Systemic and local corticosteroid use is associated with reduced executive cognition, and mood and anxiety disorders
Open accessAbstract
BACKGROUND: Use of local corticosteroids, especially the inhaled types, has increasingly been associated with systemic uptake and consequent adverse effects. In this study, we assessed the associations between the use of different corticosteroid types with cognitive and neuropsychiatric adverse effects related to high glucocorticoid exposure. METHODS: In 83,592 adults (mean age 44 years, 59% women) of the general population (Lifelines Cohort Study), we analyzed the relationship between corticosteroid use with executive cognitive functioning (Ruff Figural Fluency Test), and presence of mood and anxiety disorders (Mini-International Neuropsychiatric Interview survey). We performed additional exploration for effects of physical quality of life (QoL; RAND-36), and inflammation (high-sensitive C-reactive protein [CRP]). RESULTS: Cognitive scores were lower among corticosteroid users, in particular of systemic and inhaled types, when compared to nonusers. Users of inhaled types showed lower cognitive scores irrespective of physical QoL, psychiatric disorders, and high-sensitive CRP. Overall corticosteroid use was also associated with higher likelihood for mood and anxiety disorders. Users of inhaled corticosteroids were more likely to have mood disorders (OR 1.40 [95% CI 1.19-1.65], p < 0.001) and anxiety disorders (OR 1.19 [95% CI 1.06-1.33], p = 0.002). These findings were independent of physical QoL. A higher likelihood for mood disorders was also found for systemic users whereas nasal and dermal corticosteroid users were more likely to have anxiety disorders. CONCLUSIONS: Commonly used local corticosteroids, in particular inhaled types, and systemic corticosteroids are associated with reduced executive cognitive functioning and a higher likelihood of mood and anxiety disorders in the general adult population.
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These relations between corticosteroid use and cardiometabolic sequelae seemed to be related to glucocorticoid receptor gene variants associated with increased or normal glucocorticoid sensitivity.
“These relations between corticosteroid use and cardiometabolic sequelae seemed to be related to glucocorticoid receptor gene variants that are associated with increased or normal glucocorticoid sensitivity.”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [38]
The Introduction (page unavailable) reports an association between corticosteroid use and adverse cardiometabolic outcomes. Neither that passage nor the Discussion's account of systemic effects links those outcomes to glucocorticoid receptor gene variants or to increased or normal glucocorticoid sensitivity; searches for those terms found no such passage. (LLM, conf=0.83)
Experimental — accuracy not yet measuredUse of local corticosteroids, particularly inhaled types, is associated with higher likelihood of metabolic syndrome, higher body mass index, reduced executive cognitive functioning, and higher likelihood of mood and anxiety disorders.
“In this light, it is of interest that we recently showed associations between use of local corticosteroids, particularly inhaled types, and higher likelihood of metabolic syndrome, higher body mass index, reduced executive cognitive functioning, and a higher likelihood of mood and anxiety disorders (37, 38).”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [38]
Several studies have highlighted deleterious effects of exogenous glucocorticoids on cognition.
“Several studies have highlighted the deleterious effects of these drugs on cognition (423–428).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [428]
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References 39 · Cited by 55
Research works printed but not linked: 3
- de Kloet ER, Oitzl MS, Joëls M. Functional im- plications of brain corticosteroid receptor di- versity. Cell Mol Neurobiol. 1993 Aug; 13(4): 433-55.
- McKlveen JM, Myers B, Herman JP. The me- dial prefrontal cortex: coordinator of auto- nomic, neuroendocrine and behavioural re- sponses to stress. J Neuroendocrinol. 2015 Jun; 27(6): 446-56.
- Daley-Yates PT. Inhaled corticosteroids: po- tency, dose equivalence and therapeutic in- dex. Br J Clin Pharmacol. 2015 Sep; 80(3): 372-80.
- Authors
- Savas, M., Vinkers, C. H., Rosmalen, J. G. M., Hartman, C. A., Wester, V. L., van den Akker, E. L. T., Iyer, A. M., McEwen, B. S., & van Rossum, E. F. C.
- Affiliations
- Erasmus MC (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- University Medical Center Groningen (NL)
- Rockefeller University (US)
- ORCID
- Venue
- Neuroendocrinology
- Publisher
- S. Karger AG
- Published
- 2019-06-21
- Volume
- 110
- Issue
- 3-4
- Pages
- 282-291
- ISSN
- 0028-3835 (ISSN-L)
- 1423-0194
- PMC
- PMC7114901
- OpenAlex
- W2950221897
- Cited by
- 55
- References
- 39
- Citations by year
- 2026: 10 · 2025: 8 · 2024: 6 · 2023: 8 · 2022: 14 · 2021: 8 · 2019: 1
- FWCI
- 4.66
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuroendocrinology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Pure Amsterdam UMC (submittedVersion, cc-by)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (91716453)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Keywords
- corticosteroid use, inhaled corticosteroids, systemic corticosteroids, executive function, cognitive decline, mood disorders, anxiety disorders, glucocorticoid exposure, quality of life, C-reactive protein, inflammation, intranasal corticosteroids
- MeSH terms
- Administration, Inhalation, Adrenal Cortex Hormones, Adult, Anxiety Disorders, Female, Humans, Male, Middle Aged, Cohort Studies, Mood Disorders, Executive Function, Cognitive Dysfunction
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