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

IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM
Mimi S Kim, Trevor A Pickering, Devyn L Cotter, Nicole R Fraga, Shan Luo, Cindy Y Won, Mitchell E Geffner, Megan M Herting
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引用次数: 0

Abstract

Introduction: Patients with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency 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±3.4y, 16 females) and 35 controls (13.0±2.8y, 20 females) 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 <0.05) indicating axonal disorganization, reduced myelin content, and/or higher microglial density within the affected white matter tracts. For the full cohort, SF was correlated with MCP-1 (r=-0.41), visceral adipose tissue (r=-0.25), and waist-to-height ratio (r=-0.27, all p's <0.05); ST was correlated with MCP-1 (r=0.31) and TNF-α (r= 0.29, all p's <0.05); however, after adjusting for CAH status, almost all correlations were attenuated for significance.

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.

先天性肾上腺皮质增生症儿童和青少年肥胖和炎症的神经相关性。
简介由于 21- 羟化酶缺乏而导致的典型先天性肾上腺皮质增生症(CAH)患者从孩提时代起就表现出肥胖,包括中心性肥胖和炎症。此外,CAH患者的大脑表型也受到影响,皮质-边缘灰质体积减少,白质异常。方法:27 名 CAH(12.6±3.4 岁,16 名女性)和 35 名对照组(13.0±2.8 岁,20 名女性)对灰质相关区域[前额叶皮质 (PFC)、杏仁核、海马]和白质微结构[穹窿、终纹 (ST)]进行 MRI 检查。此外,还进行了人体测量和实验室分析。Relaimpo分析(线性回归的相对重要性;方差百分比)确定了各组之间差异最大的大脑结构。随后的回归进一步量化了这些关系的程度和方向。相关性分析了CAH状态下大脑结构、肥胖和炎症之间的关系:在灰质方面,CAH患者与对照组的前额叶(PFC)(方差为13.3%)及其上额叶(SF)亚区(14%)差异最大;在白质方面,ST(16%)差异最大。CAH患者的尾中额[β = -0.56, (-0.96, -0.15)]和上额[β = -0.58 (-0.92, -0.25)]亚区体积较小,穹窿的定向弥散指数增加[β = 0.56 (0.01, 1.10)] 和 ST [β = 0.85 (0.34, 1.36)],穹窿[β = -0.91 (-1.42, -0.42)]和 ST [β = -0.83 (-1.34, -0.33)]的分数各向异性降低(所有 P 均为结论):CAH儿科患者的主要脑结构、身体成分和炎症标志物之间的关系可能在很大程度上是由CAH引起的,这对这一高危人群的肥胖和神经炎症有影响。
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来源期刊
Hormone Research in Paediatrics
Hormone Research in Paediatrics ENDOCRINOLOGY & METABOLISM-PEDIATRICS
CiteScore
4.90
自引率
6.20%
发文量
88
审稿时长
4-8 weeks
期刊介绍: The mission of ''Hormone Research in Paediatrics'' is to improve the care of children with endocrine disorders by promoting basic and clinical knowledge. The journal facilitates the dissemination of information through original papers, mini reviews, clinical guidelines and papers on novel insights from clinical practice. Periodic editorials from outstanding paediatric endocrinologists address the main published novelties by critically reviewing the major strengths and weaknesses of the studies.
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