognitive behavioral therapy program designed to treat the psychological and physical symptoms of psoriasis together.
In a trial, patients were divided into two groups. All stayed on their psoriasis treatment, and one group also underwent six weeks of group therapy, where they learned coping skills and strategies for overcoming negative beliefs, Griffiths says. According to the results, published in the British Journal of Dermatology in March 2002, after six months, 64 percent of patients participating in group therapy achieved more than 75 percent improvement in their psoriasis, compared to only 23 percent of patients not in the therapy group.
Taking steps to improve emotional health can bring lasting benefits to patients’ overall well-being, says John Koo, M.D., a dermatologist at the University of California, San Francisco and a member of the National Psoriasis Foundation Medical Board who is also a trained psychiatrist. He encourages patients to explore ways of coping with the inevitable stresses of life, whether that is through meditation, exercise or listening to music.
Because their doctors may not be trained in psychiatry, or have the opportunity to address emotional issues during office visits, Koo says patients should take the lead to address emotional difficulties they may be experiencing.
Jackson, too, urges patients to speak up and be open with their doctors about what they’re feeling.
“Don’t deny your symptoms,” she says. As soon as she began noticing her mood swings, Jackson asked her doctor about it and soon started psychiatric treatment.
“You have to try to keep yourself healthy,” Jackson says. “And the only way to do that is letting your doctors know what you’re going through.”
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