(MBRC) Psoriasis, psoriatic arthritis and suicide: Is there a link?

Psoriasis is currently an incurable, chronic, immune-mediated disease affecting almost 3% of people in the United Kingdom (UK). It is widely regarded as a systemic inflammatory disease given its association with a number of co-morbidities including psoriatic arthritis (PsA), which affects ~100 000 people in the UK, cardiovascular disease and metabolic syndrome.

Depression is overrepresented in both psoriasis and PsA, and patients may experience significant disease-related distress, including suicidal ideation (Chisholm et al, 2016). There is an expanding literature linking depression with inflammation; emerging evidence from studies of people with major depressive disorder (MDD) suggests that neuroinflammation of the brain may be particularly pronounced in those with suicidal thinking (Holmes et al, 2018).

We previously investigated patients with chronic plaque psoriasis without comorbid PsA, depression, suicidality or evidence of raised circulating inflammatory markers (C-reactive protein [CRP], interleukin-6 [IL-6]), and did not find evidence of neuroinflammation as compared to healthy volunteers (Hunter et al, 2016). An insufficient inflammatory burden to induce neuroinflammation in the studied psoriasis patients could explain this lack of difference with the control group.

There remains an urgent need to investigate patients with psoriasis and PsA who present with depression and suicidality, to ensure appropriate therapies and interventions are considered. Furthermore, reports of a purported association between both small molecule and biologic therapies, widely used for severe psoriasis and PsA, and risk of depression and suicidality, pose a significant clinical dilemma for clinicians and patients.

We propose to firstly, undertake a cross-sectional survey to investigate prevalence of depression and suicidality in patients with moderate to severe: (i) psoriasis; (ii) PsA; (iii) co-existent psoriasis and PsA in tertiary referral clinics. Secondly, we shall ascertain whether the brains of patients with psoriasis, as well as coexistent PsA and depression, exhibit higher levels of neuroinflammation, as evidenced by activated microglia, as compared to both healthy controls and patients with psoriasis without comorbid disease.
Understanding the underlying neurocognitive mechanisms which mediate the adverse consequences of psoriasis and PsA such as low mood and suicidality is critical to moving the field forward. (338/400)