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

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Mimi S KimChildren's Hospital Los Angeles, Center for Endocrinology, Diabetes and Metabolism, Los Angeles, California, USA.

Trevor A PickeringDepartment of Population and Public Health Sciences, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.

Devyn L CotterDepartment of Population and Public Health Sciences, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.

Nicole R FragaChildren's Hospital Los Angeles, Center for Endocrinology, Diabetes and Metabolism, Los Angeles, California, USA.

Shan LuoDepartment of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.

Cindy Y WonChildren's Hospital Los Angeles, Center for Endocrinology, Diabetes and Metabolism, Los Angeles, California, USA.

Mitchell E GeffnerChildren's Hospital Los Angeles, Center for Endocrinology, Diabetes and Metabolism, Los Angeles, California, USA.

Megan M HertingDepartment of Population and Public Health Sciences, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.

Funding

Southern California Clinical and Translational Science InstituteUL1TR001855 · NCATS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Thomas A Buchanan, Michele D. Kipke · 2016 to 2026

$81.3M

Southern California Clinical and Translational Science InstituteUL1TR000130 · NCATS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BUCHANAN, THOMAS A · 2012 to 2015

$36.0M

Brain and Adipose Contributors to Food Seeking in Youth with Adrenal HyperplasiaK23HD084735 · NICHD · CHILDREN'S HOSPITAL OF LOS ANGELES · PI KIM, MIMI SUSAN · 2016 to 2018

$474k

Effects of Androgen Excess on Lipid Distribution in Congenital Adrenal HyperplasiaR03HD101718 · NICHD · CHILDREN'S HOSPITAL OF LOS ANGELES · PI KIM, MIMI SUSAN · 2020 to 2021

$183k

The Role of Androgens in Amygdala Subnuclei Development Across Human AdolescenceR03HD090308 · NICHD · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HERTING, MEGAN MARIE · 2017 to 2018

$179k

NCATS NIH HHS UL1 TR000130NCATS NIH HHS UL1 TR001855NICHD NIH HHS K23 HD084735NICHD NIH HHS R03 HD090308NICHD NIH HHS R03 HD101718

6 · The paper itself

Abstract

introductionPatients 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.

methods27 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.

resultsPFC (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.

conclusionsRelationships 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.

introductionPatients 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.

methods27 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.

resultsPFC (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.

conclusionsRelationships 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.

Indexed as

Adrenal Hyperplasia, CongenitalGray MatterInflammationObesityPediatric ObesityWhite MatterAdolescentChildFemaleHumansMagnetic Resonance ImagingMalePrefrontal Cortex21-hydroxylase deficiencyCongenital adrenal hyperplasiaNeurodevelopmentObesityPediatricsStructural MRIWhite matter