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Is there a link between peripheral inflammation and blood brain barrier integrity in children with
Samira Zien Sayed1, Zienab Osama Hassan1, Wedad M Abdelraheem2
1Department of Pediatrics, Faculty of Medicine, Minia University, El-Minia, Egypt.
Insights
Children with ADHD show lower Claudin-5 levels, indicating altered blood-brain barrier integrity. Increased lymphocytes correlate with ADHD symptom severity, while neutrophils may positively impact Claudin-5 levels.
Area of Science:
- Neuroscience
- Immunology
- Pediatrics
Background:
- Claudin-5 is a key component of the blood-brain barrier (BBB), essential for its integrity.
- Peripheral inflammation is frequently observed in neuropsychiatric disorders, including ADHD.
- Investigating Claudin-5 and immune cell relationships in ADHD offers insights into BBB dysfunction.
Purpose of the Study:
- To examine the association between Claudin-5 levels, peripheral immune cell counts, and ADHD symptom severity in children.
- To determine if BBB integrity is compromised in children diagnosed with ADHD.
- To explore potential correlations between immune markers and clinical presentation in pediatric ADHD.
Main Methods:
- A cohort of 33 children with ADHD and 29 controls (ages 5-12) were recruited.
- ADHD symptom severity was assessed using parental Conner's questionnaires.
- Serum Claudin-5 levels and complete blood counts were analyzed for correlations with ADHD symptoms.
Main Results:
- Children with ADHD exhibited lower serum Claudin-5 levels compared to controls.
- Significantly higher neutrophil and neutrophil-to-lymphocyte ratio (NLR) were observed in the ADHD group.
- Lymphocytes positively correlated with ADHD symptom severity (total score, inattention), while NLR showed a negative correlation.
Conclusions:
- ADHD in children is associated with compromised BBB integrity, evidenced by reduced Claudin-5 levels.
- Lymphocyte levels correlate with increased ADHD symptom severity.
- Elevated neutrophils may enhance Claudin-5 levels, potentially influencing BBB integrity and symptom severity in ADHD.
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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