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This study, integrating clinical assessments with transcriptomic and metabolomic analyses, hypothesizes that TYK2 (tyrosine kinase 2) inhibitors possess a dual therapeutic potential to simultaneously address both dermatological manifestations of psoriasis and the frequently accompanied depressive symptoms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a cohort of 298 psoriasis patients evaluated using the Hospital Anxiety and Depression Scale (HADS), participants were categorized into a TYK2 inhibitor group, a Janus kinase (JAK) inhibitor group, and a non\u2010JAK pool (comprising interleukin [IL]\u201023 biologics, IL\u201017 biologics, and other treatments) to avoid overlapping JAK pathway inhibition. Statistical analysis was conducted using generalized linear models (GENMOD), with adjustments for the following covariates: age, sex, Psoriasis Area and Severity Index (PASI), body surface area (BSA), prior systemic or biologic therapy within 12\u2009months, disease duration, and phototherapy history.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      For HADS\u2010D scores, the TYK2 inhibitor group showed significantly lower values compared with the non\u2010JAK pool (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u20091.23, 95% confidence interval [CI]: 0.37\u20132.10). However, no significant differences were observed when compared with the IL\u201023 biologics group (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u20090.67, 95% CI: \u22120.76\u20132.10) or the JAK inhibitor group (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u20090.84, 95% CI: \u22121.54\u20133.21). Transcriptomic analysis of peripheral blood revealed significant downregulation of genes related to the IL\u20106 receptor, long\u2010term depression pathways, and Th17 cell differentiation, while pathways associated with neuronal activity were upregulated. Metabolomic profiling highlighted a decrease in kynurenic acid, which is known for its pro\u2010inflammatory and depressive effects, and an increase in 1H\u2010indole\u20103\u2010propanoic acid, an anti\u2010inflammatory metabolite with neuroprotective properties. It is important to note that these findings are based on exploratory omics analyses, for which false discovery rate (FDR) control was applied.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings provide a hypothesis that TYK2 inhibitors disrupt the persistent \u201cperipheral inflammation\u2013central depression\u201d cycle by targeting the IL\u201023\/Th17 axis and modulating the IL\u20106\/tryptophan metabolic hub. This innovative, multi\u2010targeted approach represents a possibility for treating psoriasis with comorbid depression, offering not only clinical improvements in both skin and mood symptoms but also enhanced patient adherence to treatment regimens.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ijd.70230","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T14:11:41Z","timestamp":1768227101000},"page":"1203-1214","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["TYK2 and IL\u201023 Pathway Therapies in Psoriasis: Associations With IL\u20106, Tryptophan Metabolism, and Depressive Symptoms"],"prefix":"10.1111","volume":"65","author":[{"given":"Lanmei","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Dermatology Huashan Hospital Affiliated with Fudan University  Shanghai 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