DUBLIN – , 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.
Dr. Wallace, of Cherry Hills Dermatology, Englewood, Colo., discussed the complex interactions between mental illness and psoriatic disease and the potential pitfalls of this comorbidity for these patients.
Dr. Joseph F. Merola
The topic of mental health is “consistently at the top of our patients’ minds, and certainly our minds too,” said session comoderator and GRAPPA president-elect Joseph F. Merola, MD, MMSc.
“In the U.S., around 17% of people with psoriasis have depression vs. 9% in those without psoriasis,” Dr. 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, Dr. 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, Dr. 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, Dr. 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.”