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.