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Brain Differences in the Prefrontal Cortex, Amygdala, and Hippocampus in Youth with Congenital Adrenal Hyperplasia
Megan M Herting1,2,3, Anisa Azad1, Robert Kim1
1Department of Preventive Medicine, Keck School of Medicine of University of Southern California, Los Angeles, California.
Insights
Youth with congenital adrenal hyperplasia (CAH) show altered brain development, with smaller prefrontal cortex and medial temporal lobe volumes, including the amygdala and hippocampus. These findings highlight neuroanatomical differences in individuals with CAH.
Area of Science:
- Neuroendocrinology
- Developmental Neuroscience
- Neuroimaging
Background:
- Classical congenital adrenal hyperplasia (CAH) is caused by 21-hydroxylase deficiency, leading to hormonal imbalances that can affect brain development.
- Prenatal and postnatal hormonal disruptions in CAH may impact neuroanatomical structures crucial for cognitive and emotional processing.
Purpose of the Study:
- To investigate gray matter morphology in the prefrontal cortex and specific subregions of the amygdala and hippocampus in youth with CAH compared to healthy controls.
- To identify potential sex-specific differences in brain morphology within the CAH cohort.
Main Methods:
- A cross-sectional study involving 27 youth with CAH and 35 typically developing controls, aged 12-13 years.
- 3-Tesla magnetic resonance imaging (MRI) was used to assess brain volumes, focusing on the prefrontal cortex, amygdala, and hippocampus subregions.
- Statistical analyses controlled for intracranial volume (ICV), body mass index (BMI), and bone age to isolate group and sex effects.
Main Results:
- Youth with CAH exhibited smaller intracranial volumes (ICV) and increased cerebrospinal fluid (CSF) volume compared to controls.
- CAH youth demonstrated reduced volumes in bilateral superior and caudal middle frontal cortex, and left lateral orbitofrontal cortex.
- Significant reductions were observed in the left hippocampus, the lateral nucleus of the amygdala, and hippocampal subfields CA1 and subiculum in CAH youth.
Conclusions:
- This study confirms previous findings of reduced medial temporal lobe volumes in CAH patients.
- Specific medial temporal lobe structures, including the lateral amygdala nucleus, hippocampal subiculum, and CA1 subfield, are particularly affected in youth with CAH.
- The observed neuroanatomical differences underscore the impact of hormonal imbalances in CAH on brain structure development.
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.
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