Serum zonulin and claudin-5 levels in children with obsessive–compulsive disorder

Işık, Ümit; Avşar, Pınar Aydoğan; Aktepe, Evrim; Doğuç, Duygu Kumbul; Kılıç, Faruk; Büyükbayram, Halil İbrahim

doi:10.1080/08039488.2020.1715474

Cited by 23 publications

(28 citation statements)

References 43 publications

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“…For the pre-specified objective for this systematic review, there were five studies eligible, i.e., five case-control studies [ 5 , 6 , 7 , 8 , 9 ], with all patients diagnosed with mental disorders, compared to healthy controls and with the majority of recruited participants being males. The full characteristics of the included studies are shown in Table 3 .…”

Section: Resultsmentioning

confidence: 99%

“…The full characteristics of the included studies are shown in Table 3 . One of the five studies included investigated the association between intestinal barrier function, immune response, and ADHD [ 5 ]; three investigated the association between impaired IP, immune responses, and serum zonulin/plasma haptoglobin levels and ASD [ 6 , 7 , 8 ]; and one investigated serum zonulin and claudin-5 levels in OCD [ 9 ].…”

Section: Resultsmentioning

confidence: 99%

“…The interplay between mental disorders, IP, and the intestinal microbiota has become a rapidly growing area of research. Increased IP has been examined with regard to emotional, behavioral, and neurodevelopmental disorders such as ADHD, ASD, major depressive disorders (MDD), obsessive–compulsive disorder (OCD), and schizophrenia [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, a similar permeability mechanism related to the CNS and the blood–brain barrier has been described [ 11 ]. Claudin-5, a transmembrane tight-junction protein, is expressed in the blood–brain barrier and plays a crucial role in maintaining the integrity of the brain endothelial barrier, and changes in this function may contribute to enhanced permeability of the endothelial barrier of the brain [ 9 , 11 ]. Increased expression of claudin-5 has been associated with mental disorders.…”

Section: Introductionmentioning

confidence: 99%

“…Increased expression of claudin-5 has been associated with mental disorders. Serum claudin-5 levels have been found significantly higher in OCD subjects [ 9 ]. Furthermore, an aberrant pattern of claudin-5 immunoreactivity has been observed in schizophrenia subjects [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Zonulin-Dependent Intestinal Permeability in Children Diagnosed with Mental Disorders: A Systematic Review and Meta-Analysis

et al. 2020

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Worldwide, up to 20% of children and adolescents experience mental disorders, which are the leading cause of disability in young people. Research shows that serum zonulin levels are associated with increased intestinal permeability (IP), affecting neural, hormonal, and immunological pathways. This systematic review and meta-analysis aimed to summarize evidence from observational studies on IP in children diagnosed with mental disorders. The review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search of the Cochrane Library, PsycINFO, PubMed, and the Web of Science identified 833 records. Only non-intervention (i.e., observational) studies in children (<18 years) diagnosed with mental disorders, including a relevant marker of intestinal permeability, were included. Five studies were selected, with the risk of bias assessed according to the Newcastle–Ottawa scale (NOS). Four articles were identified as strong and one as moderate, representing altogether 402 participants providing evidence on IP in children diagnosed with attention deficit and hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive–compulsive disorder (OCD). In ADHD, elevated serum zonulin levels were associated with impaired social functioning compared to controls. Children with ASD may be predisposed to impair intestinal barrier function, which may contribute to their symptoms and clinical outcome compared to controls. Children with ASD, who experience gastro-intestinal (GI) symptoms, seem to have an imbalance in their immune response. However, in children with OCD, serum zonulin levels were not significantly different compared to controls, but serum claudin-5, a transmembrane tight-junction protein, was significantly higher. A meta-analysis of mean zonulin plasma levels of patients and control groups revealed a significant difference between groups (p = 0.001), including the four studies evaluating the full spectrum of the zonulin peptide family. Therefore, further studies are required to better understand the complex role of barrier function, i.e., intestinal and blood–brain barrier, and of inflammation, to the pathophysiology in mental and neurodevelopmental disorders. This review was PROSPERO preregistered, (162208).

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