Keep Depression, Anxiety Screening Top of Mind in Patients With Psoriatic Disease

Pat Kelly

July 17, 2023

DUBLIN, Ireland — Patients with psoriatic disease (PsD) face an elevated risk for depression and suicidality that stems from both pathologic inflammatory factors associated with the disease as well as societal stigma, warranting routine screening and having community contacts for mental health professional referrals, Elizabeth Wallace, MD, said at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

Wallace, of Cherry Hills Dermatology, Englewood, Colorado, discussed the complex interactions between mental illness and psoriatic disease and the potential pitfalls of this comorbidity for these patients. The topic of mental health is "consistently at the top of our patients' minds, and certainly our minds too," said session co-moderator and GRAPPA president-elect Joseph Merola, MD, MMSc.

"In the US, around 17% of people with psoriasis have depression vs 9% in those without psoriasis," Wallace explained. "Psoriasis patients are twice as likely to have depression, compared to those without psoriasis, and psoriasis patients are 33% more likely to attempt suicide and 20% more likely to complete suicide, compared to those without psoriasis." More severe psoriasis and younger age of onset are also associated with a greater likelihood of suicidality, she added.

Mediators of Depression

"The inflammatory mechanisms driving PsD can drive depression and anxiety, and vice-versa," she said. "There are often also genetic links, for example genetic variations in serotonin receptors, and psychological issues in psoriatic disease are predictably worsened by feelings of stigmatization, embarrassment, and social isolation."

There are also efforts underway in clinics to "normalize" screening for anxiety and depression among this patient cohort, Wallace said. "We know that our psoriasis patients face social stigma from the visibility of their disease, and that stress can lead to flares of their condition," she told the attendees. "We also know that patients who experience stigma also have an increased risk of depressive symptoms. We all know now that psoriasis has well-established pathways with upregulated proinflammatory cytokines.

"Increased cytokines stimulate indoleamine 2,3-dioxygenase, which converts tryptophan to kynurenine. Kynurenine is metabolized to quinolinic acid, which is neurotoxic." She explained that because serotonin derives from tryptophan, decreases in tryptophan lead to reduced serotonin, and therefore increased risk of depression.

Interleukin-6 is known to be upregulated in depression and downregulated with the use of antidepressant medications, Wallace said. Mouse models in research have shown that deletion of the IL-6 gene produces antidepressant effects, and studies in humans have shown that IL-6, more than any other serum cytokine, is found at higher levels in humans with depression and psoriatic disease. 

IL-17 is also implicated in psoriatic disease and mental health problems, Wallace said. "With stress, you get upregulation of the Tc17 cells, which produce IL-17," she explained. "IL-17, along with other inflammatory markers, can actually make the blood–brain barrier more permeable, and when you get more permeability to the blood–brain barrier, you get these cytokines that can cross from the periphery and into the brain. 

"With this crossing into the brain, you get further activation of more Th17 [cells] and that, on neurons, leads to increased potassium production, which is directly neurotoxic, so you get neuron destruction."

Talking About Depression

"So, what can we share with our patients?" Wallace asked. "We can discuss with them that psoriatic patients in general are more likely to be depressed or to have higher rates of suicide. The literature consistently shows that patients whose psoriasis is successfully treated experience reduced depression, and we can provide an understandable review of systemic medications, with warnings on depression and/or suicidality."

Wallace advised to screen for depression with the Patient Health Questionnaire-2 (PHQ-2), a validated, two-item tool that asks, 'Over the past 2 weeks, how often have you been bothered by having little interest or pleasure in doing things?' and 'Over the past 2 weeks, how often have you been bothered by feeling down, depressed, or hopeless?'

She presented a case study illustrative of the type of presentation she sees in her clinic. It involved a 32-year-old man with plaque psoriasis and a high degree of body surface affected. "It's now July in Colorado, it's getting warm, people want to wear their shorts and T-shirts, but he said he could no longer hide his psoriasis," said Wallace. "Further, it's in areas that he cannot hide, such as his scalp, his beard, and he also has nail disease. Often, these patients don't want to shake hands with their bosses or their colleagues and that's very embarrassing for them." 

Wallace explained that this patient had seen advertisements for biologic drugs and requested to commence a treatment course. "During the exam, and now that you are developing some rapport with him, you discover that he is feeling down, is embarrassed at work and has started to avoid social situations." This is illustrative of a patient who should be screened for mental health conditions, specifically using PHQ-2, she said.   

"You can be the person at the front line to screen these patients for mental health conditions, and, specifically for depression, with PHQ-2," she said. PHQ-2 scores range from 0 to 6, and a score of 3 or higher is considered a positive screen.

"This is where your relationship with another health provider who is most qualified to care for these patients and validate them for their mental health condition can be absolutely critical," Wallace said. 

Successful PsD treatment lessens the risk for mental health comorbidities, and this is also seen in psoriatic arthritis, Wallace pointed out. Patient education is critical regarding their increased risk for depression and potential suicidal ideation, she added. 

"It's our job as clinicians to provide patients with an understandable, easy-to-digest review of systemic medications and warnings on depression and suicidality so that they can be aware of these factors."

Perspective From Dr Merola

Speaking with Medscape Medical News, Merola, a double board-certified dermatologist and rheumatologist at Brigham and Women's Hospital, Boston, discussed the interactions between mental and physical illness.

"One of the things we are learning is that it's very much a multifactorial issue, in that skin and joints contribute, in some obvious ways, to anxiety and depression, like the fact that somebody doesn't feel good about their appearance, or they can't complete daily activities," he said. "Those are the more obvious ones. But there is data and evidence that there is a biology behind that as well — inflammatory cytokines that drive skin disease probably also have a direct impact on the CNS and probably also drive anxiety and depression. 

"We know that disordered sleep contributes to anxiety — think about how we feel if we get a horrible night's sleep… it's hard to pick apart: 'Am I depressed, am I anxious because I am having too much coffee? Because I am fatigued?' So, we get into these circles, but the point is, we have to break these cycles, and we have to do it in multiple places. Yes, we have to fix the skin and the joints, but we also have to have interventions and think about how to screen for anxiety and depression. We also have to think about identifying disordered sleep, and how we intervene there as well."

These challenges require a collaborative approach among physicians. "We can help patients to build their team that gets them help for their skin, for their joints, for their anxiety or depression, their disordered sleep, for their nutritional disorders, their obesity, and so on. So, we are trying to pick apart and unpack those complexities," he said.

In regard to the potential impacts of this holistic strategy on physician workloads, Merola acknowledged it is important to consider physician wellness. "There's no question that we want to be doing the best we can for our colleagues, but we don't want to overload our colleagues by saying, 'By the way, not only should we be treating their skin and joints,' which of course we should be doing, but 'could you also manage their diabetes, their obesity, their disordered sleep, their anxiety, their depression, difficulties with insurance, getting access to treatments, etc.' "

"This is where effective collaboration between physicians becomes important, he stressed. "We can't manage every single piece, but we can make sure our patients are informed, are aware, and assist them to get the help that they need."

In the United States, there "is a real issue" with access to mental health care and greater awareness needs to be created around this issue, he added.

Wallace and Merola report no relevant financial relationships.

Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 Annual Meeting. No abstract. Presented July 14, 2023.

Pat Kelly is a medical journalist in Dublin, Ireland.

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