Serum zonulin and claudin-5 levels in children with attention-deficit/hyperactivity disorder

Int J Psychiatry Clin Pract. 2021 Mar;25(1):49-55. doi: 10.1080/13651501.2020.1801754. Epub 2020 Aug 6.


Objective: This study aimed to investigate serum zonulin and claudin-5 levels of children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and healthy controls by controlling the parameters such as age, sex and body mass index (BMI) percentile which are known to affect these parameters.

Method: A total of 80 treatment-naive children and adolescents with ADHD and 40 healthy volunteer controls aged 8-12 years were enrolled in this study. The severities of ADHD symptoms were assessed via parent- and teacher-rated questionnaires. The severity of anxiety and depression symptoms of the children were assessed by the self-report inventories. Serum levels of zonulin and claudin-5 were measured using commercial enzyme-linked immunosorbent assay kits.

Results: The multivariate analysis of covariance (MANCOVA) revealed a significant main effect of groups in the serum zonulin and claudin-5 levels, an effect that was independent of age, sex and BMI percentile. Significant differences were found between the study groups in terms of serum log-claudin-5 levels. However, there was no significant difference between the study groups in terms of serum zonulin levels.

Conclusion: These findings provide additional evidence for dysregulation of the blood-brain barrier, especially abnormalities in claudin-5 function, which may be involved in the aetiology of ADHD.Key pointsADHD is one of the most common neurodevelopmental disorders of childhood. Although ADHD is quite common, its aetiology has yet to be fully explained.In recent years, studies on the relationship between intestinal and blood-brain brain barrier permeability and psychiatric disorders have increased.In our study, serum claudin-5 levels were higher in the ADHD group compared to the control group, while serum zonulin levels did not differ between the groups.

Keywords: Attention-deficit/hyperactivity disorder; blood–brain barrier; claudin-5; intestinal permeability; zonulin.

MeSH terms

  • Adolescent
  • Anxiety / blood*
  • Anxiety / etiology
  • Anxiety / physiopathology
  • Attention Deficit Disorder with Hyperactivity / blood*
  • Attention Deficit Disorder with Hyperactivity / physiopathology
  • Blood-Brain Barrier / physiopathology*
  • Child
  • Claudin-5 / blood*
  • Depression / blood*
  • Depression / etiology
  • Depression / physiopathology
  • Female
  • Haptoglobins
  • Humans
  • Intestines / physiopathology*
  • Male
  • Permeability
  • Protein Precursors / blood*


  • Claudin-5
  • Haptoglobins
  • Protein Precursors
  • zonulin