Gastrointestinal Issues and Autism Spectrum Disorder. M Madra, R Ringel, & KG Margolis. Child and Adolescent Psychiatric Clinics of North America (2020).

Open Access- Read the full article at PubMed Central

Introduction

Gastrointestinal (GI) disorders are amongst the most common medical conditions that are comorbid with Autism spectrum disorders (ASD). Despite their prevalence, GI disorders are often overlooked. Untreated GI distress in children with ASD has been linked to many issues in this population, including sleep, behavioral and psychiatric disorders. It is thus essential to understand the presentations of GI problems in children with ASD. In this chapter we will discuss the GI disorders commonly associated with ASD, how they present, and studied risk factors.

Gastrointestinal Issues in Autism Spectrum Disorder. EY Hsiao. Harvard Review of Psychiatry (2014).

Read the full article at Hsaio Lab @ UCLA

Abstract

While autism spectrum disorder (ASD) is characterized by communication impairments, social abnormalities, and stereotypic behaviors, several medical comorbidities are observed in autistic individuals. Of these, gastrointestinal (GI) abnormalities are of particular interest given their reported prevalence and correlation with the severity of core autism-related behavioral abnormalities. This review discusses the GI pathologies seen in ASD individuals and the association of particular GI conditions with known genetic and environmental risk factors for autism. It further addresses how GI abnormalities can affect the neuropathological and behavioral features of ASD, as well as the development of autism-related endophenotypes such as immune  dysregulation, hyperserotonemia, and metabolic dysfunction. Finally, it presents emerging evidence for a gut-brain connection in autism, wherein GI dysfunction may contribute to the pathogenesis or severity of ASD symptoms

Gastrointestinal Symptoms in Autism Spectrum Disorder: A Review of the Literature on Ascertainment and Prevalence. C Holingue, C Newell, LC Lee, P Pasricha, & MD Fallin. Autism Research: Official Journal of the International Society for Autism Research (2018).

Open Access- Read the full article at PubMed Central

Lay Summary

We reviewed studies having to do with autism spectrum disorder and the gastrointestinal system, dating back to 1980. We found that the median prevalence of constipation was 22.2%, diarrhea 13.0%, and any symptom 46.8%. All symptoms had a wide range of estimates across studies. GI symptoms were associated with characteristics of the study, including  who measured the GI symptoms. We call for the development of a reliable and valid GI questionnaire for studies of ASD.

Gastrointestinal Symptoms in Autism Spectrum Disorder: A Systematic Review. G Leader, C Abberton, S Cunningham, K Gilmartin, M Grudzien, E Higgins, L Joshi, S Whelan, & A Mannion. Nutrients (2022).

Open Access- Read the full article at PubMed Central

Abstract

This systematic review aims to offer an updated understanding of the relationship between gastrointestinal symptoms (GIS) and autism spectrum disorder (ASD) in children and adolescents. The databases PsycINFO, Medline, Cinahl, and ERIC were searched using keywords, and relevant literature was hand-searched. Papers (n = 3319) were systematically screened and deemed eligible if
they were empirical studies published in English since 2014 and measured the GIS of individuals with ASD who were under 18 years old. Thirty studies were included in the final review. The study findings were synthesized under eight themes, including the prevalence and nature of GIS and their relationship with developmental regression, language and communication, ASD severity, challenging behavior, comorbid psychopathology, sleep problems, and sensory issues. The review found that GIS were common and that there was contradictory evidence concerning their relationship with co-occurring conditions. It also identified evidence of some causal relationships that support the existence of the gut–immune–brain pathways. Future research needs to use large prospective designs and objective and standardized GIS measurements to provide a nuanced understanding of GIS in the context of Autism Spectrum Disorder.

Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in Individuals with ASDs: A Consensus Report. T Buie, DB Campbell, GJ Fuchs, GT Furuta et al. Pediatrics (2010).

Read the full article Here

 Excerpt

Autism spectrum disorders (ASDs) are common and clinically heterogeneous neurodevelopmental disorders. Gastrointestinal disorders and associated symptoms are commonly reported in individuals with ASDs, but key issues such as the prevalence and best treatment of these conditions are incompletely understood. A central difficulty in recognizing and characterizing gastrointestinal dysfunction with ASDs is the communication difficulties experienced by many affected individuals. A multidisciplinary panel reviewed the medical literature with the aim of generating evidence-based recommendations for diagnostic evaluation and management of gastrointestinal problems in this patient population. The panel concluded that evidence-based recommendations are not yet available. The consensus expert opinion of the panel was that individuals with ASDs deserve the same thoroughness and standard of care in the diagnostic workup and treatment of gastrointestinal concerns as should occur for patients without ASDs. Care providers should be aware that problem behavior in patients with ASDs may be the primary or sole symptom of the underlying medical condition, including some gastrointestinal disorders. For these patients, integration of behavioral and medical care may be most beneficial. Priorities for future research are identified to advance our understanding and management of gastrointestinal disorders in persons with ASDs. Pediatrics 2010;125:S1–S1….

Associations between cytokines, endocrine stress response, and gastrointestinal symptoms in autism spectrum disorder. BJ Ferguson, S Marler, LL Altstein, EB Lee, MO Mazurek, A McLaughlin, EA Macklin, E McDonnell, DJ Davis, AM Belechia, CH Gillespie, CA Peterson, ML Bauman, KG Margolis, J Veenestra-VanderWeele, & DQ Beversdorf. Brain, Behavior, and Immunity (2016).

Open Access- Read the full article at PubMed Central

Abstract

Many children and adolescents with autism spectrum disorder (ASD) have significant  gastrointestinal (GI) symptoms, but the etiology is currently unknown. Some individuals with ASD show altered reactivity to stress and altered immune markers relative to typically-developing individuals, particularly stress-responsive cytokines including tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6). Acute and chronic stress is associated with the onset and exacerbation of GI symptoms in those without ASD. The present study examined whether GI symptoms in ASD were associated with increases in cortisol, a stress-associated endocrine marker, and TNF-α and IL-6 in response to stress. As hypothesized, a greater amount of lower GI tract symptoms were
significantly associated with post-stress cortisol concentration. The relationship between cortisol response to stress and GI functioning was greater for children who had a history of regressive autism. Exploratory analyses revealed significant correlations between cortisol response, intelligence, and inappropriate speech. In contrast, symptoms of the lower GI tract were not
associated with levels of TNF-α or IL-6. Significant correlations were found, however, between TNF-α and IL-6 and irritability, socialization, and intelligence. These findings suggest that individuals with ASD and symptoms of the lower GI tract may have an increased response to stress, but this effect is not associated with concomitant changes in TNF-α and IL-6. The relationship between cortisol stress response and lower GI tract symptoms in children with regressive autism, as well as the relationships between cortisol, IL-6, and intelligence in ASD, warrant further investigation.

 Emerging evidence for gene mutations driving both brain and gut dysfunction in autism spectrum disorder. B Niesler & GA Rappold. Molecular Psychiatry (2021).

Open Access- Read the full article at PubMed Central

Summary

Functional gastrointestinal disorders that are common in autism may derive from gene mutations previously linked to behavioral symptoms in autism spectrum disorder (ASD).

Intestinal dysmotility in a zebrafish (Danio rerio) shank3a; shank3b mutant model of autism. DM James, RA Kozol, Y Kajiwara, AL Whal, EC Storrs, JD Buxbaum, M Klein, B Moshiree, & JE Dallman. Molecular Autism (2019).

Open Access- Read the full article at PubMed Central

Abstract

Background and aims: Autism spectrum disorder (ASD) is currently estimated to affect more than 1% of the world population. For people with ASD, gastrointestinal (GI) distress is a commonly reported but a poorly understood co-occurring symptom. Here, we investigate the physiological basis for GI distress in ASD by studying gut function in a zebrafish model of Phelan-McDermid syndrome (PMS), a condition caused by mutations in the SHANK3 gene.

Methods: To generate a zebrafish model of PMS, we used CRISPR/Cas9 to introduce clinically related C-terminal frameshift mutations in shank3a and shank3b zebrafish paralogues (shank3abΔC). Because PMS is caused by SHANK3 haploinsufficiency, we assessed the digestive tract (DT) structure and function in zebrafish shank3abΔC+/− heterozygotes. Human SHANK3 mRNA was then used to rescue DT phenotypes in larval zebrafish.

Results: Significantly slower rates of DT peristaltic contractions (p < 0.001) with correspondingly prolonged passage time
(p < 0.004) occurred in shank3abΔC+/− mutants. Rescue injections of mRNA encoding the longest human SHANK3 isoform into shank3abΔC+/− mutants produced larvae with intestinal bulb emptying similar to wild type (WT), but still deficits in posterior intestinal motility. Serotonin-positive enteroendocrine cells (EECs) were significantly reduced in both shank3abΔC+/− and shank3abΔC−/− mutants (p < 0.05) while enteric neuron counts and overall structure of the DT epithelium, including goblet cell number, were unaffected in shank3abΔC+/− larvae.

Conclusions: Our data and rescue experiments support mutations in SHANK3 as causal for GI transit and motility abnormalities. Reductions in serotonin-positive EECs and serotonin-filled ENS boutons suggest an endocrine/neural component to this dysmotility. This is the first study to date demonstrating DT dysmotility in a zebrafish single gene mutant model of ASD.

Saliva RNA Biomarkers of Gastrointestinal Dysfunction in Children with Autism and Neurodevelopmental Disorders: Potential Implications for Precision Medicine. DQ Beversdorf, K Sohl, D Levitskiy, P Tennant, RP Goin-Kochel, RC Shaffer, A Confair, FA Middleton, & SD Hicks. Frontiers in Psychiatry (2021).

Open Access- Read the full article at PubMed Central

Abstract

Gastrointestinal (GI) disorders are common in children with neurodevelopmental disorders such as autism spectrum disorder (ASD). A limited understanding of the biologic factors that predispose this population to GI disorders has prevented development of individualized therapies to address this important medical issue. The goal of the current study was to determine if elements of the salivary micro-transcriptome could provide insight into the biologic perturbations unique to children with ASD-related GI disturbance. This cohort study included 898 children (ages 18–73 months) with ASD, non-ASD developmental delay (DD), or typical development (TD). The saliva micro-transcriptome of each child was assessed with RNA-seq. Outputs were aligned to
microbial and human databases. A Kruskal Wallis analysis of variance (ANOVA) was used to compare levels of 1821 micro-transcriptome features across neurodevelopmental status (ASD, DD, or TD) and GI presence or absence. An ANOVA was also used to compare micro-transcriptome levels among GI sub-groups (constipation, reflux, food intolerance, other GI condition, no GI condition), and to identify RNAs that differed among children taking three common GI medications (probiotics, reflux medication, or laxatives). Relationships between features identified in ANOVA testing were examined for associations with scores on the Autism Diagnostic Observation Schedule, 2nd Edition (ADOS-2) and the Vineland Adaptive Behavior Scales. GI disturbance rates were higher among children with ASD than peers with TD but were similar to those with DD. Five piwii interacting RNAs and three microbial RNAs displayed an interaction between developmental status and GI disturbance. Fifty-seven salivary RNAs differed between GI sub-groups–with microRNA differences between food intolerance and reflux groups being most common. Twelve microRNAs displayed an effect of GI disturbance and showed association with GI medication uses and measures of behavior. These 12 microRNAs displayed enrichment for 13 physiologic pathways, including metabolism/digestion long-term depression, and neurobiology of addiction. This study identifies salivary micro-transcriptome features with differential expression among children with ASD-related GI disturbance. A subset of the RNAs displays relationships with treatment modality and are associated with autistic behaviors. The pathobiologic targets of the micro-transcriptome markers may serve as targets for individualized therapeutic interventions aimed at easing pain and behavioral difficulties seen in ASD-related GI disturbance.

+/- T cell populations in children with autism spectrum disorder and co-morbid gastrointestinal symptoms. DR Rose, H Yang, M Careaga, K Angjustsiri, J Van de Water, & P Ashwood. Brain, Behavior, & Immunity – Health (2020).

Open Access- Read the full article at PubMed Central 

Abstract

Children with ASD are more likely to experience gastrointestinal (GI) symptoms than typically-developed children. Numerous studies have reported immune abnormalities and inflammatory profiles in the majority of individuals with ASD. Immune dysfunction is often hypothesized as a driving factor in many GI diseases and it has been suggested that it is more apparent in children with ASD that exhibit GI symptoms. In this study we sought to characterize peripheral T cell subsets in children with and without GI symptoms, compared to healthy typically developing children. Peripheral blood mononuclear cells were isolated from participants, who were categorized into three groups: children with ASD who experience GI symptoms (n ¼ 14), children with ASD who do not experience GI symptoms (n ¼ 10) and typically-developing children who do not experience GI symptoms (n ¼ 15). In order to be included in the GI group, GI symptoms such as diarrhea, constipation, and/or pain while defecating, had to be present in the child regularly for the past 6 months; likewise, in order to be placed in the no GI groups, bowel movements could not include the above symptoms present throughout development. Cells were assessed for surface markers and intracellular cytokines to identify T cell populations. Children with ASD and GI symptoms displayed elevated TH17 populations (0.757% +/- 0.313% compared to 0.297% +/- 0.197), while children with ASD who did not experience GI symptoms showed increased frequency of TH2 populations (2.02% +/- 1.08% compared to 1.01% +/- 0.58%). Both ASD groups showed evidence of reduced gut homing regulatory T cell populations compared to typically developing children (ASDGI:1.93% +/- 0.75% and ASDNoGI:1.85% +/- 0.89 compared to 2.93% +/- 1.16%). Children with ASD may have deficits in immune regulation that lead to differential inflammatory T cell subsets that could be linked to associated co-morbidities

 The Gut-Brain-Microbiome Axis and Its Link to Autism: Emerging Insights and the Potential of Zebrafish Models. DM James, EA Davidson, J Yanes, B Moshiree, & JE Dallman. Frontiers in Cell and Developmental Biology (2021).

Open Access- Read the full article at PubMed Central

Abstract

Research involving autism spectrum disorder (ASD) most frequently focuses on its key diagnostic criteria: restricted interests and repetitive behaviors, altered sensory perception, and communication impairments. These core criteria, however, are often accompanied by numerous comorbidities, many of which result in severe negative impacts on quality of life, including seizures, epilepsy, sleep disturbance, hypotonia, and GI distress. While ASD is a clinically heterogeneous disorder, gastrointestinal (GI) distress is among the most prevalent co-occurring symptom complex, manifesting in upward of 70% of all individuals with ASD. Consistent with this high prevalence, over a dozen family foundations that represent genetically distinct, molecularly defined forms of ASD have identified GI symptoms as an understudied area with significant negative impacts on quality of life for both individuals and their caregivers. Moreover, GI symptoms are also correlated with more pronounced irritability, social withdrawal, stereotypy, hyperactivity, and sleep disturbances, suggesting that they may exacerbate the defining behavioral symptoms of ASD. Despite these facts (and to the detriment of the community), GI distress remains largely unaddressed by ASD research and is frequently regarded as a symptomatic outcome rather than a potential contributory factor to the behavioral symptoms. Allowing for examination of both ASD’s impact on the central nervous system (CNS) as well as its impact on the GI tract and the associated microbiome, the zebrafish has recently emerged as a powerful tool to study ASD. This is in no small part due to the advantages zebrafish present as a model system: their precocious development, their small transparent larval form, and their parallels with humans in genetics and physiology. While ASD research centered on the CNS has leveraged these advantages, there has been a critical lack of GI-centric ASD research in zebrafish models, making a holistic view of the gut-brain-microbiome axis incomplete. Similarly, high-throughput ASD drug screens have recently been developed but primarily focus on CNS and behavioral impacts while potential GI impacts have not been investigated. In this review, we aim to explore the great promise of the zebrafish model for elucidating the roles of the gut-brain microbiome axis in ASD.

Developmental-behavioral profiles in children with autism spectrum disorder and co-occurring gastrointestinal symptoms. Restrepo, K Angkustsiri, SL Taylor, SJ Rogers, J Cabral, B Heath, A Hechtman, M Soloman, P Ashwood, DG Amaral, & CW Nordhal. Autism Research: Official Journal of the International Society for Autism Research (2020).

Open Access- Read the full article at PubMed Central

Lay Summary

ASD is characterized by challenges in social communication and repetitive behaviors. But, people with autism have many other difficulties including gastrointestinal problems. Children with ASD were three times more likely to experience GI symptoms than typically developing peers. Increased GI symptoms are associated with increased prob lem behaviors such as sleep problems, self injury, and body aches. Since GI symptoms are often treatable, it is important to recognize them as soon as possible. Both clinicians and parents should become more aware of the high occurrence of GI problems in autistic people

 Gastrointestinal dysfunction in autism: parental report, clinical evaluation, and associated factors. P Gorrindo, KC Williams, EB Lee, LS Walker, SG McGrew, & P Levitt. Autism Research: Official Journal of the International Society for Autism Research (2012).

Open Access- Read the full article at PubMed Central

Lay Abstract

Gastrointestinal dysfunction (GID) in children with autism spectrum disorder (ASD) is not well understood. Differences in factors associated with GID, such as eating habits, have been reported between ASD and non ASD populations, but relationships between these factors and GID have not been examined. There is also the possibility that what we do know about GID in ASD is influenced by parents’ perceptions of GID in their children. Although parents know their children best, they are not necessarily experts in determining GID. This study examined how well parents and pediatric gastrointestinal clinicians agree on GID in children, and
how factors thought to relate to GID in ASD, actually do relate to GID. 121 children were studied, in three groups: co-occurring ASD and GID, ASD without GID, and GID without ASD. Clinical evaluations by pediatric gastroenterologists validated parental reports of GID in ASD, with constipation the leading type of GID in ASD. Presence of GID in ASD was not associated with differences in diet or medications, but was associated with language and social impairments. These findings suggest that healthcare providers of children with ASD should be vigilant for GID, particularly in children who lack the ability to communicate verbally.

Gastrointestinal problems in children with autism, developmental delays or typical development. V Chaidez, RL Hansen, & I Hertz-Picciotto. Journal of Autism and Developmental Disorders (2014).

Open Access- Read the full article at PubMed Central

Abstract

Objectives: To compare GI problems among children with: 1) autism spectrum disorder (ASD), 2) developmental delay (DD) and 3) typical development (TD).

Methods: In 960 children from the CHildhood Autism Risks from Genetics and the Environment (CHARGE) study, we assessed GI symptom frequency. We examined scores on five Aberrant Behavior Checklist subscales comparing ASD children with high vs. low frequency GI symptoms.

Results: Compared to TD children, those with ASD (aOR 7.92[4.89–12.85]) and DD (aOR 4.55 [2.51–8.24]) were more likely to have at least one frequent GI symptom. Restricting to ASD children, those with frequent abdominal pain, gaseousness, diarrhea, constipation or pain on stooling scored worse on Irritability, Social Withdrawal, Stereotypy, and Hyperactivity compared with children having no frequent GI symptoms.

Conclusions: Frequent GI problems affect young children with ASD and DD more commonly than those with TD. Maladaptive behaviors correlate with GI problems, suggesting these comorbidities require attention.

Incidence of gastrointestinal symptoms in children with autism: a population-based study. SH Ibrahim, RG Voigt, SK Katusic, AL Weaver, & WJ Barbaresi. Pediatrics (2009).

Open Access- Read the full article at PubMed Central

Abstract

Objective: To determine whether children with autism have an increased incidence of gastrointestinal (GI) symptoms compared to matched controls in a population-based sample.

Design/Methods: In a previous study including all residents of Olmsted County, MN age < 21 years between 1976 and 1997, we identified 124 children who fulfilled DSM-IV based criteria for a research diagnosis of autism. Two controls were identified for each autism case, matched on gender, age, year of first registration, and duration of follow-up. Through the Rochester Epidemiology Project, all inpatient and outpatient diagnoses, including GI diagnoses, are indexed for computerized retrieval. GI diagnoses prior to 21 years of age were grouped into 5 categories: 1) constipation, 2) diarrhea, 3) abdominal bloating, discomfort, or irritability, 4) gastroesophageal reflux or vomiting, and 5) feeding issues or food selectivity. The cumulative incidence of each category was calculated using the Kaplan-Meier method. Cox proportional hazards models were fit to estimate the risk ratios (RR: cases versus controls) and corresponding ninety-five percent confidence intervals (95% CI).

Results: Subjects were followed to median ages of 18.2 (cases) and 18.7 (control) years. There were significant differences between autism cases and controls in the cumulative incidence by age 20 of constipation (33.9% versus 17.6%; RR=1.97; 95% CI: 1.25–3.10; p = 0.003) and feeding issues/ food selectivity (24.5 % versus 16.1%; RR=1.95; 95% CI: 1.18–3.24; p = 0.009). There was no significant association between autism case status and overall incidence of GI symptoms (RR=1.21), diarrhea (RR=1.34), gastroesophageal reflux/vomiting (RR=1.55), or abdominal bloating/discomfort/irritability (RR=1.03).

Conclusions: We found that children with autism had an increased incidence of constipation and feeding issues/food selectivity. Since these symptoms often have a behavioral etiology, our population-based data suggest a neurobehavioral rather than a primary organic gastrointestinal etiology, may account for the higher incidence of these GI symptoms in children with autism

 Psychophysiological Associations with Gastrointestinal Symptomatology in Autism Spectrum Disorder. BJ Ferguson, S Marler, LL Altstein, EB Lee, J Akers, K Sohl, A McLaughlin, K Hartnett, B Kille, M Mazurek, EA Macklin, E McDonnell, M Barstow, ML Bauman, KG Margolis, J Veenstra-VanderWeele, & DQ Beversdorf. Autism Research: Official Journal of the International Society for Autism Research (2017).

Open Access- Read the full article at PubMed Central

Abstract

Autism spectrum disorder (ASD) is often accompanied by gastrointestinal disturbances, which also may impact behavior. Alterations in autonomic nervous system functioning are also frequently observed in ASD. The relationship between these findings in ASD is not known. We examined the relationship between gastrointestinal symptomatology, examining upper and lower gastrointestinal tract symptomatology separately, and autonomic nervous system functioning, as assessed by heart rate variability and skin conductance level, in a sample of 120 individuals with ASD. Relationships with co-occurring medical and psychiatric symptoms were also examined. While the number of participants with significant upper gastrointestinal tract problems was small in this sample, 42.5% of participants met criteria for functional constipation, a disorder of the
lower gastrointestinal tract. Heart rate variability, a measure of parasympathetic modulation of cardiac activity, was found to be positively associated with lower gastrointestinal tract symptomatology at baseline. This relationship was particularly strong for participants with co-occurring diagnoses of anxiety disorder and for those with a history of regressive ASD or loss of
previously acquired skills. These findings suggest that autonomic function and gastrointestinal  problems are intertwined in children with ASD; although it is not possible to assess causality in this data set. Future work should examine the impact of treatment of gastrointestinal problems on autonomic function and anxiety, as well as the impact of anxiety treatment on gastrointestinal problems. Clinicians should be aware that gastrointestinal problems, anxiety, and autonomic dysfunction may cluster in children with ASD and should be addressed in a multidisciplinary treatment plan.

Gastrointestinal concerns in children with autism spectrum disorder: A qualitative study of family experiences. C Holingue, O Poku, D Pfeiffer, S Murray, & MD Fallin

Abstract

Gastrointestinal problems are common in the autism spectrum disorder community and may affect both the person with autism spectrum disorder and their families. However, little research is available on the experiences of families who have a child with both autism spectrum disorder and gastrointestinal symptoms. We held one-on-one interviews with 12 parents of children who had both autism spectrum disorder and gastrointestinal symptoms. We analyzed the raw text responses from these interviews and identified four main themes. First, parents shared that their children had trouble verbally communicating when they were experiencing gastrointestinal symptoms (Theme 1). This led parents to use bodily signs, such as changes in the stool, and non-verbal behaviors, such as irritability, to recognize when their child was having gastrointestinal symptoms. Next, gastrointestinal issues affected both the child’s well-being and their ability to attend class and extracurricular or social activities (Theme 2). The gastrointestinal issues also affected the family’s routines, overall well-being, and their ability to go out and do activities together as a family (Theme 3). Finally, parents often had challenges receiving accessible and quality healthcare for their child’s gastrointestinal problems (Theme 4). Together, these findings highlight the enormous burden that gastrointestinal symptoms have on the wellness of children with autism spectrum disorder and their families.

Vocal and motor behaviors as a possible expression of gastrointestinal problems in preschoolers with autism spectrum disorder. M Prosperi, E Santocchi, F Muratori, C Narducci, S Calderoni, R Tancredi, MA Morales, & L Guiducci. BMC Pediatrics (2019).

Open Access- Read the full article at PubMed Central

Abstract

Background: Gastrointestinal (GI) problems are one of the most frequent comorbidities in Autism Spectrum Disorder (ASD) but can be under-recognized due to the concomitant communication difficulties of this population. Accordingly, some associated behaviors (AB) such as verbal and motor behaviors (VB and MB, respectively) have been identified as a possible expression of an underlying GI problem and evaluated through an ad hoc questionnaire (the Associated Behaviors Questionnaire -ABQ-). The aims of this study were to investigate the presence and the type of AB in an Italian sample of ASD preschoolers, and to determine their correlations with GI problems.

Methods: We included 85 ASD preschoolers (mean age 4.14 years; SD 1.08) splitted into two groups (GI and No-GI) through the GI Severity Index instrument. AB were evaluated through the ABQ that includes VB, MB and Changes in overall state (C) clusters. Specific tools were administered to evaluate the ASD core ad associated symptoms, as well as the intellective and adaptive functioning.

Results: The GI group (N = 30) showed significantly higher scores in all the three ABQ areas (VB, MB and C) than the No-GI group (N = 55), with a positive correlation between GI symptoms and some specific AB as well as ABQ Total score. By dividing the whole sample in verbal and non-verbal individuals, both specific and shared AB emerged in the two groups.

Conclusions: Our results alert clinicians to consider behavioral manifestations as a possible expression of GI problems in ASD subjects. Therefore, the evaluation of AB may be useful to identify the presence of GI problems in the ASD populations, and especially in non-verbal ASD children.