Increased zonulin is associated with hyperactivity and social dysfunctions in children with attention deficit hyperactivity disorder

Compr Psychiatry. 2018 Nov;87:138-142. doi: 10.1016/j.comppsych.2018.10.006. Epub 2018 Oct 29.


Background: In attention deficit hyperactivity disorder (ADHD), deteriorations of brain gut axis has been shown in previous studies. One area where the most important challenges are seen in ADHD is social functioning. Zonulin is a protein found in the intestinal intraepithelial component; it has been shown that the level of zonulin increases when intestinal permeability is impaired. Changes in intestinal function were shown in ADHD. Zonulin has been shown to be associated with social impairment in children with autism spectrum disorder. In this study, it was aimed to evaluate the relationship between the ADHD symptoms and zonulin in children with ADHD. Secondarily relation of zonulin and difficulties in social functioning was examined in these children.

Methods: Forty children diagnosed with ADHD and forty-one healthy children similar age and gender to ADHD group and their mothers were included in the study. Children without any chronic systemic immunological or infectious diseases were included in the case and control group. The ADHD symptoms were scored by the DuPaul ADHD scale and the social functioning of the children was assessed by the Social Responsiveness Scale (SRS). Serum zonulin levels were analyzed by enzyme-linked immunosorbent assay.

Results: Children with ADHD had higher serum zonulin levels and were more impaired in social functioning compared to controls. The level of zonulin was independently predicted with hyperactivity symptoms and SRS scores in regression analysis.

Conclusion: In this sample of children with ADHD, elevated zonulin levels were associated with increased symptoms of hyperactivity and impairment of social functioning.

Publication types

  • Evaluation Study

MeSH terms

  • Adolescent
  • Attention Deficit Disorder with Hyperactivity / blood*
  • Attention Deficit Disorder with Hyperactivity / complications
  • Attention Deficit Disorder with Hyperactivity / psychology
  • Biomarkers / blood
  • Case-Control Studies
  • Child
  • Cholera Toxin / blood*
  • Female
  • Haptoglobins
  • Humans
  • Male
  • Mothers
  • Protein Precursors
  • Social Behavior
  • Social Behavior Disorders / blood*
  • Social Behavior Disorders / psychology


  • Biomarkers
  • Haptoglobins
  • Protein Precursors
  • zonulin
  • Cholera Toxin