The use of prescribed steroids, including in inhalers, is linked to changes in the structure and volume of white and grey matter in the brain, suggests the findings of the largest study of its kind, published in the open access journal BMJ Open.
The associations found might help to
explain the neuropsychiatric effects, such as anxiety, depression, mania, and
delirium frequently seen after long term use, say the researchers.
Their immunosuppressive properties mean
that glucocorticoids, a class of synthetic steroids, are among some of the most
frequently prescribed drugs. They are used to treat a wide variety of medical
conditions.
The estimated annual population
prevalence in high income countries of systemic (infusions and tablets) medical
steroid use is thought to range between 0.5% and 3%.
While very effective, both systemic and
inhaled steroids are associated with many potentially serious metabolic,
cardiovascular, and musculoskeletal side effects, as well as neuropsychiatric
effects.
Previously published research suggests
that long term medical steroid use is associated with structural abnormalities
and shrinkage of certain areas of the brain. But most of these studies have
involved only small numbers of people with specific conditions.
And it’s still not clear if these
associations might also be observed in a broader sample of medical steroid
users, including those using inhaled steroids for respiratory conditions, such
as asthma.
In a bid to find out, the researchers
drew on data from the UK Biobank, comprising half a million 40–69 year olds
from the general population, to see if there were any detectable differences in
brain volume and structure between users and non-users of systemic and inhaled
steroids.
The researchers also wanted to know if
steroid use might be associated with differences in processing speed and
emotional responses.
The MRI brain scans of 222 people using
systemic steroids and 557 using inhaled steroids were compared with those of
24,106 non-users.
None of the study participants had
previously been diagnosed with neurological, psychiatric or hormonal
(endocrinological) disorders or was taking mood altering drugs, such as
antidepressants.
Participants filled in a questionnaire
to assess certain aspects of mood over the previous fortnight.
Comparison of the MRI scan results
showed that both systemic and inhaled steroid use was associated with less
intact white matter structure than was seen on the scans of those not on these
drugs. White matter has a role in neuronal connectivity and signalling in the
brain.
The effects were greater in systemic
users than in users of inhaled steroids. And further detailed analysis
suggested that the effects might be even larger among long term users.
Systemic use was associated with a
larger caudate compared with no use, while use of inhaled steroids was
associated with a smaller amygdala. Both the caudate and amygdala are grey
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 non-users, and they
reported significantly more depressive symptoms, apathy, restlessness and
fatigue/lethargy than non-users. Inhaled steroid users reported only more
tiredness/lethargy, and to a lesser degree than systemic steroid users.
“Although a causal relation between
glucocorticoid use and changes in the brain is likely based on the present and
previous studies, the cross-sectional nature of this study does not allow for
formal conclusions on causality,” caution the researchers.
They also point to certain limitations.
Only a few indicators of mood change were assessed, and only for the preceding
2 weeks; and the reported changes might have been related to the condition for
which steroids were prescribed rather than to steroid use itself.
Nor were the researchers able to
differentiate between steroid tablets and infusions for systemic users, all of
which may have influenced the findings.
But they write: “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 they conclude: “This study shows
that both systemic and inhaled glucocorticoids are associated with an
apparently widespread reduction in white matter integrity, which may in part
underlie the neuropsychiatric side effects observed in patients using
glucocorticoids.”
Given how widely used these drugs, both doctors and patients need to know about the possible effects on the brain, say the researchers, who now call for research into alternative treatment options.
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