先天性肾上腺皮质增生症儿童及青少年肥胖与炎症的神经关联
Neural Correlates of Obesity and Inflammation in Children and Adolescents with Congenital Adrenal Hyperplasia.
作者信息
Kim Mimi S, Pickering Trevor A, Cotter Devyn L, Fraga Nicole R, Luo Shan, Won Cindy Y, Geffner Mitchell E, Herting Megan M
机构信息
Children's Hospital Los Angeles, Center for Endocrinology, Diabetes and Metabolism, Los Angeles, California, USA.
The Saban Research Institute at Children's Hospital Los Angeles, Los Angeles, California, USA.
出版信息
Horm Res Paediatr. 2025;98(2):174-184. doi: 10.1159/000537847. Epub 2024 Feb 19.
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 < 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.
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 < 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.
引言
经典型先天性肾上腺皮质增生症（CAH）患者从儿童期起肥胖患病率就有所增加，包括中心性肥胖和炎症。CAH患者还出现了一种新的脑部受累表型，即皮质-边缘灰质体积减少和白质异常。我们旨在研究与对照组相比，CAH儿童和青少年的脑结构、肥胖和炎症之间的关系。
方法
27名CAH患者（年龄12.6±3.4岁，女性16名）和35名对照者（年龄13.0±2.8岁，女性20名）接受了感兴趣灰质区域（前额叶皮质[PFC]、杏仁核、海马体）和白质微结构（穹窿、终纹[ST]）的MRI检查。获取了人体测量指标和实验室分析物。Relaimpo分析（线性回归的相对重要性；方差百分比）确定了两组之间差异最大的脑结构。随后的回归进一步量化了这些关系的大小和方向。相关性分析了在CAH状态背景下脑结构、肥胖和炎症之间的关系。
结果
对于灰质，CAH组和对照组之间差异最大的是PFC（方差13.3%）及其额上（SF）亚区域（14%）；对于白质，是ST（16%）。CAH患者的额中回尾侧（β=-0.56[-0.96，-0.15]）和额上回（β=-0.58[-0.92，-0.25]）亚区域体积较小，穹窿（β=0.56[0.01，1.10]）和ST（β=0.85[0.34，1.36]）的方向离散指数增加，穹窿（β=-0.91[-1.42，-0.42]）和ST（β=-0.83[-1.34，-0.33]）的各向异性分数降低（所有p值<0.05），表明受影响的白质束内轴突紊乱、髓鞘含量减少和/或小胶质细胞密度较高。对于整个队列，SF与单核细胞趋化蛋白-1（MCP-1）（r=-0.41）、内脏脂肪组织（r=-（此处重复了部分内容，可删除多余部分）
结论
CAH儿科患者关键脑结构、身体成分和炎症标志物之间的关系可能很大程度上是由患有CAH所驱动的，这对这一高危人群的肥胖和神经炎症具有影响。
引言
经典型先天性肾上腺皮质增生症（CAH）患者从儿童期起肥胖患病率就有所增加，包括中心性肥胖和炎症。CAH患者还出现了一种新的脑部受累表型，即皮质-边缘灰质体积减少和白质异常。我们旨在研究与对照组相比，CAH儿童和青少年的脑结构、肥胖和炎症之间的关系。
方法
27名CAH患者（年龄12.6±3.4岁，女性16名）和35名对照者（年龄13.0±2.8岁，女性20名）接受了感兴趣灰质区域（前额叶皮质[PFC]、杏仁核、海马体）和白质微结构（穹窿、终纹[ST]）的MRI检查。获取了人体测量指标和实验室分析物。Relaimpo分析（线性回归的相对重要性；方差百分比）确定了两组之间差异最大的脑结构。随后的回归进一步量化了这些关系的大小和方向。相关性分析了在CAH状态背景下脑结构、肥胖和炎症之间的关系。
结果
对于灰质，CAH组和对照组之间差异最大的是PFC（方差13.3%）及其额上（SF）亚区域（14%）；对于白质，是ST（16%）。CAH患者的额中回尾侧（β=-0.（此处文本不完整，可补充完整）
完整译文
引言
经典型先天性肾上腺皮质增生症（CAH）患者从儿童期起肥胖患病率就有所增加，包括中心性肥胖和炎症。CAH患者还出现了一种新的脑部受累表型，即皮质-边缘灰质体积减少和白质异常。我们旨在研究与对照组相比，CAH儿童和青少年的脑结构、肥胖和炎症之间的关系。
方法
27名CAH患者（年龄12.6±3.4岁，女性16名）和35名对照者（年龄13.0±2.8岁，女性20名）接受了感兴趣灰质区域（前额叶皮质[PFC]、杏仁核、海马体）和白质微结构（穹窿、终纹[ST]）的MRI检查。获取了人体测量指标和实验室分析物。Relaimpo分析（线性回归的相对重要性；方差百分比）确定了两组之间差异最大的脑结构。随后的回归进一步量化了这些关系的大小和方向。相关性分析了在CAH状态背景下脑结构、肥胖和炎症之间的关系。
结果
对于灰质，CAH组和对照组之间差异最大的是PFC（方差13.3%）及其额上（SF）亚区域（14%）；对于白质，是ST（16%）。CAH患者的额中回尾侧（β=-0.56[-0.96, -0.15]）和额上回（β=-0.58[-0.92, -0.25]）亚区域体积较小，穹窿（β=0.56[0.01, 1.1]）和ST（β=0.85[0.34, 1.36]）的方向离散指数增加，穹窿（β=-0.91[-1.42, -0.42]）和ST（β=-0.83[-1.34, -0.33]）的各向异性分数降低（所有p值<0.05），表明受影响的白质束内轴突紊乱、髓鞘含量减少和/或小胶质细胞密度较高。对于整个队列，SF与单核细胞趋化蛋白-1（MCP-1）（r=-0.41）、内脏脂肪组织（r=-0.25）和腰高比（r=-0.27，所有p值<0.05）相关；ST与MCP-1（r=0.31）和肿瘤坏死因子-α（r=0.29，所有p值<0.05）相关；然而，在调整CAH状态后，几乎所有相关性的显著性都减弱了。
结论
CAH儿科患者关键脑结构、身体成分和炎症标志物之间的关系可能很大程度上是由患有CAH所驱动的，这对这一高危人群的肥胖和神经炎症具有影响。
Zotero 插件