Attention deficit hyperactivity disorder and gastrointestinal morbidity in a large cohort of young adults

Kedem, Sivan; Yust‐Katz, Shlomit; Carter, Dan; Levi, Zohar; Kedem, Ron; Dickstein, Adi; Daher, Salah; Katz, Lior H.

doi:10.3748/wjg.v26.i42.6626

Cited by 17 publications

(15 citation statements)

References 35 publications

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“…existence of clusters of shared biological mechanisms (3,4). While cooccurrence of neurological features and conditions is frequently observed, very often, NDDs also include a variety of extra-neurological clinical signs such as hypotonia, dysmorphology, cardiologic or metabolic features, as well as gastrological problems such as constipation or diarrhea, which are specially frequent in ASD and ADHD (5)(6)(7), or immunological abnormalities (8,9). The recent advances in genotyping and sequencing technologies have propelled the identification of risk/causal genes, which has pointed to remarkable genetic heterogeneity among and within specific NDDs; for intellectual disability alone, pathogenic mutations in more than 1,000 genes have been confirmed in the SysID database (a systematic and manually curated catalog of IDassociated genes) (10).…”

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confidence: 99%

Heterogeneity in Fragile X Syndrome Highlights the Need for Precision Medicine-Based Treatments

Verdura¹,

Pérez-Cano²,

Sabido-Vera³

et al. 2021

Front. Psychiatry

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Fragile X syndrome (FXS) is the most frequent monogenic cause of autism or intellectual disability, and research on its pathogenetic mechanisms has provided important insights on this neurodevelopmental condition. Nevertheless, after 30 years of intense research, efforts to develop treatments have been mostly unsuccessful. The aim of this review is to compile evidence from existing research pointing to clinical, genetic, and therapeutic response heterogeneity in FXS and highlight the need of implementing precision medicine-based treatments. We comment on the high genetic and phenotypic heterogeneity present in FXS, as a contributing factor to the difficulties found during drug development. Given that several clinical trials have showed a non-negligeable fraction of positive responders to drugs targeting core FXS symptoms, we propose that success of clinical trials can be achieved by tackling the underlying heterogeneity in FXS by accurately stratifying patients into drug-responder subpopulations. These precision medicine-based approaches, which can be first applied to well-defined monogenic diseases such as FXS, can also serve to define drug responder profiles based on specific biomarkers or phenotypic features that can associate patients with different genetic backgrounds to a same candidate drug, thus repositioning a same drug for a larger number of patients with NDDs.

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mentioning

confidence: 99%

Heterogeneity in Fragile X Syndrome Highlights the Need for Precision Medicine-Based Treatments

Verdura¹,

Pérez-Cano²,

Sabido-Vera³

et al. 2021

Front. Psychiatry

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“…Ongoing methodological limitations have contributed to meaningful recommendations. Although the criteria used for diagnoses of CeD were closely followed, diagnosis of ADHD using ICD criteria was identified as a limitation, as it may have allowed for the inclusion of misdiagnoses and diagnoses [ 17 , 18 ]. This limitation may be explained by one of the subtypes of ADHD, called SCT.…”

Section: Discussionmentioning

confidence: 99%

“…In the ICD-10, the ADHD subtypes have separate codes, namely, inattentive (F90.0), hyperactive (F90.1), combined (F90.2), other (F90.8), and unspecified (F90.9)—whereas the ICD-9 has only three codes: combined (314.1), inattentive (314.00), and residual (314.8). These limitations have been discussed in previous studies [ 16 , 17 ]. Although the dimensions of ADHD are recognized as valid and clinically meaningful, some researchers have found that they are amenable to better specification, in particular, the inattentive type (IN), which can be phenotypically heterogeneous as it encompasses the sluggish cognitive tempo (SCT) subtype [ 18 , 19 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 93%

The Association between ADHD and Celiac Disease in Children

Gaur

2022

Children

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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. Background: 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. Methods: 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. Results: 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. Conclusion: There is an association between ADHD and celiac disease. The current methodological limitations will be lessened if we examine the subtypes of ADHD.

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“…Patients with IBS have a higher rate of anxiety, depression, and somatization [ 34 ]. Individuals with ADHD have more diagnosis of IBS with odds ratio 1.67 with 95%CI from 1.56 to 1.80 than those without ADHD [ 35 ]. Not only stress but also gut inflammation is likely a causative factor for IBS [ 36 ].…”

Section: Introductionmentioning

confidence: 99%

Maternal separation and TNBS-induced gut inflammation synergistically alter the sexually differentiated stress response in rats

Hasegawa

Saito-Nakaya

et al. 2023

BioPsychoSocial Med

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Background Neonatal maternal separation (MS) has been used to model long-lasting changes in behavior caused by neuroplastic changes associated with exposure to early-life stress. Earlier studies showed that transient gut inflammation can influence the development of irritable bowel syndrome (IBS). A prevailing paradigm of the etiology of IBS is that transient noxious events lead to long-lasting sensitization of the neural pain circuit, despite complete resolution of the initiating event. This study characterizes the changes in behaviors and neuroendocrine parameters after MS and early-phase trinitrobenzene sulfonic acid (TNBS)-induced colitis. We tested the hypothesis that MS and gut inflammation synergistically induce (1) hyperactivity in male rats and anxiety-like behaviors in female rats and (2) activation of the HPA axis in female rats and deactivation of the HPA axis in male rats after colorectal distention (CRD). Methods Male and female rat pups were separated from their dams for 180 min daily from postnatal day (PND) 2 to PND 14 (MS). Early-phase colitis was induced by colorectal administration with TNBS on PND 8. The elevated plus-maze test was performed at 7 weeks. Tonic CRD was performed at 60 mmHg for 15 min at 8 weeks. Plasma ACTH and serum corticosterone were measured at baseline or after the CRD. Analysis of variance was performed for comparison among controls, TNBS, MS, and MS + TNBS. Results In male rats, the time spent in open arms significantly differed among the groups (p < 0.005). The time spent in open arms in male MS + TNBS rats was significantly higher than that of controls (p < 0.009) or TNBS rats (p < 0.031, post hoc test). Female rats showed no difference in the time spent in open arms among the groups. MS and gut inflammation induced an increase in plasma ACTH in female rats but not in male rats at baseline. Conclusions These findings suggest that MS and gut inflammation synergistically induce hyperactive behavior or exaggerated hypothalamic–pituitary–adrenal axis function depending on sex.

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Attention deficit hyperactivity disorder and gastrointestinal morbidity in a large cohort of young adults

Cited by 17 publications

References 35 publications

Heterogeneity in Fragile X Syndrome Highlights the Need for Precision Medicine-Based Treatments

Heterogeneity in Fragile X Syndrome Highlights the Need for Precision Medicine-Based Treatments

The Association between ADHD and Celiac Disease in Children

Maternal separation and TNBS-induced gut inflammation synergistically alter the sexually differentiated stress response in rats

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