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

Abstract

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 as compared to controls. Design A cross-sectional study of 27 CAH youth (16 female; 12.6 ± 3.4 years) and 35 typically developing, healthy controls (20 female; 13.0 ± 2.8 years) with 3-T magnetic resonance imaging scans. Brain volumes of interest included bilateral prefrontal cortex and 9 amygdala and 6 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 Congenital adrenal hyperplasia 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 orbitofrontal volumes compared to controls. Medial temporal lobe analyses revealed that the left hippocampus was smaller in fully-adjusted models. Congenital adrenal hyperplasia 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 the 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.

The Success of a Screening Program Is Largely Dependent on Close Collaboration between the Laboratory and the Clinical Follow-Up of the Patients

“…Patients were treated either with hydrocortisone, prednisolone, or dexamethasone. Also here, reductions in the volumes of the prefrontal cortex, amygdala, and hippocampus were observed [ 48 ].…”

“…More recent observational studies from the UK, USA, and Sweden regarding brain morphology in patients with CAH have revealed that patients show reductions in cortical and limbic regions of the brain that are important for the working memory [ 45 , 47 , 48 ]. This new evidence points to the fact that alterations in brain structure and possibly also in the functional organization of the brain may underlie the cognitive changes [ 45 , 47 , 48 ]. In the UK study [ 45 ], patients with CAH showed reductions in volumes of the right hippocampus, left amygdala, bilateral thalamus, cerebellum, and brainstem.…”

“…The American cohort [ 48 ] comprised children (age range 8–18 years) and analyzed the MRI data with a focus on the prefrontal cortex and regions of the hippocampus and the amygdala. The patients almost exclusively had SW CAH and approximately half of the cohort was diagnosed through neonatal screening.…”

Restructuring of amygdala subregion apportion across adolescence

“…Details of the in vivo amygdala probabilistic atlas construction, validation, estimates of individual differences, and comparison with previous atlas’ have been previously reported ( Tyszka and Pauli, 2016 ; Pauli et al, 2018 ). As previously published ( Herting et al, 2020 ), we adapted this technique to allow for each youth’s image to be registered to the CIT168 atlas using a B-spline bivariate symmetric normalization (SyN) diffeomorphic registration algorithm from ANTs version 2.2 ( Avants et al, 2007 ). Applying the inverse diffeomorphism mapped the CIT168 probabilistic atlas labels to the individual space of each participant, yielding probabilistic ROIs for left and right total amygdala and the following nine subregions: lateral nucleus (LA); dorsal and intermediate divisions of the basolateral nucleus (BLDI); ventral division of the basolateral nucleus and paralaminar nucleus (BLVPL); basomedial nucleus (BM); central nucleus (CEN); cortical and medial nuclei (CMN); amygdala transition areas (ATA); amygdalostriatal transition area (ASTA); and anterior amygdala area (AAA).…”

No Evidence for a Difference in 2D:4D Ratio between Youth with Elevated Prenatal Androgen Exposure due to Congenital Adrenal Hyperplasia and Controls

“…Serial radiographs of the left hand and wrist were obtained for bone age assessment as part of standard care in youth with CAH, and as part of an evaluation of short stature in otherwise healthy control youth. A smaller proportion of CAH and control participants had x-rays obtained as part of different research studies (Kim et al, 2015;Herting et al, 2020).…”