Inhaled, Systemic Glucocorticoid Use May Affect White Matter Integrity

Systemic and inhaled glucocorticoids may have detriments to white matter integrity, according to study findings published in BMJ Open.

Glucocorticoids are the most prescribed medications on the market. These drugs have been associated with adverse effects to metabolic, cardiovascular, and musculoskeletal systems as well as causing neuropsychiatric symptoms.

To evaluate the effects of glucocorticoids on brain structure, data for this study were sourced from the UK Biobank. Individuals (N=28,888) who had magnetic resonance and diffusion tensor imaging data were evaluated for differences in volumetric and diffusion imaging parameters as well as cognitive functioning and emotional symptoms on the basis of glucocorticoid use.

Participants had not been exposed to glucocorticoids (n=24,106) or used inhaled glucocorticoids (n=557) and systemic glucocorticoids (n=222). The cohorts included 45.4%-50.4% men, aged mean 63.3-66.1 years, and 48.6%-51.5% had a college degree.

Compared with control individuals, the systemic glucocorticoid users differed significantly for caudate gray matter volume (adjusted mean difference [aMD], 178.7 mm³; 95% CI, 82.2-275.0; P =1.0×10^-4), global mean diffusivity (aMD, 7.2×10^-6; 95% CI, 3.2x 10^-6-1.1×10^-5; P =1.0×10^-4), global fractional anisotropy (aMD, -0.0037; 95% CI, -0.0064 to -0.0010; P =4.2×10^-3), and caudate subcortical volumes (aMD, 77.8 mm³; 95% CI, 24.5-131.1; P =.0023).

For the inhaled glucocorticoid users, they differed from control individuals in amygdala gray matter (aMD, -23.9 mm³; 95% CI, -41.5 to -6.2; P =5.2×10^-3), global fractional anisotropy (aMD, -0.0023; 95% CI, 24.5-131.1; P =5.7×10^-3), and global mean diffusivity (aMD, 2.7×10^-6; 95% CI, 1.7x 10^-6; 95% CI, 1.7x 10^-7-5.2×10^-6, P =.034).

The systemic glucocorticoid users performed poorer than the unexposed cohort in the symbol substitution cognitive evaluation (aMD, -0.17; 95% CI, -0.34 to -0.01; P =.04).

Systemic glucocorticoid users were more likely than control individuals to experience tiredness (odds ratio [OR], 1.90; 95% CI, 1.45-2.50; P =4.4×10^-6), disinterest (OR, 1.84; 95% CI, 1.29-2.56; P =5.1×10^-4), tenseness (OR, 1.78; 95% CI, 1.29-2.41; P =3.0×10^-4), and depression (OR, 1.76; 95% CI, 1.25-2.43; P =8.2×10^-4). Inhaled glucocorticoid users were at increased risk for tiredness compared with control individuals (OR, 1.35; 95% CI, 1.14-1.60; P =6.3×10^-4).

This study may have been limited by excluding individuals with established psychological conditions. It remains unclear whether glucocorticoid use may affect this patient population differently than the general population.

“While it remains unclear whether the observed effect sizes have clinical consequences for the population of glucocorticoid users as a whole, these findings are remarkable given the common neuropsychiatric side effects of synthetic glucocorticoids, and the observed changes may play a role in those patients suffering from these side effects,” the researchers stated.

They added, “This study shows that both systemic and inhaled glucocorticoids are associated with an apparently widespread reduction in white matter integrity, which may in part underly the neuropsychiatric side effects observed in patients using glucocorticoids.”

The researchers emphasized that further research is warranted to assess the underlying mechanisms, reversibility, and risk factors for the development of neuropsychiatric side effects from glucocorticoids.

Disclosure: An author declared affiliations with industry. Please refer to the original article for a full list of disclosures.