BACKGROUND: Growing evidence suggests that atopic dermatitis (AD) is associated with an increased risk of depressive disorders and anxiety. However, existing studies were observational and may uncover correlations but cannot easily disentangle non-causal or reverse-causal associations because these associations could be confounded and may not reflect true causal relationships. OBJECTIVES: We carried out a 2-sample Mendelian randomization (MR) study to examine the potential effect of AD on the risk of depressive disorders and anxiety. METHODS: Genetic instruments from the largest available genome-wide association study (GWAS) for AD (10,788 cases, 30,047 controls) were used to investigate the relation to broad depression (170,756 cases, 329,443 controls), major depressive disorder (MDD) (30,603 cases, 143,916 controls) and anxiety (5,580 cases, 11,730 controls). A set of complementary approaches were carried out to assess horizontal pleiotropy and related potential caveats occurring in MR studies. RESULTS: We observed no causal impact of AD on the risk of depressive disorders and anxiety, with close-to-zero effect estimates. The inverse weighted method revealed no associations of AD on broad depression (OR=1.014, P=0.4307), probable MDD (OR=1.004, P=0.5681), ICD-9/10-based MDD (OR=1.001, P=0.4659) or anxiety (OR=1.097, P=0.1801). CONCLUSIONS: In summary, this MR study does not support a causal effect of AD on depression and anxiety.