Article - The Association between ADHD and Celiac Disease in Children.

Plain Language Summary

Untreated coeliac disease (CeD) can be accompanied by an array of neurological symptoms. Some of these symptoms are similar to those observed in attention deficit hyperactive disorder (ADHD), like an inability to focus, lack of mental alertness, physical under-activity and clinically measurable under-activity in particular brain regions. The mechanism of such symptoms is not fully understood but is thought to be linked to low-grade inflammation in the brain as a result of permeability in the gut and blood-brain barrier, which could contribute to the presentation of ADHD-like symptoms. CeD can persist for many years in seemingly healthy people (silent CeD) without gut symptoms. In this period, ADHD-like symptoms are particularly common and may be treatment resistant if not accompanied by a gluten-free diet Since 2015, there have been several studies showing an association between CeD and ADHD. This is an updated systematic review including 23 studies of children and young adults, which found an association between ADHD and CeD, in contrast to previous reviews that found no clear association. This review paid particular attention to the diagnostic criteria of ADHD and its subtypes, highlighting the need to examine the subtypes of ADHD in future studies. Specifically, the inattentive subtype may be a behavioural ADHD phenotype that could respond to a gluten-free diet. The authors advocate screening ADHD patients for CeD and encourage the consideration of non-neurological symptoms in the assessment of ADHD to identify potential CeD cases.

Expert Review

Reviewer: Kate Lawrence

7th Aug 2023

Conflict of interest

None

Take home message

There is an association between celiac disease (CeD) and attention deficit hyperactive disorder (ADHD).
Some children with ADHD may respond well to gluten-free diet.

Evidence category

B: Systematic reviews including RCTs of limited number

Summary review

This systematic review explored the association between coeliac disease (CeD) and attention deficit hyperactive disorder (ADHD).

Methods

The review was conducted following the PRISMA reporting guidelines. Inclusion criteria for the search:

Search terms of ADHD and CeD
Participants < 18 years.

52 papers were retrieved and screened 23 met inclusion/exclusion criteria

Results

13 studies (out of the 23) demonstrated an association between ADHD and CeD
Most studies reporting a positive association were published post 2015
The largest study reported (112,240 patients with CeD) demonstrates that ADHD showed an association of OR = 1.75 in in CeD.
The study was limited by several factors including study design of the studies included in the review, which were mostly observational and some without control.

The author declares no conflict of interest.

Clinical practice applications

Evidence from across the literature suggests that children with untreated or newly diagnosed CeD may find that following a gluten-free diet can help improve some symptoms associated with ADHD
The author suggests that there may be a behavioural phenotype of ADHD that responds to a gluten-free diet. If this is the case, it suggests that screening of ADHD patients for celiac disease may be important.

Considerations for future research

The number of studies were relatively small and varied in design. Further large-scale studies would help further inform the understanding of the association and potential therapeutic benefits of gluten-free diet.
It would be interesting to further explore how different subtypes of ADHD, especially the inattentive subtype, may be associated with CeD.
In particular, it might be useful to consider how the clinical construct of sluggish cognitive tempo (SCT) is associated, since SCT symptoms overlap with the neurological manifestations of CeD.

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Abstract

[{"label":"UNLABELLED","text":"Controversy around the association between celiac disease (CeD) and attention deficit hyperactive disorder (ADHD) was addressed by a systematic review in 2015, ultimately showing no association. Since 2015, there have been several studies showing an association between celiac disease and attention deficit hyperactive disorder. This is an updated systematic review."},{"label":"BACKGROUND","text":"Most experts agree on the recommendation to not screen as part of the standard of care for ADHD in persons with CeD or vice versa. Simultaneously, they propose that untreated patients with CeD and neurological symptoms such as chronic fatigue, inattention, pain, and headache could be predisposed to ADHD-like behavior, namely inattention (which may be alleviated by following a gluten-free diet). The inattentive subtype of ADHD that encompasses the symptoms of inattention is phenotypically heterogeneous, as it includes the clinical construct of sluggish cognitive tempo (SCT). SCT symptoms overlap with the neurological manifestations of CeD."},{"label":"METHODS","text":"A systematic search (PRISMA) of PubMed, Google Scholar, EMBASE, Web of Science, Stanford Lane, SCOPUS, and Ovid was conducted for articles up to 21 February 2022. Of these, 23 studies met the criteria."},{"label":"RESULTS","text":"Out of the 23 studies, 13 showed a positive association between ADHD and CeD. Most studies that showed a positive association had been published in the last five years. Inconsistencies in the results remain due to the heterogeneous methodology used, specifically for ADHD and the outcome questionnaires, as well as a lack of reporting on ADHD subtypes."},{"label":"CONCLUSION","text":"There is an association between ADHD and celiac disease. The current methodological limitations will be lessened if we examine the subtypes of ADHD."}]