Altered Gray Matter Structure and White Matter Microstructure in Patients with Congenital Adrenal Hyperplasia: Relevance for Working Memory Performance.

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.

Sex-Dimorphic Effects of Prenatal Treatment With Dexamethasone.

CONTEXT: Dexamethasone (DEX) is used to prevent virilization in female fetuses at risk of congenital adrenal hyperplasia (CAH). Given that treatment has to be started before the genotype is known, 7 out of 8 fetuses will be exposed to DEX without benefit. OBJECTIVE: To evaluate long-term cognitive effects of prenatal DEX therapy in healthy (non-CAH) DEX-treated children. DESIGN AND SETTING: Observational study with patient and control groups from a single research institute. PARTICIPANTS: Healthy (non-CAH) DEX-treated subjects (n = 34) and untreated population controls (n = 66) from Sweden, aged 7-17 years. INTERVENTION: DEX-treatment used in unborn children at risk of CAH, during first trimester of fetal life. MAIN OUTCOME MEASURES: Standardized neuropsychological tests and questionnaires were used. RESULTS: DEX treatment has widespread negative effects in girls. In Wechsler Intelligence Scales for Children-III scale subtests, we observed significant interactions between DEX and GENDER (coding, P = .044; block design, P = .013; vocabulary, P = .025) and a trend for the subtest digit span (P = .074). All interactions were driven by DEX effects in girls, but not boys, with DEX-treated females showing lower scores than female untreated controls (coding, P = .068, d = 0.66; block design, P = .021, d = 0.81; vocabulary, P = .014, d = 0.84; digit span, P = .001, d = 1.0). Likewise, DEX-treated girls tend to have poorer visual spatial working memory performance than controls (span board test forward: P = .065, d = .80). We observed no effects on long-term memory, handedness, speed of processing, nor self-perceived or parentally reported scholastic performance. CONCLUSIONS: Early prenatal DEX exposure affects cognitive functions in healthy girls, ie, children who do not benefit from the treatment. It can therefore not be considered safe to use this therapy in the context of CAH.