Neural Correlates of Obesity and Inflammation in Children and Adolescents with Congenital Adrenal Hyperplasia

Abstract

Introduction: Patients with classical congenital adrenal hyperplasia (CAH) exhibit an increased prevalence of obesity from childhood including central adiposity and inflammation. There is also an emerging affected brain phenotype in CAH, with decreased cortico-limbic gray matter volumes and white matter abnormalities. We aimed to study the relationship between brain structure, obesity, and inflammation in children and adolescents with CAH compared to controls. Methods: 27 CAH (12.6 ± 3.4 y, 16 females) and 35 control (13.0 ± 2.8 y, 20 females) participants had MRI of gray matter regions of interest (prefrontal cortex [PFC], amygdala, hippocampus) and white matter microstructure (fornix, stria terminalis [ST]). Anthropometric measures and lab analytes were obtained. Relaimpo analyses (relative importance for linear regression; percent variance) identified which brain structures were most different between groups. Subsequent regressions further quantified the magnitude and direction of these relationships. Correlations analyzed relationships between brain structure, obesity, and inflammation in the context of CAH status. Results: PFC (13.3% variance) and its superior frontal (SF) subregion (14%) were most different between CAH and controls for gray matter; ST (16%) for white matter. Patients with CAH had lower caudal middle frontal (β = −0.56 [−0.96, −0.15]) and superior frontal (β = −0.58 [−0.92, −0.25]) subregion volumes, increased orientation dispersion index in the fornix (β = 0.56 [0.01, 1.10]) and ST (β = 0.85 [0.34, 1.36]), and decreased fractional anisotropy in the fornix (β = −0.91 [−1.42, −0.42]) and ST (β = −0.83 [−1.34, −0.33]) (all p’s r = −0.41), visceral adipose tissue (r = −0.25), and waist-to-height ratio (r = −0.27, all p’s r = 0.31) and TNF-α (r = 0.29, all p’s Conclusions: Relationships among key brain structures, body composition, and inflammatory markers in pediatric patients with CAH could be largely driven by having CAH, with implications for obesity and neuroinflammation in this high-risk population.