Altered gray matter structure and white matter microstructure in patients with congenital adrenal hyperplasia: relevance for working memory performance
Abstract
Congenital adrenal hyperplasia (CAH) has been associated with brain structure alterations, but systematic studies are lacking. We explore brain morphology in 37 (21 female) CAH patients and 43 (26 female) healthy controls, aged 16-33 years, using structural magnetic resonance imaging to estimate cortical thickness, surface area, volume, subcortical volumes, and white matter (WM) microstructure. We also report data on a small cohort of patients (n = 8) with CAH, who received prenatal dexamethasone (DEX). Patients with CAH had reduced whole brain volume (4.23%) and altered structure of the prefrontal, parietal, and superior occipital cortex. Patients had reduced mean FA, and reduced RD and MD, but not after correcting for brain volume. The observed regions are hubs of the visuospatial working memory and default mode (DMN) networks. Thickness of the left superior parietal and middle frontal gyri was associated with visuospatial working memory performance, and patients with CAH performed worse on this task. Prenatal treatment with DEX affected brain structures in the parietal and occipital cortex, but studies in larger cohorts are needed. In conclusion, our study suggests that CAH is associated with brain structure alterations, especially in the working memory network, which might underlie the cognitive outcome observed in patients.
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White matter hyperintensities are found in patients with CAH, but are an uncommon finding in healthy adults aged <45 years.
“White matter hyperintensities are found in patients with CAH, but are an uncommon finding in healthy adults aged < 45 years (692,693).”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [693]
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Genome-wide investigation of DNA methylation in congenital adrenal hyperplasia
Karlsson, L., Barbaro, M., Ewing, E., Gómez-Cabrero, D., & Lajić, S. (2020) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2020.105699 · Cited by 4 · see citing works
Self-citationAltered regional gray matter in Congenital Adrenal Hyperplasia (CAH)
Eileen Luders, A., Spencer, D., Christian Gaser, B., Thankamony, A., Hughes, I. A., Srirangalingam, U., Gleeson, H. K., Hines, M., & Kurth, F. (2025) · Hormones and Behavior · doi:10.1016/j.yhbeh.2025.105766 · Cited by 4 · see citing works
Paparella, R., Panvino, F., Pucarelli, I., Niceta, M., Spaziani, M., Spalice, A., Pisani, F., Ardizzone, I., & Tarani, L. (2025) · European Journal of Pediatrics · doi:10.1007/s00431-025-06673-w · Cited by 3 · see citing works
Eileen Luders, A., Spencer, D., Christian Gaser, B., Thankamony, A., Hughes, I. A., Srirangalingam, U., Gleeson, H. K., Kung, K. T. F., Cabeen, R. P., Hines, M., et al. (2024) · Brain Communications · doi:10.1093/braincomms/fcae334 · Cited by 3 · see citing works
The corpus callosum in people with congenital adrenal hyperplasia (CAH)
Eileen Luders, A., Spencer, D., Dale, C. V., Hughes, I. A., Thankamony, A., Srirangalingam, U., Gleeson, H. K., Simpson, H., Hines, M., & Kurth, F. (2025) · Scientific Reports · doi:10.1038/s41598-025-88870-z · Cited by 3 · see citing works
Influence of gonadal steroids on cortical surface area in infancy
Alex, A. M., Ruvio, T., Xia, K., Jha, S. C., Girault, J. B., Wang, L., Li, G., Shen, D. G., Cornea, E. A., Styner, M. A., et al. (2021) · Cerebral Cortex · doi:10.1093/cercor/bhab410 · Cited by 3 · see citing works
Messina, V., Westeinde, A. V., Padilla, N., & Lajić, S. (2022) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgac426 · Cited by 3 · see citing works
Self-citationPsychoendocrinology of congenital adrenal hyperplasia
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Brain activity during visuospatial working memory in congenital adrenal hyperplasia
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Lind‐Holst, M., Hansen, D., Main, K. M., Juul, A., Andersen, M., Dunø, M., Rasmussen, Å. K., Jørgensen, N., Gravholt, C. H., & Berglund, A. (2024) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgae780 · Cited by 2 · see citing works
A Case of Prenatally Diagnosed Congenital Adrenal Hyperplasia With Brain Morphometric Differences
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Effects of Congenital Adrenal Hyperplasia (CAH) and Biological Sex on Brain Size
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Congenital Adrenal Hyperplasia in the Adolescent
Kim, M. S., Liang, M. C., Kokorowski, P. K., Tseng, T., Koppin, C. M., & Geffner, M. E. (2022) · Springer eBooks · doi:10.1007/978-3-319-17002-2_59-2
Kim, M. S., Pickering, T. A., Cotter, D. L., Fraga, N. R., Luo, S., Won, C., Geffner, M. E., & Herting, M. M. (2024) · Hormone Research in Paediatrics · doi:10.1159/000537847
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Eileen Luders, A., Spencer, D., Hughes, I. A., Thankamony, A., Srirangalingam, U., Gleeson, H. K., Hines, M., & Kurth, F. (2026) · Scientific Reports · doi:10.1038/s41598-026-45407-2
Verde, V., Wörther, H., Kühle, A., Grunwald, P., Tschaidse, L., Chojnacki, M., Ilmberger, S., Berente, S., Reisch, N., & Krämer, U. M. (2026) · Hormones and Behavior · doi:10.1016/j.yhbeh.2026.105953
Hippocampal volume and white matter impairments in patients with congenital adrenal hyperplasia
Savoia, A., Kancsar, D., Nordenström, A., Westeinde, A. V., & Lajić, S. (2026) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgag312
Self-citation
- Authors
- van’t Westeinde, A., Karlsson, L., Thomsen Sandberg, M., Nordenström, A., Padilla, N., & Lajic, S.
- Affiliations
- Department of Women’s and Children’s Health, Pediatric Endocrinology Unit, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
- Karolinska University Hospital (SE)
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-12-10
- Volume
- 30
- Issue
- 5
- Pages
- 2777-2788
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- OpenAlex
- W2996377728
- Cited by
- 37
- References
- 77
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 6 · 2023: 6 · 2022: 11 · 2021: 6 · 2020: 2
- FWCI
- 1.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Cerebral Cortex (publishedVersion)
- PubMed (publishedVersion)
- Funders
- International Fund raising for Congenital Adrenal Hyperplasia
- European Society for Pediatric Endocrinology
- Stockholm County Council
- Foundation of Lisa and Johan Grönberg
- Stiftelsen Frimurare Barnhuset i Stockholm
- Samaritan Foundation
- Jerringfonden Foundation
- Foundation for Research and Education in Pediatric Endocrinology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Keywords
- congenital adrenal hyperplasia, gray matter structure, white matter microstructure, working memory, visuospatial working memory, cortical thickness, brain volume, default mode network, prenatal dexamethasone, prefrontal cortex, parietal cortex, occipital cortex, cortical surface area
- MeSH terms
- Adolescent, Adrenal Hyperplasia, Congenital, Adult, Cognition, Female, Humans, Magnetic Resonance Imaging, Male, Memory, Short-Term, Psychomotor Performance, Cohort Studies, Young Adult, White Matter, Gray Matter
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