The use of both systemic and inhaled glucocorticoids appears to be associated with changes in the structure and volume of white matter in the brain, according to a cross-sectional study published in BMJ Open.

To investigate the association between glucocorticoid use and brain structure changes, researchers used data from the UK Biobank, a large population-based, prospective cohort that included over 500,000 participants between the ages of 40 and 69 years at the time of study recruitment (2006 to 2010).

After excluding individuals with neurological conditions, psychiatric disease history, and those on psychotropic medications, they identified 222 patients on systemic glucocorticoids and 557 patients on inhaled glucocorticoids who had both T1-weighted MRI and diffusion tensor imaging data available at the same imaging visit.

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The primary endpoint of the study was the difference in volumetric and diffusion imaging parameters between glucocorticoid users and controls (n=24,106). Cognitive functioning and emotional symptoms were explored as secondary outcomes.

Findings showed that glucocorticoid use (both systemic and inhaled) was associated with less intact white matter structure when compared with nonuse, based on a comparison of MRI scans. The effect was found to be greater in participants on systemic glucocorticoids and in long-term users. When compared with controls, the caudate was found to be larger in systemic glucocorticoid users, while the amygdala was observed to be smaller in inhaled glucocorticoid users.

Additionally, individuals taking systemic glucocorticoids performed worse on the symbol digit substitution task (a test designed to measure processing and speed) and reported significantly more depressive symptoms, apathy, restlessness and fatigue, compared with nonusers.

“This study shows that both systemic and inhaled glucocorticoids are associated with an apparently widespread reduction in white matter integrity, which may in part underlie the neuropsychiatric side effects observed in patients using glucocorticoids,” the study authors concluded. They did note that formal conclusions on causality could not be made due to the cross-sectional nature of the study.


  1. Steroid meds linked to structural and volume changes in brain white and grey matter. News release. Accessed August 30, 2022.
  2. van der Meulen M, Amaya JM, Dekkers OM, et al. Association between use of systemic and inhaled glucocorticoids and changes in brain volume and white matter microstructure: a cross-sectional study using data from the UK Biobank. Published online August 30, 2022. BMJ Open. doi:10.1136/ bmjopen-2022-062446

This article originally appeared on MPR