Total brain, cortical, and white matter volumes in children previously treated with glucocorticoids

Abstract

BackgroundPerinatal exposure to glucocorticoids and elevated endogenous glucocorticoid levels during childhood can have detrimental effects on the developing brain. Here, we examined the impact of glucocorticoid treatment during childhood on brain volumes.MethodsA total of 30 children and adolescents with rheumatic or nephrotic disease previously treated with glucocorticoids and 30 controls matched on age, sex, and parent education underwent magnetic resonance imaging (MRI) of the brain. Total cortical gray and white matter, brain, intracranial volume, and total cortical thickness and surface area were derived from MRI scans.ResultsPatients had significantly smaller gray and white matter and total brain volumes relative to healthy controls. Brain volume differences disappeared when accounting for intracranial volume, as patients had relatively smaller intracranial volumes. Group differences were mainly driven by the children with rheumatic disease. Total cortical thickness and cortical surface area did not significantly differ between groups. We found no significant associations between glucocorticoid-treatment variables and volumetric measures.ConclusionObserved smaller total brain, cortical gray, and white matter volumes in children and adolescents previously treated with glucocorticoids compared with that in healthy controls may reflect both developmental and degenerative processes. Prospective longitudinal studies are warranted to clarify whether findings are related to treatment or disease.

Previous glucocorticoid treatment in childhood and adolescence is associated with long-term differences in subcortical grey matter volume and microstructure

“…We included these two different extra-cerebral pediatric diseases with the aim to control for potential disease-related effects. In previous work, we observed that these patients had lower verbal intellectual abilities (Holm et al, 2015) and smaller total brain volumes as compared to healthy controls (Holm et al, 2018). Furthermore, the children treated with glucocorticoid showed sex-dependent differences in endogenous cortisol profiles compared to healthy controls, with girls having higher cortisol awakening response (CAR) and boys having higher cortisol levels during the day (Vestergaard et al, 2017).…”

“…The participants in the present study are the same as in our recent study investigating the effects on glucocorticoid treatment on global structural brain measures (Holm et al, 2018). Therefore, if identical, information on participants, clinical characteristics and background variables is presented between quotation marks followed by the reference to the previous article.…”

“…The controls were between 7.0 and 15.6 years of age and consisted of 11 boys and 19 girls. The subjects were part of a larger cohort, which has been described in detail elsewhere (Holm et al, 2018). Of the initial thirty-eight included patients, seven did not complete MRI scanning and one was excluded because of poor image quality due to motion artefacts.…”

“…The study was ethically approved by the Scientific Ethical Committee, Capital Region, Denmark (H-KF-01- 131/03 and addendum of June 2009). Written informed consent was obtained from parents of all participants” (Holm et al, 2018). The study was conducted in accordance with the Helsinki declaration.…”

“…“Patients' medical charts were reviewed, and diagnosis and glucocorticoid treatment data were collected” (Holm et al, 2018). “The study included 11 patients with nephrotic syndrome and 19 with rheumatic disease.…”