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Inhaled glucocorticoids associated with changes in brain substance
Due to their immunosuppressive properties, systemic glucocorticoids are estimated to be used annually by 0.5% to 3% of the population. Glucocorticoids are effective, but their use is associated with some significant musculoskeletal and cardiovascular side effects. A recently opened BMJ study conducted a cross-sectional analysis to test the hypothesis that the use of systemic and inhaled glucocorticoids was associated with changes in gray matter volume (GMV) and white matter microstructure. Learning: Association between systemic and inhaled glucocorticoid use and changes in brain volume and white matter microstructure: a cross-sectional study using UK Biobank data. …
Inhaled glucocorticoids associated with changes in brain substance
Due to their immunosuppressive properties, systemic glucocorticoids are estimated to be used annually by 0.5% to 3% of the population. Glucocorticoids are effective, but their use is associated with some significant musculoskeletal and cardiovascular side effects. A recent one BMJ opened Study conducted a cross-sectional analysis to test the hypothesis that the use of systemic and inhaled glucocorticoids was associated with changes in gray matter volume (GMV) and white matter microstructure.
background
In addition to the physical side effects mentioned above, the use of synthetic glucocorticoids could lead to neuropsychiatric symptoms such as depression, mania and even a significantly increased suicide (attempt) rate. Previous studies have shown that excessive exposure to glucocorticoids has adverse effects on the brain. Some studies have documented reductions in the volume of certain regions of the brain, including the amygdala and hippocampus, in patients receiving high doses of synthetic systemic glucocorticoids.
In patients with Cushing's disease, long-term glucocorticoid excess is associated with cerebral atrophy and reduced cortical thickness. A reduction in white matter integrity throughout the brain has also been reported in such patients. Diffusion tensor imaging (DTI) analysis showed globally reduced fractional anisotropy (FA), a marker of microstructural architecture.
Most studies on the effects of glucocorticoid overexposure have been conducted in small, selected populations. However, it remains to be seen whether these results apply to a broader sample of individuals using glucocorticoids, including inhaled glucocorticoids.
About studying
A large population-based cohort study was conducted using data from the UK Biobank to address the above research gap. The hypothesis was that differences in white matter microstructure and brain volume could be identified between nonusers and users of inhaled or systemic glucocorticoids. The study recruited adults between 2006 and 2010, and exclusion conditions focused on endocrinological, psychiatric or neurological history and use of psychotropic medications. The study included 557 users of inhaled glucocorticoids, 222 users of systemic glucocorticoids and 24,106 controls.
The study assessed not only cognitive outcomes, but also differences in emotional well-being and cognitive function. The researchers hypothesized that the use of glucocorticoids would result in decreased gray matter volume in the limbic system and hippocampus, decreased fractional anisotropy (FA), and increased mean diffusivity (MD) throughout the brain, as well as poorer cognitive and emotional functions.
Key insights
Systemic and inhaled glucocorticoids were observed to be associated with changes in several brain imaging parameters. In addition, the present study also detected glucocorticoid effects on white matter microstructure that were reported in previous studies.
The use of inhaled and systemic glucocorticoids has been found to be associated with reduced white matter integrity. In other words, lower FA and higher mean diffusivity (MD) were observed compared to controls. Based on this observation and the fact that a large sample size was taken into account, it could be concluded that the adverse effects of glucocorticoids were quite widespread.
Chronic use of glucocorticoids showed a duration- or dose-dependent effect on white matter microstructure. The most significant effects were observed in chronic systemic glucocorticoid users, somewhat significant effects were observed in systemic glucocorticoid users and the least effects were observed in the case of inhaled glucocorticoid users. The findings are important because synthetic glucocorticoids have common neuropsychiatric side effects and may help treat patients who report them.
Strengths and limitations of the current study
The main strength of this study is the large sample size. According to the authors, this is the most comprehensive study to date on the connection between glucocorticoids and brain structure. It is also the first to examine such relationships in users of inhaled glucocorticoids. Additionally, strict exclusion criteria were used to mitigate the effects of confounding factors.
The main limitation of the study is related to its cross-sectional nature, which precludes causal conclusions. Furthermore, duration or dose-dependent associations could not be analyzed thoroughly due to the lack of data in the UK Biobank.
Concluding remarks
Large-scale cross-sectional analysis revealed that inhaled and systemic glucocorticoid use was associated with reduced white matter integrity and limited changes in gray matter volume. This finding led researchers to conclude that such an association may contribute to the neuropsychiatric side effects of glucocorticoid medications, and this may be more pronounced in chronic users.
Reference:
- van der Meulen, M. T. et al. (2022) Assoziation zwischen der Anwendung von systemischen und inhalativen Glukokortikoiden und Veränderungen des Gehirnvolumens und der Mikrostruktur der weißen Substanz: eine Querschnittsstudie unter Verwendung von Daten der UK Biobank. BMJ Open.12:e062446. doi:10.1136/ bmjopen-2022-062446, https://bmjopen.bmj.com/content/12/8/e062446
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