Introduction: Use of local corticosteroids, especially the inhaled types, has increasingly been associated with systemic uptake and consequent adverse events. In this study, we assessed the associations between different corticosteroid types with cognitive neuropsychiatric effects as related to high glucocorticoid exposure.

Methods: In 83,592 adults (mean age 42 years, 59% women) of the general population (Lifelines Cohort Study), we analyzed the relationship between corticosteroid use with executive cognitive functioning (Ruff Figural Fluency Test), and presence of mood and anxiety disorders (MINI survey). We performed additional explorations for effects of physical quality of life (QoL; RAND-36), and inflammation (high-sensitive CRP).

Results: Overall, cognitive scores were lower among corticosteroid users in comparison to nonusers (mean, 79.9 [SD, ±23.4] versus 81.5 [±23.3], P<.001). Adjustments for covariates revealed persistently lower scores in single-type users of systemic (-2.6 [95% CI, -5.0 to -0.1], P=.044) and inhaled corticosteroids (-2.1 [95% CI, -2.8 to -1.3], P<.001). Users of inhaled types showed persistently lower cognitive scores irrespective of physical QoL, psychiatric disorders, and high-sensitive CRP. Overall corticosteroid use was also associated with higher likelihood for mood and/or anxiety disorders. The strongest associations were found for inhaled corticosteroid users, whom were more likely to have mood disorders (odds ratio [OR], 1.40 [95% CI, 1.19 to 1.65], P<.001) and anxiety disorders (OR, 1.19 [95% CI, 1.07 to 1.33], P=.002) in comparison to nonusers. These findings were independent of physical QoL. Within single-type users, a higher likelihood for mood disorders was also found for systemic users whereas nasal and dermal users were more likely to have anxiety disorders.

Conclusions: Commonly used local corticosteroids, in particular inhaled types, and systemic corticosteroids are associated with reduced executive cognitive functioning and a higher likelihood of mood and anxiety disorders in the general adult population.