Journal of dermatological science · 2026
Unsaturated fatty acids mediate the bidirectional link between psoriasis and depression: Evidence from observational and mendelian randomization studies.
СтатьяНаблюдательное исследованиеНазвание и аннотация: Перевод в очереди
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Chu Mengyang, Tian Biqing, Zhou Jian, Xu Guangquan, Gu Yunfeng, Wang Jiaqi, Hao Junfeng, Dang Erle, Shao Shuai, Wang Gang
Аннотация
BACKGROUND: Depression is a prevalent and debilitating comorbidity of psoriasis. While the epidemiological association between the two conditions is well established, the causal relationship and the underlying biological mechanisms remain insufficiently understood.
OBJECTIVES: To evaluate the causal association between psoriasis and depression, as well as the mediating function of circulating unsaturated fatty acids (UFAs).
METHODS: We combined cross-sectional analysis of 211 psoriasis patients, high-throughput serum metabolomics, and bidirectional Mendelian randomization (MR) using large-scale genome-wide association studies (9267 psoriasis cases; 170,756 depression cases). Multivariable MR analyses were adjusted for body mass index (BMI) and smoking. Two-step MR mediation was used to assess the role of UFA phenotypes.
RESULTS: Clinically significant depressive symptoms (PHQ-9 ≥ 10) were present in 32.7% of patients and were independently associated with higher BMI, smoking, special site involvement, and higher PASI scores. MR analyses indicated a robust bidirectional causal relationship between psoriasis and depression, independent of BMI and smoking. Serum metabolomics revealed reduced omega-3 PUFAs (DHA, DPA, ETA) and elevated MUFAs in psoriasis patients with depression. Mediation MR identified the DHA-to-total fatty acid ratio as a key causal intermediary from psoriasis to depression, whereas depression liability altered PUFA/MUFA ratios to promote psoriasis risk.
CONCLUSIONS: Our integrative approach reveals a causal, bidirectional link between psoriasis and depression and indicates that unsaturated fatty acid imbalance, particularly reduced omega-3 PUFAs, may serve as a potential mediating mechanism. These findings highlight modifiable intervention targets, including weight management, smoking cessation, and omega-3 supplementation, may help to simultaneously improve dermatologic and psychiatric outcomes.
OBJECTIVES: To evaluate the causal association between psoriasis and depression, as well as the mediating function of circulating unsaturated fatty acids (UFAs).
METHODS: We combined cross-sectional analysis of 211 psoriasis patients, high-throughput serum metabolomics, and bidirectional Mendelian randomization (MR) using large-scale genome-wide association studies (9267 psoriasis cases; 170,756 depression cases). Multivariable MR analyses were adjusted for body mass index (BMI) and smoking. Two-step MR mediation was used to assess the role of UFA phenotypes.
RESULTS: Clinically significant depressive symptoms (PHQ-9 ≥ 10) were present in 32.7% of patients and were independently associated with higher BMI, smoking, special site involvement, and higher PASI scores. MR analyses indicated a robust bidirectional causal relationship between psoriasis and depression, independent of BMI and smoking. Serum metabolomics revealed reduced omega-3 PUFAs (DHA, DPA, ETA) and elevated MUFAs in psoriasis patients with depression. Mediation MR identified the DHA-to-total fatty acid ratio as a key causal intermediary from psoriasis to depression, whereas depression liability altered PUFA/MUFA ratios to promote psoriasis risk.
CONCLUSIONS: Our integrative approach reveals a causal, bidirectional link between psoriasis and depression and indicates that unsaturated fatty acid imbalance, particularly reduced omega-3 PUFAs, may serve as a potential mediating mechanism. These findings highlight modifiable intervention targets, including weight management, smoking cessation, and omega-3 supplementation, may help to simultaneously improve dermatologic and psychiatric outcomes.