Is there a link between peripheral inflammation and blood brain barrier integrity in children with attention-deficit/hyperactivity disorder? A case-control study

Abstract Background Claudin-5 is a vital constituent of tight junctions, which are critical elements of the blood-brain barrier. In people with neuropsychiatric disorders, peripheral inflammation is often found, although it is less common in healthy populations. The objective of this study was to ex...

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Main Authors: Samira Zien Sayed, Zienab Osama Hassan, Wedad M. Abdelraheem, Rasha Samir Refaat, Ibtehal Saad Abuelela
Format: Article
Language:English
Published: BMC 2024-11-01
Series:BMC Pediatrics
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Online Access:https://doi.org/10.1186/s12887-024-05254-4
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author Samira Zien Sayed
Zienab Osama Hassan
Wedad M. Abdelraheem
Rasha Samir Refaat
Ibtehal Saad Abuelela
author_facet Samira Zien Sayed
Zienab Osama Hassan
Wedad M. Abdelraheem
Rasha Samir Refaat
Ibtehal Saad Abuelela
author_sort Samira Zien Sayed
collection DOAJ
description Abstract Background Claudin-5 is a vital constituent of tight junctions, which are critical elements of the blood-brain barrier. In people with neuropsychiatric disorders, peripheral inflammation is often found, although it is less common in healthy populations. The objective of this study was to examine the relationship between Claudin-5, peripheral immune cells, and the severity of symptoms in children with attention deficit hyperactivity disorder (ADHD). Methods The study included a cohort of 33 children diagnosed with ADHD and 29 control subjects, all aged between 5 and 12 years. The intensity of ADHD symptoms was evaluated using Conner’s questionnaire, which the parents completed. Each kid had serum level measurements of Claudin-5 and a complete blood count in order to establish a correlation with symptoms of ADHD. Results Serum Claudin-5 levels are lower in the ADHD group compared to the control group; median (IQR) = 30.94 (4-137) and 44.12 (4–223.3) respectively (p = 0.69). The levels of neutrophils and neutrophil/lymphocyte ratio are significantly higher in ADHD than in controls (p = 0.011 and 0.015, respectively). Lymphocytes have a significant positive correlation with ADHD symptoms severity, namely, total Conner’s scale and inattention (p = 0.021 and 0.004 respectively), while NLR has a significant negative correlation with total Conner’s score and impulsivity (p = 0.046, p = 0.038), also a negative correlation yet not significant between serum Claudin-5 level and total Conner’s score, hyperactivity, impulsivity, and inattention. Neutrophils were found to have a significant positive linear regression with Claudin-5 (p = 0.023). Conclusion These results revealed that BBB integrity is affected in ADHD children, as claudin-5 levels were found to be lower in children with ADHD, lymphocytes were found to be associated with increased ADHD symptoms severity, and NLR was associated with decreased symptoms severity, which may be via the positive effects of increased neutrophils on Claudin-5 levels.
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spelling doaj-art-d2b0f5ab8b5347b79055fcb7091970aa2025-08-20T02:38:33ZengBMCBMC Pediatrics1471-24312024-11-012411910.1186/s12887-024-05254-4Is there a link between peripheral inflammation and blood brain barrier integrity in children with attention-deficit/hyperactivity disorder? A case-control studySamira Zien Sayed0Zienab Osama Hassan1Wedad M. Abdelraheem2Rasha Samir Refaat3Ibtehal Saad Abuelela4Department of Pediatrics, Faculty of Medicine, Minia UniversityDepartment of Pediatrics, Faculty of Medicine, Minia UniversityDepartment of Medical Microbiology and Immunology, Faculty of Medicine, Minia UniversityDepartment of Neuropsychiatry, Faculty of Medicine, Minia UniversityDepartment of Pediatrics, Faculty of Medicine, Minia UniversityAbstract Background Claudin-5 is a vital constituent of tight junctions, which are critical elements of the blood-brain barrier. In people with neuropsychiatric disorders, peripheral inflammation is often found, although it is less common in healthy populations. The objective of this study was to examine the relationship between Claudin-5, peripheral immune cells, and the severity of symptoms in children with attention deficit hyperactivity disorder (ADHD). Methods The study included a cohort of 33 children diagnosed with ADHD and 29 control subjects, all aged between 5 and 12 years. The intensity of ADHD symptoms was evaluated using Conner’s questionnaire, which the parents completed. Each kid had serum level measurements of Claudin-5 and a complete blood count in order to establish a correlation with symptoms of ADHD. Results Serum Claudin-5 levels are lower in the ADHD group compared to the control group; median (IQR) = 30.94 (4-137) and 44.12 (4–223.3) respectively (p = 0.69). The levels of neutrophils and neutrophil/lymphocyte ratio are significantly higher in ADHD than in controls (p = 0.011 and 0.015, respectively). Lymphocytes have a significant positive correlation with ADHD symptoms severity, namely, total Conner’s scale and inattention (p = 0.021 and 0.004 respectively), while NLR has a significant negative correlation with total Conner’s score and impulsivity (p = 0.046, p = 0.038), also a negative correlation yet not significant between serum Claudin-5 level and total Conner’s score, hyperactivity, impulsivity, and inattention. Neutrophils were found to have a significant positive linear regression with Claudin-5 (p = 0.023). Conclusion These results revealed that BBB integrity is affected in ADHD children, as claudin-5 levels were found to be lower in children with ADHD, lymphocytes were found to be associated with increased ADHD symptoms severity, and NLR was associated with decreased symptoms severity, which may be via the positive effects of increased neutrophils on Claudin-5 levels.https://doi.org/10.1186/s12887-024-05254-4ADHDBlood brain barrierClaudin-5Peripheral inflammationNeutrophil/lymphocyte ratio and children
spellingShingle Samira Zien Sayed
Zienab Osama Hassan
Wedad M. Abdelraheem
Rasha Samir Refaat
Ibtehal Saad Abuelela
Is there a link between peripheral inflammation and blood brain barrier integrity in children with attention-deficit/hyperactivity disorder? A case-control study
BMC Pediatrics
ADHD
Blood brain barrier
Claudin-5
Peripheral inflammation
Neutrophil/lymphocyte ratio and children
title Is there a link between peripheral inflammation and blood brain barrier integrity in children with attention-deficit/hyperactivity disorder? A case-control study
title_full Is there a link between peripheral inflammation and blood brain barrier integrity in children with attention-deficit/hyperactivity disorder? A case-control study
title_fullStr Is there a link between peripheral inflammation and blood brain barrier integrity in children with attention-deficit/hyperactivity disorder? A case-control study
title_full_unstemmed Is there a link between peripheral inflammation and blood brain barrier integrity in children with attention-deficit/hyperactivity disorder? A case-control study
title_short Is there a link between peripheral inflammation and blood brain barrier integrity in children with attention-deficit/hyperactivity disorder? A case-control study
title_sort is there a link between peripheral inflammation and blood brain barrier integrity in children with attention deficit hyperactivity disorder a case control study
topic ADHD
Blood brain barrier
Claudin-5
Peripheral inflammation
Neutrophil/lymphocyte ratio and children
url https://doi.org/10.1186/s12887-024-05254-4
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