Use of prescribed steroids, including in inhalers, is linked to changes in the structure and volume of white and gray matter in the brain, suggest results from the largest study of its kind, published in the free journal access BMJ open.
The associations found could help explain neuropsychiatric effects, such as anxiety, depression, mania and delirium commonly seen after long-term use, the researchers say.
Their immunosuppressive properties mean that glucocorticoids, a class of synthetic steroids, are among the most frequently prescribed medications. They are used to treat a wide variety of medical conditions.
The estimated annual prevalence in the population of high-income countries of systemic use of medical steroids (infusions and tablets) is thought to be between 0.5% and 3%.
Although highly effective, systemic and inhaled steroids are associated with numerous potentially serious metabolic, cardiovascular, and musculoskeletal side effects, as well as neuropsychiatric effects.
Previously published research suggests that long-term use of medical steroids is associated with structural abnormalities and shrinkage of certain areas of the brain. But most of these studies only involved a small number of people with specific conditions.
And it’s still unclear whether these associations could also be seen in a larger sample of medical steroid users, including those who use inhaled steroids for respiratory conditions, such as asthma.
In a bid to find out, the researchers relied on data from the UK Biobank, comprising half a million people aged 40 to 69 from the general population, to see if there were any detectable differences in the brain volume and structure between users and non-users. systemic and inhaled steroids.
The researchers also wanted to know if steroid use might be associated with differences in processing speed and emotional responses.
Brain MRIs of 222 people using systemic steroids and 557 using inhaled steroids were compared with those of 24,106 nonusers.
None of the study participants had previously been diagnosed with neurological, psychiatric, or hormonal (endocrinological) disorders or were taking psychotropic medications, such as antidepressants.
Participants completed a questionnaire to assess certain aspects of mood over the previous fortnight.
Comparison of MRI results showed that use of systemic and inhaled steroids was associated with less intact white matter structure than seen on CT scans of those not taking these drugs. White matter plays a role in neuronal connectivity and signaling in the brain.
Effects were greater in systemic users than in inhaled steroid users. And more detailed analysis suggested the effects could be even greater in long-term users.
Systemic use was associated with a larger caudate compared to no use, while inhaled steroid use was associated with a smaller amygdala. The caudate and amygdala are gray matter structures in the brain involved in cognitive and emotional processing.
Systemic steroid users also performed worse on a test designed to measure processing speed than nonusers, and they reported significantly more depressive symptoms, apathy, restlessness, and fatigue/lethargy. than non-users. Inhaled steroid users reported only more fatigue/lethargy, and to a lesser extent than systemic steroid users.
“Although a causal relationship between glucocorticoid use and changes in the brain is likely based on current and previous studies, the cross-sectional nature of this study does not allow formal conclusions about causation to be drawn,” warn the authors. researchers.
They also point out certain limits. Only a few mood change indicators were assessed, and only for the previous 2 weeks; and the reported changes may have been related to the condition for which the steroids were prescribed rather than the steroid use itself.
The researchers were also unable to differentiate between steroid tablets and infusions for systemic users, all of which may have influenced the results.
But they write: “Although it is unclear whether the observed effect sizes have any clinical implications for the population of glucocorticoid users as a whole, these results are remarkable given the common neuropsychiatric side effects of synthetic glucocorticoids. .”
And they conclude: “This study shows that systemic and inhaled glucocorticoids are associated with an apparently generalized reduction in white matter integrity, which may in part underlie the neuropsychiatric side effects observed in patients using glucocorticoids.”
Given the wide use of these drugs, doctors and patients need to be aware of the possible effects on the brain, say the researchers, who now call for research into alternative treatment options.
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Association between systemic and inhaled glucocorticoid use and changes in brain volume and white matter microstructure: a cross-sectional study using data from the UK Biobank, BMJ open (2022). DOI: 10.1136/bmjopen-2022-062446
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