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All in the mind - psoriasis and depression

It is well known that depression is common in those with psoriasis.  In fact, of all conditions that co-occur with psoriasis, depression is the most common, affecting up to 80% of patients with the condition1,2. Depression not only makes life miserable for sufferers; it increases the risk of psoriatic arthritis and worsens treatment outcomes and prognosis3,4.  Of course, it isn’t surprising that depression should be so common in people with psoriasis, given that they are living with a condition that is physically uncomfortable, can limit physical activities and often results in embarrassment and stigmatization.  However, recent evidence suggests that this is only a part of the story and there is another key factor involved: inflammation.  In other words, both psoriasis and depression have common underlying mechanisms. 

Inflammation the key

Inflammation and immunity are regulated by a special group of proteins called cytokines, including interleukins and tumour necrosis factor-alpha (TNF-alpha)5. The combined effects of these cytokines account for the various clinical features of psoriasis and psoriatic arthritis, and their serum levels are strongly associated with disease severity.  In fact, psoriasis has been described as the result of a cytokine ‘storm’ 6.  Importantly, these inflammatory molecules can cross the blood-brain barrier where they may deplete a variety of neurotransmitters, including serotonin, norepinephrine and dopamine – all of which are intimately involved in mood regulation and mental functioning. 

Strong confirmation of this association has come from a recent study which examined the relationship between depression severity and serum levels of inflammatory cytokines in 18 in men with psoriasis7.  Depression severity correlated positively with psoriasis duration, the Psoriasis Area Severity Index (PASI) score, the percentage of body surface area affected by psoriatic lesions, and serum interleukin-18 concentration.  In addition, depression severity correlated negatively with 25-hydroxyvitamin D3 concentration.

The impact of biologics on depression

Biologic drugs, or "biologics," used to treat psoriasis are given by injection or intravenous (IV) infusion.  Examples include; infliximab; adalimumab and etanercept.  These drugs target specific parts of the immune system and block the adverse effects of inflammatory cytokines – especially TNF-alpha and various Interleukins. By calming inflammation throughout the body, biologics might be expected to not only improve skin lesions and arthritis in psoriasis, but also symptoms of depression.  Anecdotally, this appears to be the case given that in clinical trials, it is common for participants to report improvements in mood, well before the benefits are seen in the skin.   Moreover, this observation is borne out by a growing body of scientific evidence.  For example. a recent study on the impact of TNF-Alpha inhibitors in a total of 980 patients with psoriasis or psoriatic arthritis, found a significant improvement in rates of depression and insomnia after biologic therapy and a reduction of around 40% in the use of antidepressants8. 

In addition, a systematic review of relevant studies also confirmed a significant improvement in depressive symptoms in psoriatic patients taking a range of biologic agents9.  

Treatment implications

Inflammation is the key factor underlying both psoriasis and depression; the more severe the psoriasis, the more marked the depression.  Given the substantial beneficial impact of biologics on both the physical and psychological manifestations of psoriasis, it is clear that their use should be considered earlier rather than later.  There may also be benefit in recommending oral vitamin D supplementation10. 

In the US, the National Psoriasis Foundation (NPF) has published their “Treat to Target” initiative, which aims to reduce psoriasis to no more than 1 percent of body surface area after three months of treatment11.  NICE has issued similar guidelines for the UK, though access to specialist centres for systemic therapy may be difficult12. 

Key points

  • Psoriasis has both physical and psychological manifestations, both of which are mediated by a range of inflammatory cytokines.
  • Depression is associated with both the severity of the psoriasis and serum levels of inflammatory markers.
  • Systemic therapy with biologics improves both physical and psychological manifestations of psoriasis
  • Treatment with biologics should therefore be considered earlier rather than later in patients with moderate-severe psoriasis.
  • Vitamin D supplementation may be a useful adjunct in patients with psoriasis

Dr David Ashton MD PhD

Scientific References

  1. Connor CJ, Liu V, Fiedorowicz JG. Exploring the physiological link between psoriasis and mood disorders. Dermatol Res Pract. 2015; 2015: 409637. https://doi.org/10.1155/2015/409637 PMID: 26550011
  2. Lewinson RT, Vallerand IA, et al. Depression Is Associated with an Increased Risk of Psoriatic Arthritis among Patients with Psoriasis: A Population-Based Study. J Invest Dermatol. 2017; 137: 828–35.
  3. Korman AM, Hill D, Alikhan A, Feldman SR. Impact and management of depression in psoriasis patients. Expert Opin Pharmacother. 2016;17: 147–52.
  4. Lakshmy S, Balasundaram S, Sarkar S, Audhya M, Subramaniam E. A cross-sectional study of prevalence and implications of depression and anxiety in psoriasis. Indian J Psychol Med. 2015;37: 434–40. 
  5. Carrascosa JM, Rocamora V, Fernandez-Torres. Obesity and psoriasis: inflammatory nature of obesity, relationship between psoriasis and obesity, and therapeutic implications. Actas Dermosifiliogr. 2014;105:31-44.
  6. Baliwag J, Barnes DH, and Johnston A. Cytokines in psoriasis. Cytokine. 2015; 73: 342–350.
  7. Pietrzak D, Pietrzak A, Grywalska E et al. Serum concentrations of interleukin 18 and 25-hydroxyvitamin D3 correlate with depression severity in men with psoriasis. PLoS One. 2018; 13: e0201589. doi: 10.1371/journal.pone.0201589.
  8. Wu CY, Chang YT, Juan CK, et al. Depression and Insomnia in Patients with Psoriasis and Psoriatic Arthritis Taking Tumor Necrosis Factor Antagonists Medicine (Baltimore) 2016 May; 95(22): e3816. Published online 2016 Jun
  9. Fleming P, Roubille C, Richer V et al. Effect of biologics on depressive symptoms in patients with psoriasis: a systematic review. J Eur Acad Dermatol Venereol. 2015; 29:1063-70.
  10. Wenyang Fu L, Vender R, Systemic Role for Vitamin D in the Treatment of Psoriasis and Metabolic Syndrome. Dermatol Res and Pract Volume 2011, Article ID 276079, 4 pages doi:10.1155/2011/276079
  11. Psoriasis: assessment and management. Clinical guideline [CG153] Published date: October 2012 Last updated: September 2017.  https://www.nice.org.uk/guidance/cg153/chapter/1-Recommendations#systemic-therapy
  12. Armstrong AW, Siegel MP, Bagel J et al. From the Medical Board of the National Psoriasis Foundation: Treatment targets for plaque psoriasis. J Am Acad Dermatol.2017; 76:290-298
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