Potential Causal Relationship Identified Between Depression, Psoriasis

There is a potential causal link between psoriasis and depression, according to new findings, highlighting the value of mental health screening among patients with the skin disease.1

Such findings on the association between mental health and psoriasis resulted from a recently published analysis by investigators such as Xixing Ma, MD, from the Second Hospital of Hebei Medical University (HBMU). In this analysis, Ma and coauthors pointed to prior speculation suggesting inflammation may function as a pathophysiological association between psoriasis and depression.2

Most current studies on the topic, however, were described as observational research-based. They also highlighted such studies’ limited sample sizes and consequent susceptibility to potential confounding variables or reverse causality.

“Our study represents the first comprehensive investigation using MR methodology to establish the causal relationship between PSO and depression, addressing a critical gap in the current literature and potentially informing more targeted therapeutic strategies,” Ma and colleagues wrote.1 “Therefore, our study aims to explore the causal relationship between PSO and depression using a two-sample MR approach.”

Design and Notable Findings

The investigative team set out to evaluate psoriasis's potential causal connection with depression, applying a 2-sample Mendelian randomization (MR) framework to explore the subject. Their study was conducted in accordance with the 3 fundamental MR assumptions, the first of which being the instrumental genetic variants must show a significant link with the exposure (psoriasis). Additionally, Ma et al noted they must be independent of confounding variables that could affect both exposure and outcome, and they must influence the mental health outcome exclusively via exposure rather than through alternative biological pathways, thereby avoiding horizontal pleiotropy.

To assess the genetic correlation between psoriasis and depression, Ma and coauthors analyzed Z-score–based summary statistics from several genome-wide association studies (GWAS). These studies were done in European cohorts. Only GWAS datasets that met the investigative team's predefined criteria were highlighted, including consistent ancestral backgrounds, larger sample numbers, and a lack of overlap between the psoriasis and depression samples. These datasets were included to minimize bias and strengthen any causal inference.

Ma and colleagues utilized genetic variants as instrumental variables within their MR design, with the inverse variance weighted (IVW) method functioning as the principal analytical approach. Additionally, the investigative team supplemented this with MR Steiger testing for the purposes of confirming causality's direction. It was also supplemented with colocalization analyses as the team sought to explore whether both traits share any underlying causal variants.

These data demonstrated a link between genetic liability to psoriasis and an elevated depression risk (OR 1.35, 95% CI 1.14–1.59, P = .004). This association identified by Ma et al was shown to have been consistent across several complementary MR approaches. These approaches included MR-Egger and MR-PRESSO. In findings resultinf from directionality testing via MR Steiger, a causal influence of psoriasis on depression was identified. Additionally, the investigators' colocalization analysis pointed to rs12189871 as a shared causal locus implicated in both of the phenotypes.

Growing interest in any links between psoriasis and mental health outcomes like depression has prompted a variety of previous investigations, and Ma and colleagues' findings contribute additional evidence supporting a causal relationship between the inflammatory skin disease and depression. While the underlying biological mechanisms were still described by the investigators as not yet elucidated, previous data has indicated that genetic variation involving the HLA-C region may heighten a patient's susceptibility to depressive symptoms.

“Future research should focus on elucidating the underlying biological mechanisms, particularly the role of shared inflammatory pathways and specific genetic loci such as those within the HLA region identified in our study,” they concluded.1

References

1. Guo Bingshen, Bai Yanzhi, Ma Xixing, et al. Genetic Susceptibility to Psoriasis Increases Risk of Depression: Evidence From a Mendelian Randomization Study, International Journal of Clinical Practice, 2025, 9238266, 8 pages, 2025. https://doi.org/10.1155/ijcp/9238266.

2. Bell KA, Balogh EA, Feldman SR. An update on the impact of depression on the treatment of psoriasis. Expert Opin Pharmacother. 2021 Apr;22(6):695-703. doi: 10.1080/14656566.2020.1849141. Epub 2020 Nov 16. PMID: 33198529.