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Brain Differences in the Prefrontal Cortex, Amygdala, and Hippocampus in Youth with Congenital Adrenal Hyperplasia

Herting, Megan M. and Azad, Anisa and Kim, Robert and Tyszka, J. Michael and Geffner, Mitchell E. and Kim, Mimi S. (2020) Brain Differences in the Prefrontal Cortex, Amygdala, and Hippocampus in Youth with Congenital Adrenal Hyperplasia. Journal of Clinical Endocrinology and Metabolism, 105 (4). Art. No. dgaa023. ISSN 0021-972X. PMCID PMC7058446 . doi:10.1210/clinem/dgaa023.

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Context: Classical Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency results in hormone imbalances present both prenatally and postnatally that may impact the developing brain. Objective: To characterize gray matter morphology in the prefrontal cortex and subregion volumes of the amygdala and hippocampus in youth with CAH, compared to controls. Design: A cross-sectional study of 27 CAH youth (16 female; 12.6 ± 3.4 year) and 35 typically developing, healthy controls (20 female; 13.0 ± 2.8 year) with 3-T magnetic resonance imaging scans. Brain volumes of interest included bilateral prefrontal cortex, and nine amygdala and six hippocampal subregions. Between-subject effects of group (CAH vs control) and sex, and their interaction (group-by-sex) on brain volumes were studied, while controlling for intracranial volume (ICV) and group differences in body mass index and bone age. Results: CAH youth had smaller ICV and increased cerebrospinal fluid volume compared to controls. In fully-adjusted models, CAH youth had smaller bilateral, superior and caudal middle frontal volumes, and smaller left lateral orbito-frontal volumes compared to controls. Medial temporal lobe analyses revealed the left hippocampus was smaller in fully-adjusted models. CAH youth also had significantly smaller lateral nucleus of the amygdala and hippocampal subiculum and CA1 subregions. Conclusions: This study replicates previous findings of smaller medial temporal lobe volumes in CAH patients, and suggests that lateral nucleus of the amygdala, as well as subiculum and subfield CA1 of the hippocampus are particularly affected within the medial temporal lobes in CAH youth.

Item Type:Article
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URLURL TypeDescription CentralArticle
Tyszka, J. Michael0000-0001-9342-9014
Additional Information:© 2020 Endocrine Society. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model ( Received: 15 October 2019; Published: 17 January 2020. The authors gratefully thank all participants and their families. In addition, we would like to acknowledge Norma Martinez, Heather Ross, Christina Koppin, Kimberly Felix, Veeraya Tanawattanacharoen, and Eva Gabor for assisting with participant recruitment and data collection. Finally, we thank CARES Foundation for their ongoing support of the CHLA CAH Comprehensive Care Center. This study was supported by National Institutes of Health K01 MH1087610 (MMH), R03HD090308 (MMH), and K23HD084735 (MSK), CARES Foundation (MEG and MSK), and the Abell Foundation (MEG). Disclosure Summary: MEG receives grant support from Novo Nordisk; consultant fees from Daiichi Sankyo, Ferring, Novo Nordisk, Nutrition & Growth Solutions, Pfizer, Sandoz, and Spruce Biosciences; serves on data safety monitoring boards for Ascendis, Millendo, and Tolmar; and receives royalties from McGraw-Hill and UpToDate. Data Availability Statement: Restrictions apply to the availability of data generated or analyzed during this study to preserve patient confidentiality or because they were used under license. The corresponding author will on request detail the restrictions and any conditions under which access to some data may be provided.
Funding AgencyGrant Number
NIHK01 MH1087610
Abell FoundationUNSPECIFIED
Subject Keywords:amygdala, hippocampus, neurodevelopment, structural MRI, Congenital Adrenal Hyperplasia, pediatrics
Issue or Number:4
PubMed Central ID:PMC7058446
Record Number:CaltechAUTHORS:20200122-110053771
Persistent URL:
Official Citation:Megan M Herting, Anisa Azad, Robert Kim, J Michael Tyszka, Mitchell E Geffner, Mimi S Kim, Brain Differences in the Prefrontal Cortex, Amygdala, and Hippocampus in Youth with Congenital Adrenal Hyperplasia, The Journal of Clinical Endocrinology & Metabolism, Volume 105, Issue 4, April 2020, dgaa023,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:100835
Deposited By: Tony Diaz
Deposited On:23 Jan 2020 00:06
Last Modified:16 Nov 2021 17:57

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