Glucocorticoids May Decrease White Matter Integrity & Change Gray Matter Volume

Subjects with a history of neurologic conditions or psychiatric disease, and those taking psychotropic medication were excluded from the study. Of note, “those with the psychiatric conditions most commonly associated with glucocorticoid use (i.e., anxiety, depression, mania and delirium) were studied so as not to exclude patients based on potentially glucocorticoid-related outcomes.”¹

Patients in the control group (n=24,106) included those who met the above criteria but hadn’t used glucocorticoids at any time point prior to or during imaging. These patients also didn’t have an endocrine disorder. The groups didn’t differ significantly with respect to sex, education or smoking status. However, the systemic glucocorticoid group was slightly older than the inhaled glucocorticoid group, and the inhaled glucocorticoid group had a higher body mass index and body fat percentage than the systemic glucocorticoid group. 

Both systemic and inhaled glucocorticoid use were associated with reduced white mater integrity compared with controls, with larger effect sizes in systemic glucocorticoid users. “If white matter integrity is reduced, this indicates that connections between brain regions essential for integrating information may be impaired,” says Dr. Van der Meulen.

Systemic glucocorticoid use was also associated with larger caudate gray matter volume. Inhaled glucocorticoid users had smaller amygdalas than controls. 

For secondary outcomes, systemic glucocorticoid users performed worse on the symbol digit substitution task, which assesses complex processing speed. They also reported more depressive symptoms, disinterest, tenseness/restlessness and tiredness/lethargy compared with controls.  Inhaled glucocorticoid users only reported more tiredness/lethargy. Of note, the authors write that “the observed mood-related effects may not be caused by glucocorticoid use per se but could also be related to the condition for which glucocorticoids were prescribed.”

Limitations: The cross-sectional nature of this study doesn’t permit formal conclusions on causality. Data regarding the dose and duration of glucocorticoid use aren’t available in the U.K. Biobank. Thus, thorough analyses on dose- or duration-dependent effects weren’t possible.

Dr. Van der Meulen

Implications for Clinical Practice

Dr. Van der Meulen was kind enough to share her take on the clinical implications of this fascinating research.

The Rheumatologist (TR): What do you think is the most interesting part of your research?

Dr. Van der Meulen: The finding that struck our research team most was the widespread reduction in white matter integrity that we found consistently in the brain regions that we studied. Historically, much research has focused on the effects of glucocorticoids on neurons, but this study adds to a growing body of evidence showing that an important part of glucocorticoid effects on the brain may be mediated by the glial cells in the white matter.