Unraveling the causative connection between urticaria, inflammatory cytokines, and mental disorders: Perspectives from genetic evidence.

Background: The genetic association between urticaria and mental disorders and whether inflammatory cytokines mediate this process remains unclear.

Materials and methods: A Mendelian randomization (MR) approaches to elucidate the causal relationship between urticaria and mental disorders and to validate the mediation of inflammatory cytokines. Genome-wide association study (GWAS) databases used were obtained from Psychiatric Genomics Cooperation (PGC), GWAS Catalog, and FinnGen Consortium. Our study was conducted using inverse variance weighted (IVW) and Bayesian weighted MR (BWMR) methods for joint analysis.

Results: The MR results showed that urticaria increased the risk of attention deficit hyperactivity disorder (ADHD) (odds ratio [OR] $=$ 1.088, 95% confidence interval [CI]: 1.026-1.154, p $=$ 0.0051); cholinergic urticaria increased the risk of bipolar disorder (BD) (OR $=$ 1.012, 95% CI: 1.001-1.022, p $=$ 0.0274); dermatographic urticaria increased the risk of ADHD (OR $=$ 1.057, 95% CI: 1.005-1.112, p $=$ 0.0323); idiopathic urticaria increased the risk of schizophrenia (SCZ) (OR $=$ 1.057, 95% CI: 1.005-1.112, p $=$ 0.0323); other unspecified urticaria increased the risk of ADHD (OR $=$ 1.085, 95% CI: 1.023-1.151, p $=$ 0.0063). We found that eight inflammatory cytokines were negatively associated with mental disorders and seven inflammatory cytokines were positively associated with mental disorders. Finally, our results suggested that inflammatory cytokines do not act as mediators between urticaria and mental disorders.

Conclusions: Our study reveals a causal relationship between urticaria and the increased risk of mental disorders. We suggest that the treatment of urticaria could incorporate psychiatric interventions and mental health assessment of patients.