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
