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The present study investigated the association of depression and anxiety symptomatology (DAS) with asthma and atopic dermatitis (AD) diagnosis during mid-adult years. The study employed data from 502,641 participants in the UK Biobank. Neutrophils to Lymphocytes Ratios (NLRs) of patients with asthma and AD were calculated and evaluated in relation to DAS, measured via the Patient Health Questionnaire-4 (PHQ-4). Age of asthma or AD onset association with DAS were also estimated. Multivariable regression analyses were implemented among participants with asthma or AD, compared to those without these disorders. Out of 58,833 participants with asthma and 13,462 with AD, the prevalence of DAS was 11.7% and 2.7%, respectively. DAS increased among participants with either asthma or AD, being highest within patients having both (β = 0.41, 95% confidence interval (95%CI), 0.34,0.49). NLR showed a linear increase with PHQ scores in asthma patients, (tertile 1, β = 0.30, 95% CI, 0.27,0.34; tertile 2, β = 0.36, 95%CI, 0.32,0.39, and tertile 3, β = 0.43, 95%CI, 0.39,0.46). An inverted U-shaped association was seen between age of asthma onset and PHQ, with the 40–59 age group (β = 0.54, 95%CI, 0.48,0.59) showing the highest risk followed by the 60+ (β = 0.43, 95%CI, 0.34,0.51 and 20–39 groups (β = 0.32, 95%CI, 0.27,0.38). Similar patterns emerged within AD. Asthma and AD were associated with increased DAS during mid-adult years, being strongest among participants reporting both disorders. A dose–response relationship between NLR and DAS was observed. Asthma or AD onset during mid-adult years (40–59) were associated with the highest increment in DAS.