Depression in Psoriasis: Genetic Background, Metabolic, and Inflammatory Factors

Principal Investigator: Mona Stahle, M.D.
Institution: Karolinska Institutet

Grant Mechanism: More Than Skin Deep: Mental Health Grant
Funding Amount: $100,000
Project Start Date: August 1, 2023
Project End Date: December 31, 2024
Status: Active
Keywords: Psoriasis, Comorbidity, Biomarkers, Genetics, Inflammation, Mental Health, Multi-omics, Basic Science, Clinical Research

Project Summary:

Persons with psoriasis have high risk of depression. The reasons for this are unknown, but explanations include shared heritability, inflammation inside the body ("systemic inflammation"), and alterations in chemical reactions converting nutrients to other molecules ("metabolism"). The tryptophan pathway is a metabolic process that may be of particular importance here as it interacts with inflammation and is important for both psoriasis and depression. Data on the relationships between genetics, systemic inflammation, and the tryptophan pathway and their impacts on depression may help us understand the excess risk of depression in psoriasis. This could lead to new treatments addressing both psoriasis and depression. We seek to analyze blood and other data from two studies on a total of 1,800 patients with psoriasis who have been followed for up to 20 years and have complete data on diagnoses of depression in specialist outpatient and inpatient settings.

How will your project help improve the lives of the 125 million affected by psoriatic disease?

The main object of our research is to understand the wide spectrum of clinical variants of psoriatic disease and their molecular and genetic background. How do different forms of psoriasis evolve over time, who will get severe disease, and who will have a mild disease course? Who is at risk to develop severe comorbidities such as psoriatic arthritis, depression, and cardiovascular disease, and could early treatment modify or even prevent such complications? Identifying predictors would be a major help in tailoring treatment and alert lifestyle modifications. Would it even be possible to change the disease course? Effective management and recognition of depression is an unmet need in psoriasis. A deeper understanding of the role of inflammation in depression could be a game-changer for patients affected and may pave the way for the development of new treatments.

Why is psoriatic disease research important to you, personally? What role will this award play in your research efforts or career development?

Psoriasis is a fascinating disease. A human companion since historic times where evolutionary changes have promoted an immune profile that in addition to survival carries the risk to develop psoriasis. So in my mind, the history of psoriasis is closely linked to the history of human immune development. As an enigma, it contains all challenges and has proven to be so much more than skin lesions - affecting the heart and the brain. I could not imagine a more interesting scenario. And during the past years, we have witnessed formidable progress in its treatment that while offering tremendous help for the patients also teaches us about the disease. I am in the late stage of my career but am so grateful for this opportunity to hopefully add a few exclamation marks in our understanding of psoriasis.

Researcher Profile:

Mona Stahle is a professor of Dermatology at Karolinska Institutet/Stockholm, Sweden. She is an M.D. and specialist in Dermatology and received her clinical training at Karolinska. Following her Ph.D. at Karolinska, she went for a 2-year post-doc at Washington University, MO, USA where she received basic laboratory training applying molecular biology methods to explore skin biology. At Karolinska, she established a platform for studies on skin inflammation building large cohorts of patients with detailed clinical data and long-term follow-up with a focus on psoriasis. She has published almost 200 scientific papers In recognition of her work she has received several prizes among which the Jubilee Prize from the Swedish Royal Medical Society. Fifteen Ph.D. students have obtained their degree under her supervision and many postdocs trained in her laboratory, three of whom are today full professors. She served as head of the Dermatology Department at Karolinska for many years.