Working memory performance is reduced in children with congenital adrenal hyperplasia
Open accessAbstract
Individuals with classic congenital adrenal hyperplasia (CAH) experience impaired glucocorticoid production and are treated postnatally with glucocorticoids. Prior research with animals and other human populations indicates that glucocorticoids can influence memory, particularly working memory. We tested the hypothesis that children with CAH would show reduced working memory. Children in the United Kingdom, aged 7-11years, with classical CAH (31 girls, 26 boys) were compared to their unaffected relatives (30 girls, 20 boys) on a test of working memory, the Digit Span test. Vocabulary was also assessed to measure verbal intelligence for control purposes. Children with CAH showed reduced working memory performance compared to controls, on both components of the Digit Span test: p=.008 for Digit Span Forward, and p=.027 for Digit Span Backward, and on a composite score, p=.004. These differences were of moderate size (d=.53 to .70). Similar differences were also seen in a subset of 23 matched pairs of children with CAH and their relatives (d=.78 to .92). There were no group differences on Vocabulary. Glucocorticoid abnormality, including treatment effects, could be responsible for the reduced Digit Span performance in children with CAH. Other factors related to CAH, such as salt-wasting crises, could also be involved. Additional research is needed to identify the cause of the memory reduction, which will help to determine if more rapid diagnosis or more precise glucocorticoid treatment would help prevent memory reduction. Educational interventions might also be considered for children with CAH.
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Systematic review and meta-analysis did not detect significant differences in behavior or temperament depending on prenatal Dex exposure.
“Systematic review and meta-analysis of several studies did not detect significant differences in behavior or temperament depending on prenatal Dex exposure (103, 137, 138).”
From Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society* Clinical Practice Guideline (2018) · cites this paper as [137]
Individuals with CAH who were not prenatally exposed to Dex may have reduced working memory or short-term memory.
“individuals with CAH who were not prenatally exposed to Dex may have reduced working memory or short-term memory (137, 138).”
From Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society* Clinical Practice Guideline (2018) · cites this paper as [137]
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Hampson, E. (2015) · Laterality Asymmetries of Body Brain and Cognition · doi:10.1080/1357650x.2015.1102924 · Cited by 7 · see citing works
Park, J., Das, U., Didi, M., Ramakrishnan, R., Peak, M., Newland, P., & Blair, J. (2018) · Pediatric Drugs · doi:10.1007/s40272-018-0306-0 · Cited by 6 · see citing works
Memory in female adolescents with congenital adrenal hyperplasia due to 21-hydroxylase deficiency
Reyes, T. M. E., Martín, D. C., Álvarez, M. Á., & Falhammar, H. (2024) · Endocrine · doi:10.1007/s12020-024-03806-3 · Cited by 5 · see citing works
Changes in resting-state functional connectivity in patients with congenital adrenal hyperplasia
Messina, V., Westeinde, A. V., Padilla, N., & Lajić, S. (2022) · NeuroImage Clinical · doi:10.1016/j.nicl.2022.103081 · Cited by 5 · see citing works
Neufeld, S., Collaer, M. L., Spencer, D., Pasterski, V., Hindmarsh, P. C., Hughes, I. A., Acerini, C. L., & Hines, M. (2023) · Hormones and Behavior · doi:10.1016/j.yhbeh.2023.105310 · Cited by 5 · see citing works
Self-citationHypothalamic–Pituitary–Adrenal Axis: Congenital Adrenal Hyperplasia
Pasterski, V., & Hughes, I. A. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-803592-4.00070-5 · Cited by 5 · see citing works
Self-citationGenome-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
Omary, A., Khalifeh, N., Cotter, D. L., Kim, M. S., Choudhury, F., Ahmadi, H., Geffner, M. E., & Herting, M. M. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad158 · Cited by 4 · see citing works
Psychoendocrinology of congenital adrenal hyperplasia
Meyer‐Bahlburg, H. F. L. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-821424-4.00027-7 · Cited by 2 · see citing works
Pulungan, A. B., Puteri, H. A., Waladhiyaputri, V., Chandra, A. P., Ratnasari, A. F., Idaayen, F., Fadiana, G., Armstrong, K. E., & Utari, A. (2025) · Clinical Pediatric Endocrinology · doi:10.1297/cpe.2024-0051 · Cited by 2 · see citing works
Brain activity during visuospatial working memory in congenital adrenal hyperplasia
Westeinde, A. V., Zimmermann, M., Messina, V., Karlsson, L., Padilla, N., & Lajić, S. (2022) · Cortex · doi:10.1016/j.cortex.2022.10.012 · Cited by 2 · see citing works
Genetic Defects of Female Sexual Differentiation
Cools, M., der Grinten, H. L. C., Baere, E. D., Callens, N., & Dessens, A. B. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-803592-4.00068-7 · Cited by 1 · see citing works
Steroid Replacement in Adrenal Insufficiency
Blair, J., Debono, M., & Ross, R. J. M. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.64307-6 · Cited by 1 · see citing works
Antenatal glucocorticosteroids treatment: mechanisms of child healths programming
Владимировна, Ш. А., & Суплотова, Л. А. (2022) · Meditsinskiy sovet = Medical Council · doi:10.21518/2079-701x-2022-16-10-110-114
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
Steroid replacement in adrenal insufficiency
Blair, J., Debono, M., & Ross, R. J. M. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-13825-6.00147-3
Nokoff, N., Fechner, P. Y., Kim, M. S., Marshall, I. H., Merke, D. P., Sarafoglou, K., Hartzell, A. L., Lin, V. H., & Thornton, P. (2026) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgag192
Polito, N. D., Gambarota, F., Hampson, E., & Herlitz, A. (2026) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2026.106877
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
- Authors
- Browne, W. V., Hindmarsh, P. C., Pasterski, V., Hughes, I. A., Acerini, C. L., Spencer, D., Neufeld, S., & Hines, M.
- Affiliations
- University of Cambridge (GB)
- University College London (GB)
- Corresponding author
- Hines, Melissa
- ORCID
- Venue
- Hormones and Behavior
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 67
- Pages
- 83-88
- ISSN
- 0018-506X (ISSN-L)
- PMC
- PMC4332548
- OpenAlex
- W2062283084
- Cited by
- 54
- References
- 61
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 2 · 2020: 8 · 2019: 3 · 2018: 8 · 2017: 4 · 2016: 8 · 2015: 2
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hormones and Behavior (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (R01HD024542)
- 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
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- congenital adrenal hyperplasia, working memory, glucocorticoids, digit span, short-term memory, children, glucocorticoid therapy, salt-wasting crisis, general intelligence, numeracy
- MeSH terms
- Adrenal Hyperplasia, Congenital, Child, Female, Humans, Male, Memory, Short-Term
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