Prescribed steroids linked to changes in brain white and grey matter 

The use of systemic glucocorticoids is associated with changes in brain imaging parameters that may help explain the steroid long term neuropsychiatric side effects, new research suggests.

In a UK study, significant changes in grey matter volume (GMV) and white matter microstructure were seen on T1 and diffusion MRI data obtained from 222 systemic glucocorticoid users, 557 inhaled glucocorticoid users compared to more than 24,000 control subjects.

The changes were greater in users of systemic steroids than in users of inhaled steroids, according to findings published in BMJ Open (link), which also suggested the effects might be even larger among long term users.

Using data from the UK Biobank, researchers looked for differences in in brain volume and structure using 22 volumetric and 14 diffusion imaging parameters between glucocorticoid users and controls, after excluding data based on neurological, psychiatric or endocrinological history, and use of psychotropic medication.

They found that for the primary outcome, both systemic and inhaled glucocorticoid use were associated with reduced white matter integrity (lower fractional anisotropy and higher mean diffusivity) compared with controls. Larger effect sizes were seen in systemic users than inhaled users.

Systemic use was also associated with larger caudate GMV, while inhaled users had smaller amygdala GMV than controls.

For secondary outcomes, systemic users performed worse on tests to assess complex processing speed (symbol digit substitution task) and reported more depressive symptoms, disinterest, tenseness/restlessness and tiredness/lethargy compared with controls. Inhaled users only reported more tiredness/lethargy.

Among people using chronic glucocorticoids there was a suggestion of a dose-dependent or duration-dependent effect of glucocorticoids on white matter microstructure, with smallest effect sizes in inhaled glucocorticoid users, larger effect sizes in systemic glucocorticoid users, and the largest effect sizes in chronic systemic glucocorticoid users.

The associations found might help to explain the neuropsychiatric effects, such as anxiety, depression, mania, and delirium frequently seen after long term use, said the researchers.

“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,” they wrote.

The study authors acknowledged 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 they were prescribed, since rheumatoid arthritis and COPD have also been associated with mental health impairment and reduced quality of life.

“Nevertheless, awareness for the potential of glucocorticoids to affect the brain and cause neuropsychiatric symptoms is important, since these medications are prescribed for a wide range of conditions by many different medical specialties and are used by a substantial proportion of the population,” they said.

“Moreover, further research into the underlying mechanisms, reversibility, and risk factors for development of neuropsychiatric side effects of glucocorticoids is warranted, ideally considering dose and duration of glucocorticoids, as well as single-nucleotide polymorphisms (SNPs) in the GR gene (NR3C1) that affect glucocorticoid sensitivity,” they concluded.

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