Association between use of systemic and inhaled glucocorticoids and changes in brain volume and white matter microstructure: a cross-sectional UK Biobank study

M. Van Der Meulen*^a (Mrs), JM. Amaya^a (Mr), OM. Dekkers^a (Prof), OC. Meijer^a (Prof)

^a Leiden University Medical Center, Leiden, NETHERLANDS

* m.vandermeulen@lumc.nl

Introduction: Chronic exposure to high levels of endogenous or exogenous glucocorticoids can lead to neuropsychiatric symptoms and is associated with changes in brain volume and white matter microstructure. However, most clinical studies investigating the effects of glucocorticoid overexposure on the brain have been performed in small, selected populations with chronic glucocorticoid excess, and it remains unknown whether these consequences can also be observed in a general sample of people using glucocorticoids, including inhaled glucocorticoids. Therefore, we investigated whether systemic or inhaled glucocorticoid use are associated with changes in grey matter volumes and white matter microstructure in the population-based cohort of the UK Biobank.

Material and methods: In this cross-sectional study, imaging data from the UK Biobank were available for 222 systemic glucocorticoid users, 557 inhaled glucocorticoid users, and 24106 controls after exclusion based on neurological, psychiatric, or endocrine history, and use of psychotropic medication. Primary outcomes were differences in 22 volumetric and 14 diffusion imaging parameters between glucocorticoid users and controls, determined using linear regression analyses adjusted for potential confounders. Secondary outcomes included cognitive functioning (six tests) and emotional symptoms (four questions).

Results: Both systemic and inhaled glucocorticoid use were associated with reduced white matter integrity (lower fractional anisotropy and higher mean diffusivity), with larger effect sizes in systemic users than inhaled users, and largest effect sizes in chronic systemic glucocorticoid users. In addition, systemic glucocorticoid use was associated with larger volumes of the caudate nucleus, while inhaled glucocorticoid users had smaller amygdala volumes. As for secondary outcomes, systemic glucocorticoid users scored significantly lower on one cognitive task (symbol digit substitution) and both systemic and inhaled glucocorticoid users had significantly worse scores on all four investigated emotional outcomes (depression, disinterest, tenseness, and tiredness), compared to controls.

Discussion: In conclusion, both systemic and inhaled glucocorticoid use are associated with decreased white matter integrity and limited volumetric changes in several brain regions. These effects may contribute to the neuropsychiatric side effects of glucocorticoid medication, especially with chronic use.

The author has declared no conflict of interest.