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 Microstructural Differences in Youth with Classical Congenital Adrenal Hyperplasia

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab520 ◽

2021 ◽

Author(s):

Devyn L Cotter ◽

Anisa Azad ◽

Ryan P Cabeen ◽

Mimi S Kim ◽

Mitchell E Geffner ◽

...

Keyword(s):

White Matter ◽

Congenital Adrenal Hyperplasia ◽

Stria Terminalis ◽

Adrenal Hyperplasia ◽

Hydroxylase Deficiency ◽

Brain White Matter ◽

White Matter Microstructure ◽

Subcortical Regions ◽

21 Hydroxylase Deficiency ◽

Microstructural Integrity

Abstract Context Gray matter morphology in the prefrontal cortex and subcortical regions, including the hippocampus and amygdala, are affected in youth with classical congenital adrenal hyperplasia (CAH). It remains unclear if white matter connecting these aforementioned brain regions is compromised in youth with CAH. Objective To examine brain white matter microstructure in youth with CAH compared to controls. Design A cross-sectional sample of 23 youths with CAH due to 21-hydroxylase deficiency (12.9±3.5 year; 61% female) and 33 healthy controls (13.1±2.8 year; 61% female) with 3T multi-shell diffusion-weighted magnetic resonance brain scans. Main Outcome Measures Complementary modeling approaches, including diffusion tensor imaging (DTI) and Neurite Orientation Dispersion and Density Imaging (NODDI), to examine in vivo white matter microstructure in six white matter tracts that innervate the prefrontal and subcortical regions. Results DTI showed CAH youth had lower fractional anisotropy in both the fornix and stria terminalis, and higher mean diffusivity in the fornix compared to controls. NODDI modeling revealed that CAH youth have a significantly higher orientation dispersion index in the stria terminalis compared to controls. Decreases in white matter microstructural integrity were associated with smaller hippocampal and amygdala volumes in CAH youth. Conclusions These patterns of microstructure reflect less restricted water diffusion likely due to less coherency in oriented microstructure. These results suggest that white matter microstructural integrity in the fornix and stria terminalis is compromised and may be an additional related brain phenotype alongside affected hippocampus and amygdala neurocircuitry in individuals with CAH.

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Nicotine Effects on White Matter Microstructure in Young Adults

Archives of Clinical Neuropsychology ◽

10.1093/arclin/acy101 ◽

2019 ◽

Vol 35 (1) ◽

pp. 10-21 ◽

Cited By ~ 2

Author(s):

Megan M Kangiser ◽

Alicia M Thomas ◽

Christine M Kaiver ◽

Krista M Lisdahl

Keyword(s):

Working Memory ◽

Young Adults ◽

White Matter ◽

Fractional Anisotropy ◽

Sustained Attention ◽

Verbal Memory ◽

Diffusion Tensor ◽

Memory Performance ◽

Mean Diffusivity ◽

White Matter Microstructure

Abstract Objective Nicotine use is widely prevalent among youth, and is associated with white matter microstructural changes as measured by diffusion tensor imaging (DTI). In adults, nicotine use is generally associated with lower fractional anisotropy (FA), but in adolescents/young adults (≤30 years), microstructure appears healthier, indicated by higher FA. This cross-sectional study examined associations between nicotine use and white matter microstructure using fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in young adults. Methods Fifty-three participants (18 nicotine users [10 female]/35 controls [17 female]) ages 18–25 underwent MRI scan, neuropsychological battery, toxicology screening, and drug use interview. Nicotine group associations with FA and MD were examined in various white matter tracts. In significant tracts, AD and RD were measured. Exploratory correlations were conducted between significant tracts and verbal memory and sustained attention/working memory performance. Results Nicotine users exhibited significantly lower FA than controls in the left anterior thalamic radiation, left inferior longitudinal fasciculus, left superior longitudinal fasciculus—temporal, and left uncinate fasciculus. In these tracts, AD and RD did not differ, nor did MD differ in any tract. White matter quality was positively correlated with sustained attention/working memory performance. Conclusions Cigarette smoking may disrupt white matter microstructure. These results are consistent with adult studies, but inconsistent with adolescent/young adult studies, likely due to methodological and sample age differences. Further studies should examine longitudinal effects of nicotine use on white matter microstructure in a larger sample.

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Working memory performance is reduced in children with congenital adrenal hyperplasia

Hormones and Behavior ◽

10.1016/j.yhbeh.2014.11.014 ◽

2015 ◽

Vol 67 ◽

pp. 83-88 ◽

Cited By ~ 30

Author(s):

Wendy V. Browne ◽

Peter C. Hindmarsh ◽

Vickie Pasterski ◽

Ieuan A. Hughes ◽

Carlo L. Acerini ◽

...

Keyword(s):

Working Memory ◽

Congenital Adrenal Hyperplasia ◽

Memory Performance ◽

Adrenal Hyperplasia

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Quantitative Brain MRI in Congenital Adrenal Hyperplasia: In Vivo Assessment of the Cognitive and Structural Impact of Steroid Hormones

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2017-01481 ◽

2017 ◽

Vol 103 (4) ◽

pp. 1330-1341 ◽

Cited By ~ 12

Author(s):

Emma A Webb ◽

Lucy Elliott ◽

Dominic Carlin ◽

Martin Wilson ◽

Kirsty Hall ◽

...

Keyword(s):

White Matter ◽

Magnetic Resonance ◽

Congenital Adrenal Hyperplasia ◽

Brain Morphology ◽

Resonance Spectroscopy ◽

Adrenal Hyperplasia ◽

Hydroxylase Deficiency ◽

Brain White Matter ◽

White Matter Microstructure ◽

21 Hydroxylase Deficiency

Abstract Context Brain white matter hyperintensities are seen on routine clinical imaging in 46% of adults with congenital adrenal hyperplasia (CAH). The extent and functional relevance of these abnormalities have not been studied with quantitative magnetic resonance imaging (MRI) analysis. Objective To examine white matter microstructure, neural volumes, and central nervous system (CNS) metabolites in CAH due to 21-hydroxylase deficiency (21OHD) and to determine whether identified abnormalities are associated with cognition, glucocorticoid, and androgen exposure. Design, Setting, and Participants A cross-sectional study at a tertiary hospital including 19 women (18 to 50 years) with 21OHD and 19 age-matched healthy women. Main Outcome Measure Recruits underwent cognitive assessment and brain imaging, including diffusion weighted imaging of white matter, T1-weighted volumetry, and magnetic resonance spectroscopy for neural metabolites. We evaluated white matter microstructure by using tract-based spatial statistics. We compared cognitive scores, neural volumes, and metabolites between groups and relationships between glucocorticoid exposure, MRI, and neurologic outcomes. Results Patients with 21OHD had widespread reductions in white matter structural integrity, reduced volumes of right hippocampus, bilateral thalami, cerebellum, and brainstem, and reduced mesial temporal lobe total choline content. Working memory, processing speed, and digit span and matrix reasoning scores were reduced in patients with 21OHD, despite similar education and intelligence to controls. Patients with 21OHD exposed to higher glucocorticoid doses had greater abnormalities in white matter microstructure and cognitive performance. Conclusion We demonstrate that 21OHD and current glucocorticoid replacement regimens have a profound impact on brain morphology and function. If reversible, these CNS markers are a potential target for treatment.

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