Reduced cortical thickness in individuals with congenital adrenal hyperplasia (CAH)

Congenital adrenal hyperplasia (CAH), a genetic condition that disrupts cortisol synthesis, is associated with elevated androgen levels in females with CAH. Altered hormonal milieus have been linked to changes in brain structure, yet little is known about how CAH affects the cerebral cortex. Here, we investigated vertex-wise cortical thickness in 53 individuals with CAH (33 women and 20 men) and 53 sex- and age-matched controls (33 women and 20 men) using surface-based morphometry. There were no significant effects of biological sex and no significant diagnosis-by-sex interaction. However, there was a significant effect of diagnosis, with thinner cortices in various regions across the left and right lateral and medial surfaces in individuals with CAH compared to controls. These findings point to widespread cortical alterations in CAH, independent of sex, and extend prior evidence of structural brain variations in this endocrine disorder. The observed cortical thinning may result from multiple factors, including prenatally reduced cortisol levels, potential long-term consequences of postnatal glucocorticoid treatment, and ongoing physiological and psychosocial stressors.

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Publication Details

Journal
Scientific Reports
Published
2026-03-24
DOI
https://doi.org/10.1038/s41598-026-45407-2
Primary Topic
Sexual Differentiation and Disorders
Type
article
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article

Reduced cortical thickness in individuals with congenital adrenal hyperplasia (CAH)

Scientific Reports
Sexual Differentiation and Disorders
article

Reduced cortical thickness in individuals with congenital adrenal hyperplasia (CAH)

article en

Abstract

Congenital adrenal hyperplasia (CAH), a genetic condition that disrupts cortisol synthesis, is associated with elevated androgen levels in females with CAH. Altered hormonal milieus have been linked to changes in brain structure, yet little is known about how CAH affects the cerebral cortex. Here, we investigated vertex-wise cortical thickness in 53 individuals with CAH (33 women and 20 men) and 53 sex- and age-matched controls (33 women and 20 men) using surface-based morphometry. There were no significant effects of biological sex and no significant diagnosis-by-sex interaction. However, there was a significant effect of diagnosis, with thinner cortices in various regions across the left and right lateral and medial surfaces in individuals with CAH compared to controls. These findings point to widespread cortical alterations in CAH, independent of sex, and extend prior evidence of structural brain variations in this endocrine disorder. The observed cortical thinning may result from multiple factors, including prenatally reduced cortisol levels, potential long-term consequences of postnatal glucocorticoid treatment, and ongoing physiological and psychosocial stressors.

Scientific ReportsVol. 16(1)
Ikerbasque (ES), University of Southern California (US), Uppsala University (SE), University College Hospital (GB), Universidad de Deusto (ES), University of Auckland (NZ), University of Cambridge (GB), Queen Elizabeth Hospital Birmingham (GB), Auckland University of Technology (NZ), Jena University Hospital (DE), Addenbrooke's Hospital (GB), University College London (GB)
Good health and well-being
Openalex Percentile: Top 11%
Sexual Differentiation and Disorders
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Reduced cortical thickness in individuals with congenital adrenal hyperplasia (CAH) · Scientific Reports (2026) | TGRS Research Map | TGRS