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Brief Report: Associations Between Self-injurious Behaviors and Abdominal Pain Among Individuals with ASD-Associated Disruptive Mutations
Abstract
Self-injurious behaviors (SIB) are elevated in autism spectrum disorder (ASD) and related genetic disorders, but the genetic and biological mechanisms that contribute to SIB in ASD are poorly understood. This study examined rates and predictors of SIB in 112 individuals with disruptive mutations to ASD-risk genes. Current SIB were reported in 30% of participants and associated with poorer cognitive and adaptive skills. History of severe abdominal pain predicted higher rates of SIB and SIB severity after controlling for age and adaptive behavior; individuals with a history of severe abdominal pain were eight times more likely to exhibit SIB than those with no history. Future research is needed to examine associations between genetic risk, pain, and SIB in this population.
... Other young individuals avoid sensory stimuli such as particular sounds, textures of play materials or clothing, and foods (Smith et al., 2005;Talay-Ongan & Wood, 2000), which may restrict learning opportunities that result from active exploration of the environment (Baranek et al., 2002). In addition, there are extreme consequences to sensory sensitivities, such as medical problems due to restricted diet, severe aggression or self-injurious behavior in response to sensory stimuli, or difficulty managing/accessing public spaces (Kurtz-Nelson et al., 2021;Talay-Ongan & Wood, 2000). ...
We aimed to identify unique constellations of sensory phenotypes for genetic etiologies associated with diagnoses of autism spectrum disorder (ASD) and intellectual disability (ID). Caregivers reported on sensory behaviors via the Sensory Profile for 290 participants (younger than 25 years of age) with ASD and/or ID diagnoses, of which ~ 70% have a known pathogenic genetic etiology. Caregivers endorsed poor registration (i.e., high sensory threshold, passive behaviors) for all genetic subgroups relative to an “idiopathic" comparison group with an ASD diagnosis and without a known genetic etiology. Genetic profiles indicated prominent sensory seeking in ADNP, CHD8, and DYRK1A, prominent sensory sensitivities in SCN2A, and fewer sensation avoidance behaviors in GRIN2B (relative to the idiopathic ASD comparison group).
... Возможно, заподозрить коморбидную патологию приемлемо по изменению состояния и усиливающейся стереотипности поведения, гиперактивности, повышению тревожности, агрессии, самоповреждению, которые коррелируют с выраженностью гастроинтестинальных симптомов [38]. Вопрос причинно-следственной связи между выраженностью поведенческих симптомов и появлением нарушений со стороны ЖКТ остается еще открытым. ...
Autism spectrum disorders (ASDs) are common neurodevelopmental disorders characterized by heterogeneity and high variability in severity of mental, neurological, and somatic symptoms. Such gastrointestinal malformations as abdominal pain, constipation, diarrhea, gastroesophageal reflux, nutritional disorders, intestinal microbiota disorders are common in autistic children. The association between the severity of gastrointestinal malformations and the severity of behavioral symptoms in ASDs was revealed. Early diagnosis and assessment of gastrointestinal malformations in ASDs is crucial for their further correction to optimize nutrition, to develop individual complex treatment and management with the involvement of multidisciplinary specialists.
... Persons with ID are prone to painful conditions, e.g. low impact fractures 13 or various abdominal conditions 14,15 . A series of studies has made it clear that persons with ID are at least as sensitive to pain as the general population 16-20 but signs of pain may be lacking or overlooked by caregivers [21][22][23] . ...
Intellectual disability (ID) affects approximately 1% of the population. Some patients with severe or profound ID are essentially non-communicating and therefore risk experiencing pain and distress without being able to notify their caregivers, which is a major health issue. This real-world proof of concept study aimed to see if heart rate (HR) monitoring could reveal whether non-communicating persons with ID experience acute pain or distress in their daily lives. We monitored HR in 14 non-communicating participants with ID in their daily environment to see if specific situations were associated with increased HR. We defined increased HR as being > 1 standard deviation above the daily mean and lasting > 5 s. In 11 out of 14 participants, increased HR indicated pain or distress in situations that were not previously suspected to be stressful, e.g. passive stretching of spastic limbs or being transported in patient lifts. Increased HR suggesting joy was detected in three participants (during car rides, movies). In some situations that were previously suspected to be stressful, absence of HR increase suggested absence of pain or distress. We conclude that HR monitoring may identify acute pain and distress in non-communicating persons with ID, allowing for improved health care for this patient group.
... low impact fractures 13 or various abdominal conditions. 14,15 A series of studies has made it clear that persons with ID are at least as sensitive to pain as the general population [16][17][18][19][20] but signs of pain may be lacking or overlooked by caregivers. [21][22][23] Structured interviews, questionnaires, and checklists aimed at caregivers have been developed to identify behavioral signs of pain in persons with ID. [24][25][26] However, even caregivers who are experienced observers may fail to identify painful conditions in non-communicating persons with ID. 17,27,28 Thus, there is a need to explore additional measures of pain detection that are applicable to a real-world situation. ...
Intellectual disability (ID) affects approximately 1% of the population. Some patients with severe or profound ID are essentially non-communicating and therefore risk experiencing pain and distress without being able to notify their caregivers, which is a major health issue. This study aimed to see if heart rate (HR) monitoring could reveal whether non-communicating persons with ID experience acute pain or distress in their daily lives. We monitored HR in 14 non-communicating participants with ID in their daily environment to see if specific situations were associated with increased HR. We defined increased HR as being > 1 standard deviation above the daily mean and lasting > 5 seconds. In 11 out of 14 participants, increased HR indicated pain or distress in situations that were not previously suspected to be stressful, e.g. passive stretching of spastic limbs or being transported in patient lifts. Increased HR suggesting joy was detected in three participants (during car rides, movies). In some situations that were previously suspected to be stressful, absence of HR increase suggested absence of pain or distress. We conclude that HR monitoring may identify acute pain and distress in non-communicating persons with ID, allowing for improved health care for this patient group.
Parler de trouble du comportement chez une personne « autiste » peut prêter à confusion. En effet les comportements non ordinaires sont fréquents chez ces personnes.
Une modification de comportements habituels, en fréquence ou en intensité; des comportements pouvant présenter des risques pour la personne ou son entourage font suspecter une souffrance qu’il convient d’évaluer afin de pouvoir la prendre en charge au mieux. La fréquence sous-estimée de pathologies somatiques et leur retard de prise en charge entraînent souvent des douleurs dont la seule expression peut être un trouble majeur du comportement ou un retrait inquiétant.
Dans les cas de personnes n’ayant pas le langage, ou un langage fonctionnel limité (de type écholalique par exemple), ayant aussi des particularités sensorielles, il est utile d’avoir recours à des outils d’hétéro-évaluation de la douleur [1].
Il s’agit de rendre lisible le visible [11].
Autism Spectrum Disorder (ASD) is a complex neurological and developmental disorder characterized by behavioral and social impairments as well as multiple co-occurring conditions, such as gastrointestinal abnormalities, dental/periodontal diseases, and allergies. The etiology of ASD likely involves interaction between genetic and environmental factors. Recent studies suggest that oral and gut microbiome play important roles in the pathogenesis of inflammation, immune dysfunction, and disruption of the gut–brain axis, which may contribute to ASD pathophysiology. The majority of previous studies used unrelated neurotypical individuals as controls, and they focused on the gut microbiome, with little attention paid to the oral flora. In this pilot study, we used a first degree-relative matched design combined with high fidelity 16S rRNA (ribosomal RNA) gene amplicon sequencing in order to characterize the oral and gut microbiotas of patients with ASD compared to neurotypical individuals, and explored the utility of microbiome markers for ASD diagnosis and subtyping of clinical comorbid conditions. Additionally, we aimed to develop microbiome biomarkers to monitor responses to a subsequent clinical trial using probiotics supplementation. We identified distinct features of gut and salivary microbiota that differed between ASD patients and neurotypical controls. We next explored the utility of some differentially enriched markers for ASD diagnosis and examined the association between the oral and gut microbiomes using network analysis. Due to the tremendous clinical heterogeneity of the ASD population, we explored the relationship between microbiome and clinical indices as an attempt to extract microbiome signatures assocociated with clinical subtypes, including allergies, abdominal pain, and abnormal dietary habits. The diagnosis of ASD currently relies on psychological testing with potentially high subjectivity. Given the emerging role that the oral and gut microbiome plays in systemic diseases, our study will provide preliminary evidence for developing microbial markers that can be used to diagnose or guide treatment of ASD and comorbid conditions. These preliminary results also serve as a starting point to test whether altering the oral and gut microbiome could improve co-morbid conditions in patients with ASD and further modify the core symptoms of ASD.
Individuals with autism spectrum disorder (ASD) are at heightened risk of psychiatric comorbidities across the lifespan, including elevated rates of internalizing, externalizing, and self-injurious behaviors. Identification of medical comorbidities that contribute to these concerns may elucidate mechanisms through which psychiatric concerns arise, as well as offer additional avenues for intervention. Gastrointestinal (GI) conditions are of particular interest, as they are prevalent among those with ASD, may share genetic or neurobiological etiologies with the core features of ASD, and are linked with psychiatric difficulties in the general population. In this paper, we draw on data from nearly 2,800 children and adolescents with ASD within the Simons Simplex Collection to characterize the unique contributions of (1) autism symptoms, (2) psychosocial factors (child's age, sex, verbal and nonverbal IQ, adaptive behavior, race, and household income), and (3) GI concerns with respect to multiple psychiatric outcomes. Multiple regression models revealed unique contributions of ASD symptoms and multiple psychosocial factors such as verbal IQ, adaptive behavior, and family income to internalizing, externalizing, and self-injurious behavior. In general, higher levels of psychiatric symptoms were associated with more ASD symptoms, higher verbal IQ, lower adaptive behavior skills, and lower family income. Furthermore, levels of GI symptoms accounted for unique variance in psychiatric outcomes over and above these other factors, linking increased GI problems with increased psychiatric symptoms in children with ASD. Taken together, results indicate that the presence and quantity of GI symptoms should be considered when evaluating psychiatric and behavioral concerns among children with ASD, and that treatment of GI conditions may be an important component in alleviating a broad array of mental health concerns in this group.
Background:
Haploinsufficiency of the forkhead-box protein P1 (FOXP1) gene leads to a neurodevelopmental disorder termed FOXP1 syndrome. Previous studies in individuals carryingFOXP1mutations and deletions have described the presence of autism spectrum disorder (ASD) traits, intellectual disability, language impairment, and psychiatric features. The goal of the present study was to comprehensively characterize the genetic and clinical spectrum of FOXP1 syndrome. This is the first study to prospectively examine the genotype-phenotype relationship in multiple individuals with FOXP1 syndrome, using a battery of standardized clinical assessments.
Methods:
Genetic and clinical data was obtained and analyzed from nine children and adolescents between the ages of 5-17 with mutations inFOXP1. Phenotypic characterization included gold standard ASD testing and norm-referenced measures of cognition, adaptive behavior, language, motor, and visual-motor integration skills. In addition, psychiatric, medical, neurological, and dysmorphology examinations were completed by a multidisciplinary team of clinicians. A comprehensive review of reported cases was also performed. All missense and in-frame mutations were mapped onto the three-dimensional structure of DNA-bound FOXP1.
Results:
We have identified nine de novo mutations, including three frameshift, one nonsense, one mutation in an essential splice site resulting in frameshift and insertion of a premature stop codon, three missense, and one in-frame deletion. Reviewing prior literature, we found seven instances of recurrent mutations and another 34 private mutations. The majority of pathogenic missense and in-frame mutations, including all four missense mutations in our cohort, lie in the DNA-binding domain. Through structural analyses, we show that the mutations perturb amino acids necessary for binding to the DNA or interfere with the domain swapping that mediates FOXP1 dimerization. Individuals with FOXP1 syndrome presented with delays in early motor and language milestones, language impairment (expressive language > receptive language), ASD symptoms, visual-motor integration deficits, and complex psychiatric presentations characterized by anxiety, obsessive-compulsive traits, attention deficits, and externalizing symptoms. Medical features included non-specific structural brain abnormalities and dysmorphic features, endocrine and gastrointestinal problems, sleep disturbances, and sinopulmonary infections.
Conclusions:
This study identifies novelFOXP1mutations associated with FOXP1 syndrome, identifies recurrent mutations, and demonstrates significant clustering of missense mutations in the DNA-binding domain. Clinical findings confirm the roleFOXP1plays in development across multiple domains of functioning. The genetic findings can be incorporated into clinical genetics practice to improve accurate genetic diagnosis of FOXP1 syndrome and the clinical findings can inform monitoring and treatment of individuals with FOXP1 syndrome.
Background
DYRK1A is a gene recurrently disrupted in 0.1–0.5% of the ASD population. A growing number of case reports with DYRK1A haploinsufficiency exhibit common phenotypic features including microcephaly, intellectual disability, speech delay, and facial dysmorphisms.
Methods
Phenotypic information from previously published DYRK1A cases (n = 51) and participants in an ongoing study at the University of Washington (UW, n = 10) were compiled. Frequencies of recurrent phenotypic features in this population were compared to features observed in a large sample with idiopathic ASD from the Simons Simplex Collection (n = 1981). UW DYRK1A cases were further characterized quantitatively and compared to a randomly subsampled set of idiopathic ASD cases matched on age and gender (n = 10) and to cases with an ASD-associated disruptive mutation to CHD8 (n = 12). Contribution of familial genetic background to clinical heterogeneity was assessed by comparing head circumference, IQ, and ASD-related symptoms of UW DYRK1A cases to their unaffected parents.
Results
DYRK1A haploinsufficiency results in a common phenotypic profile including intellectual disability, speech and motor difficulties, microcephaly, feeding difficulties, and vision abnormalities. Eighty-nine percent of DYRK1A cases ascertained for ASD presented with a constellation of five or more of these symptoms. When compared quantitatively, DYRK1A cases presented with significantly lower IQ and adaptive functioning compared to idiopathic cases and significantly smaller head size compared to both idiopathic and CHD8 cases. Phenotypic variability in parental head circumference, IQ, and ASD-related symptoms corresponded to observed variability in affected child phenotype.
Conclusions
Results confirm a core clinical phenotype for DYRK1A disruptions, with a combination of features that is distinct from idiopathic ASD. Cases with DYRK1A mutations are also distinguishable from disruptive mutations to CHD8 by head size. Measurable, quantitative characterization of DYRK1A haploinsufficiency illuminates clinical variability, which may be, in part, due to familial genetic background.
Electronic supplementary material
The online version of this article (10.1186/s13229-017-0173-5) contains supplementary material, which is available to authorized users.
We assessed potential factors associated with “current” or “ever” self-injurious behaviors, reported in the Autism Diagnostic Interview–Revised, among children with autism spectrum disorder (n = 692) from the Study to Explore Early Development. Data on factors examined were obtained from questionnaires, standardized clinical instruments, and birth certificates. We employed a log-binomial regression to assess these associations. Although most associations were quite similar for currently and ever exhibiting self-injurious behaviors, a few differences were noted. We documented previously unreported associations of current self-injurious behaviors with maternal age and cesarean delivery, and ever self-injurious behaviors with maternal age, child sex, gestational age, and maternal race. We also confirmed previously reported associations with adaptive skills, somatic conditions (sleep, gastrointestinal, and sensory abnormalities), and other behavioral problems. These findings are informative for clinical practice and future research.
Prevalence of self-injurious behavior (SIB) is as high as 50% among children with autism spectrum disorder (ASD). Identification of risk factors for the development of SIB is critical to early intervention and prevention. However, there is little empirical research utilizing a prospective design to identify early risk factors for SIB. The purpose of this study was to evaluate behavioral characteristics predicting SIB at age 2 years among 235 infants at high familial risk for ASD. Logistic regression results indicated that presence of SIB or proto-SIB and lower developmental functioning at age 12 months significantly predicted SIB at 24 months. A pattern of persistent SIB over this period was associated with a diagnosis of autism and poorer cognitive and adaptive outcomes.
Gene-disruptive mutations contribute to the biology of neurodevelopmental disorders (NDDs), but most of the related pathogenic genes are not known. We sequenced 208 candidate genes from >11,730 cases and >2,867 controls. We identified 91 genes, including 38 new NDD genes, with an excess of de novo mutations or private disruptive mutations in 5.7% of cases. Drosophila functional assays revealed a subset with increased involvement in NDDs. We identified 25 genes showing a bias for autism versus intellectual disability and highlighted a network associated with high-functioning autism (full-scale IQ >100). Clinical follow-up for NAA15, KMT5B, and ASH1L highlighted new syndromic and nonsyndromic forms of disease.
Copy number variants (CNVs) were detected and analyzed in 14 probands with autism and intellectual disability with self-injurious behavior (SIB) resulting in tissue damage. For each proband we obtained a clinical history and detailed behavioral descriptions. Genetic anomalies were observed in all probands, and likely clinical significance could be established in four cases. This included two cases having novel, de novo copy number variants and two cases having variants likely to have functional significance. These cases included segmental trisomy 14, segmental monosomy 21, and variants predicted to disrupt the function of ZEB2 (encoding a transcription factor) and HTR2C (encoding a serotonin receptor). Our results identify variants in regions previously implicated in intellectual disability and suggest candidate genes that could contribute to the etiology of SIB.
Background
The notion that stereotypic behaviours may be precursors of self-injurious behaviour (SIB) has been considered in the past, but the available empirical evidence is still inconsistent and ambiguous.Method
In a longitudinal study, we collected data on stereotypic behaviour and SIB from 160 infants and toddlers who were at-risk for developmental delay. Interviews were conducted with parents at three time points during a one-year span using the Behaviour Problems Inventory-01 which contains subscales for SIB and stereotyped behaviour. We used growth modelling to estimate linear trends in several models. Model fit was evaluated according to a combination of fit statistics as is recommended in structural equation or latent variable modelling approaches such as latent growth modelling.ResultsIn examining the relationship between stereotyped behaviours and SIB across time, the model that represented earlier stereotyped behaviour as predicting later SIB fit the data better than the other models.Conclusions
The findings corroborate the notion that stereotyped behaviour can be a precursor of SIB. If replicated by other studies, it makes a case for considering early intervening with stereotyped behaviour as a SIB prevention strategy.
Objective:
Pain assessment of individuals with autism spectrum disorder (ASD) is largely unexplored. The core deficits of ASD may interfere with this population's ability to effectively use traditional pain assessment tools. Accurate pain assessment is essential to providing quality care. The objective was to illuminate barriers to pain assessment in children with an ASD, describe novel methods to communicate about their pain experience, and identify vocabularies that hold meaning with respect to pain to better understand pain from their context.
Methods:
Qualitative descriptive study using semistructured interviews including interactive electronic technology to enhance communication. Subjects included children aged 6 to 17 years with ASD experiencing acute pain after a surgical procedure at a large urban tertiary children's hospital.
Results:
Based on the analysis of 40 interviews, participants consisted of 34 (85%) male, 29 (72.5%) non-Hispanic white with mean age 11.75 ± 3.36 years (range: 6-17). All subjects were able to describe and locate their pain but required a variety of approaches. Assessment preferences included minimal time spent focusing on pain and simplistic language and actions using terms familiar to each subject. Notably, subjects were able to reliably demonstrate understanding of graded response and seriation. Parent involvement was essential, both in helping interpret the child's needs and providing trusted support.
Conclusions:
Some children with ASD require an alternate interactive approach to pain assessment. Individualized consideration and estimation of pain assessment methods for use in this population may provide more meaningful interactions, ultimately guiding better pain management interventions.
Self-injurious behaviour is shown by a significant minority of children with developmental delay and has a substantial impact on child and carer wellbeing. Characteristics such as a greater degree of intellectual disability, autism spectrum disorder, some genetic syndromes and repetitive and impulsive behaviours are positively associated with self-injury. Prevalence generally increases with age into midadulthood and the behaviour is notably persistent.
In this review, we discuss the dominant causal theory of self-injury which draws on the principles of operant learning. We evaluate the utility of this theory to account for all empirical observations of self-injury.
A model of self-injury is presented that extends a previous model described by Guess and Carr. The new model integrates child characteristics and operant learning principles in a phenotype × environment paradigm to explain the variance in developmental trajectory of the severity of self-injury.
Behaviour dysregulation, as evidenced by the associations between self-injury, self-restraint, repetitive and impulsive behaviours, is identified as potentially influencing the severity and persistence of self-injury. Risk markers for self-injury are identified and the extended model indicates points of intervention and highlights the possibility of risk-related, targeted early intervention. The need for increased training of practitioners in the delivery of demonstrably effective interventions for self-injury is identified.
© 2015 Association for Child and Adolescent Mental Health.
Whole exome sequencing has proven to be a powerful tool for understanding the genetic architecture of human disease. Here we apply it to more than 2,500 simplex families, each having a child with an autistic spectrum disorder. By comparing affected to unaffected siblings, we show that 13% of de novo missense mutations and 43% of de novo likely gene-disrupting (LGD) mutations contribute to 12% and 9% of diagnoses, respectively. Including copy number variants, coding de novo mutations contribute to about 30% of all simplex and 45% of female diagnoses. Almost all LGD mutations occur opposite wild-type alleles. LGD targets in affected females significantly overlap the targets in males of lower intelligence quotient (IQ), but neither overlaps significantly with targets in males of higher IQ. We estimate that LGD mutation in about 400 genes can contribute to the joint class of affected females and males of lower IQ, with an overlapping and similar number of genes vulnerable to contributory missense mutation. LGD targets in the joint class overlap with published targets for intellectual disability and schizophrenia, and are enriched for chromatin modifiers, FMRP-associated genes and embryonically expressed genes. Most of the significance for the latter comes from affected females.
Autism spectrum disorders (ASD) comprise a group of neurodevelopmental abnormalities that begin in early childhood and are characterized by impairment of social communication and behavioral problems including restricted interests and repetitive behaviors. Several genes have been implicated in the pathogenesis of ASD, most of them are involved in neuronal synaptogenesis. A number of environmental factors and associated conditions such as gastrointestinal (GI) abnormalities and immune imbalance have been linked to the pathophysiology of ASD. According to the March 2012 report released by United States Centers for Disease Control and Prevention, the prevalence of ASD has sharply increased during the recent years and one out of 88 children suffers now from ASD symptoms. Although there is a strong genetic base for the disease, several associated factors could have a direct link to the pathogenesis of ASD or act as modifiers of the genes thus aggravating the initial problem. Many children suffering from ASD have GI problems such as abdominal pain, chronic diarrhea, constipation, vomiting, gastroesophageal reflux, and intestinal infections. A number of studies focusing on the intestinal mucosa, its permeability, abnormal gut development, leaky gut, and other GI problem raised many questions but studies were somehow inconclusive and an expert panel of American Academy of Pediatrics has strongly recommended further investigation in these areas. GI tract has a direct connection with the immune system and an imbalanced immune response is usually seen in ASD children. Maternal infection or autoimmune diseases have been suspected. Activation of the immune system during early development may have deleterious effect on various organs including the nervous system. In this review we revisited briefly the GI and immune system abnormalities and neuropeptide imbalance and their role in the pathophysiology of ASD and discussed some future research directions.
Autism spectrum disorder (ASD) is a heterogeneous disease in which efforts to define subtypes behav-iorally have met with limited success. Hypothesiz-ing that genetically based subtype identification may prove more productive, we resequenced the ASD-associated gene CHD8 in 3,730 children with developmental delay or ASD. We identified a total of 15 independent mutations; no truncating events were identified in 8,792 controls, including 2,289 un-affected siblings. In addition to a high likelihood of an ASD diagnosis among patients bearing CHD8 muta-tions, characteristics enriched in this group included macrocephaly, distinct faces, and gastrointestinal complaints. chd8 disruption in zebrafish recapitu-lates features of the human phenotype, including increased head size as a result of expansion of the forebrain/midbrain and impairment of gastrointes-tinal motility due to a reduction in postmitotic enteric neurons. Our findings indicate that CHD8 disrup-tions define a distinct ASD subtype and reveal unex-pected comorbidities between brain development and enteric innervation. INTRODUCTION
In pediatric settings, parents often raise concerns about possible gastrointestinal (GI) symptoms in autism spectrum disorder (ASD), yet the specificity of these concerns are not well studied.
To conduct a meta-analysis of research investigating GI symptoms among children with ASD.
We searched Medline, PsycINFO, and PubMed databases (1980-2012) in peer-reviewed journals. Analysis involved studies with a comparison group presenting quantitative data on GI symptoms using combinations of terms for ASD and GI indicators. The systematic search yielded 15 studies. We calculated effect sizes and 95% confidence intervals (CIs) using a random-effects model.
Children with ASD experience significantly more general GI symptoms than comparison groups, with a standardized mean difference of 0.82 (0.24) and a corresponding odds ratio (OR) of 4.42 (95% CI, 1.90-10.28). Analysis also indicated higher rates of diarrhea (OR, 3.63; 95% CI, 1.82-7.23), constipation (OR, 3.86; 95% CI, 2.23-6.71), and abdominal pain (OR, 2.45; 95% CI, 1.19-5.07).
Results indicate greater prevalence of GI symptoms among children with ASD compared with control children. Identified studies involved high methodological variability and lack of comprehensive data prohibited analysis of GI pathophysiologies (eg, gastroesophageal reflux) typically associated with organic etiologies, limiting conclusions about the underpinnings of the observed association. Future research must address critical questions about the causes and long-term impact of GI symptoms in ASD. Such analyses will require more systematic research and clinical activities, including improved diagnostic screening, standardized assessment, and exploration of potential moderators (eg, dietary restrictions).
To compare gastrointestinal (GI) problems among children with: (1) autism spectrum disorder (ASD), (2) developmental delay (DD) and (3) typical development (TD), GI symptom frequencies were obtained for 960 children from the CHildhood Autism Risks from Genetics and Environment (CHARGE) study. We also examined scores on five Aberrant Behavior Checklist (ABC) subscales comparing ASD children with high versus low frequency GI symptoms. 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. 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.
The objective of this study is to investigate whether parentally-reported gastro-intestinal (GI) symptoms are increased in a population-derived sample of children with autism spectrum disorders (ASD) compared to controls. Participants included 132 children with ASD and 81 with special educational needs (SEN) but no ASD, aged 10-14 years plus 82 typically developing (TD) children. Data were collected on GI symptoms, diet, cognitive abilities, and developmental histories. Nearly half (weighted rate 46.5 %) of children with ASD had at least one individual lifetime GI symptom compared with 21.8 % of TD children and 29.2 % of those with SEN. Children with ASD had more past and current GI symptoms than TD or SEN groups although fewer current symptoms were reported in all groups compared with the past. The ASD group had significantly increased past vomiting and diarrhoea compared with the TD group and more abdominal pain than the SEN group. The ASD group had more current constipation (when defined as bowel movement less than three times per week) and soiling than either the TD or SEN groups. No association was found between GI symptoms and intellectual ability, ASD severity, ASD regression or limited or faddy diet. Parents report more GI symptoms in children with ASD than children with either SEN or TD children but the frequency of reported symptoms is greater in the past than currently in all groups.
How does the behavioral expression of autism in fragile X syndrome (FXS + Aut) compare with idiopathic autism (iAut)? Although social impairments and restricted, repetitive behaviors are common to these variants of autism, closer examination of these symptom domains may reveal meaningful similarities and differences. To this end, the specific behaviors comprising the social and repetitive behavioral domains in young children with FXS + Aut and iAut were profiled.
Twenty-three male subjects 3 to 5 years old with FXS + Aut were matched by age to a group of 38 boys with iAut. Repetitive behavior was assessed using the Repetitive Behavior Scales-Revised. Social behavior was evaluated using Autism Diagnostic Observation Schedule social item severity scores.
Rates of stereotypy, self-injury, and sameness behaviors did not differ between groups, whereas compulsive and ritual behavior scores were significantly lower for subjects with FXS + Aut compared with those with iAut. Those with FXS + Aut scored significantly lower (less severe) than the iAut group on five Autism Diagnostic Observation Schedule measurements of social behavior: gaze integration, quality of social overtures, social smile, facial expressions, and response to joint attention.
The behavioral phenotype of FXS + Aut and iAut are most similar with respect to lower-order (motoric) restricted, repetitive behaviors and social approach, but differ in more complex forms of restricted, repetitive behaviors and some social response behaviors. These findings highlight the phenotypic heterogeneity of autism overall and its unique presentation in an etiologically distinct condition.
The ontogeny of self-injurious behaviour exhibited by young children with developmental delays or disabilities is due to a complex interaction between neurobiological and environmental variables. In this manuscript, the literature on emerging self-injury in the developmental disability population is reviewed with a focus on an operant conceptual model of how topographies of self-injurious behaviour can change structurally and become sensitive to various environmental consequences. Results of previous studies are reviewed in terms of extending our research focus from a reactive model of assessment and treatment of well-established cases of self-injury to an early intervention and prevention model.
It is well established that autism spectrum disorders (ASD) have a strong genetic component; however, for at least 70% of cases, the underlying genetic cause is unknown. Under the hypothesis that de novo mutations underlie a substantial fraction of the risk for developing ASD in families with no previous history of ASD or related phenotypes--so-called sporadic or simplex families--we sequenced all coding regions of the genome (the exome) for parent-child trios exhibiting sporadic ASD, including 189 new trios and 20 that were previously reported. Additionally, we also sequenced the exomes of 50 unaffected siblings corresponding to these new (n = 31) and previously reported trios (n = 19), for a total of 677 individual exomes from 209 families. Here we show that de novo point mutations are overwhelmingly paternal in origin (4:1 bias) and positively correlated with paternal age, consistent with the modest increased risk for children of older fathers to develop ASD. Moreover, 39% (49 of 126) of the most severe or disruptive de novo mutations map to a highly interconnected β-catenin/chromatin remodelling protein network ranked significantly for autism candidate genes. In proband exomes, recurrent protein-altering mutations were observed in two genes: CHD8 and NTNG1. Mutation screening of six candidate genes in 1,703 ASD probands identified additional de novo, protein-altering mutations in GRIN2B, LAMC3 and SCN1A. Combined with copy number variant (CNV) data, these results indicate extreme locus heterogeneity but also provide a target for future discovery, diagnostics and therapeutics.
While self-injurious behaviors (SIB) can cause significant morbidity for children with autism spectrum disorders (ASD), little is known about its associated risk factors. We assessed 7 factors that may influence self-injury in a large cohort of children with ASD: (a) atypical sensory processing; (b) impaired cognitive ability; (c) abnormal functional communication; (d) abnormal social functioning; (e) age; (f) the need for sameness; (g) rituals and compulsions. Half (52.3%, n = 126) of the children (n = 241, aged 2-19 years) demonstrated SIB. Abnormal sensory processing was the strongest single predictor of self-injury followed by sameness, impaired cognitive ability and social functioning. Since atypical sensory processing and sameness have a greater relative impact on SIB, treatment approaches that focus on these factors may be beneficial in reducing self-harm in children with ASD.
Self-injurious and aggressive behaviours are reported as components of some behavioural phenotypes but there are few studies comparing across syndrome groups. In this study we examined the prevalence of these behaviours and the associated person characteristics in seven genetic syndromes.
Questionnaire data on self-injury and aggression, mood, hyperactivity, autism spectrum disorder and repetitive behaviour were collected on Angelman (AS, n=104), Cornelia de Lange (CdLS, 101), Cri du Chat (CdCS, 58), Fragile X (FXS, 191), Lowe (LS, 56), Prader-Willi (PWS, 189) and Smith-Magenis (SMS, 42) syndromes.
A significantly higher prevalence of self-injury was evident in CdCS, CdLS, FXS, PWS, LS and SMS. The prevalence of aggression was significantly heightened in AS and SMS. Self-injury was associated with repetitive and impulsive behaviour in CdLS, FXS, PWS and LS. Impulsivity and overactivity were significantly higher in those showing aggression across all syndrome groups.
These data quantify the risk for self-injury and aggression in the syndromes studied with implications for early intervention. The associations between these behaviours and person characteristics both within and between syndromes warrant further research.
The prevalence of and risk factors for aggression were examined in 1,380 children and adolescents with autism spectrum disorders (ASD). Prevalence was high, with parents reporting that 68% had demonstrated aggression to a caregiver and 49% to non-caregivers. Overall, aggression was not associated with clinician observed severity of ASD symptoms, intellectual functioning, gender, marital status, parental educational level, or aspects of communication. Individuals who are younger, come from a higher income family, have more parent reported social/communication problems, or engage in repetitive behaviors were more likely to demonstrate aggression. Given the significant impact of aggression on individual and family outcomes, it is hoped that this knowledge will inform more targeted intervention efforts.
To examine the nature, prevalence and impact of chronic pain in adults with an intellectual disability (ID) based on carer report.
Postal questionnaires were sent to 250 care-givers and 157 responses were received (63%).
Chronic pain was reported in 13% of the sample (n = 21), 6.3% had pain in two sites and 2% had pain in three or more sites. Of those with chronic pain, 19 experienced mild chronic pain, while severe pain was reported for two service users. Pain problems were more prevalent in those with a Mild ID than in those with more severe disability, perhaps reflecting the ability of the Mild group to communicate about their pain. Non-prescription medication was the most common form of treatment and there was a notable absence of involvement of specialist pain services.
Given their increased risk for chronic pain, we concluded that pain in the ID population may be under-recognised and under-treated, especially in those with impaired capacity to communicate about their pain.
A functional analysis of the self-injurious behavior (SIB) of 3 adults with profound developmental disabilities showed that each engaged in SIB in more than one assessment condition. Such outcomes may result from a failure to isolate the variable maintaining SIB, or they may reflect multiple sources of control over SIB. In order to identify more clearly the determinants of SIB, each subject was exposed to a series of treatments appropriate to one or both of the apparent functions of SIB. These treatments, applied sequentially on baselines appropriate to each behavioral function, identified the maintaining variables for SIB through differential outcomes across baselines. Results indicated that the SIB of 2 subjects was multiply controlled, confirming the outcomes of the functional analysis. However, the SIB of the 3rd subject was eliminated using a treatment designed for a single function, suggesting spurious results of the original assessment. Alternative interpretations of undifferentiated assessment data are discussed, as are analysis and treatment issues related to multiply determined behavior disorders.
Functional analysis results for multiple topographies of aberrant behavior were graphed in an aggregate fashion and then separately for 48 clients. The results indicated that multiple topographies of behavior may be maintained by different contingencies. These results indicate that graphing functional analysis data in an aggregate fashion and then separately may improve the accuracy of their interpretation.
Children with autism spectrum disorder (ASD) are at risk for co-occurring medical conditions, many of which have also been reported among individuals with mutations in ASD-associated genes. This study examined rates of co-occurring medical conditions across 301 individuals with disruptive mutations to 1 of 18 ASD-risk genes in comparison to rates of conditions in an idiopathic ASD sample. Rates of gastrointestinal problems, seizures, physical anomalies, and immune problems were generally elevated, with significant differences in rates observed between groups. Results may inform medical care of individuals with ASD-associated mutations and research into mechanisms of co-occurring medical conditions in ASD.
Background:
Variants disruptive to CHD8 (which codes for the protein CHD8 [chromodomain-helicase-DNA-binding protein 8]) are among the most common mutations revealed by exome sequencing in autism spectrum disorder (ASD). Recent work has indicated that CHD8 plays a role in the regulation of other ASD-risk genes. However, it is unclear whether a possible shared genetic ontology extends to the phenotype.
Methods:
This study (N = 143; 42.7% female participants) investigated clinical and behavioral features of individuals ascertained for the presence of a known disruptive ASD-risk mutation that is 1) CHD8 (CHD8 group) (n = 15), 2) a gene targeted by CHD8 (target group) (n = 22), or 3) a gene without confirmed evidence of being targeted by CHD8 (other gene group) (n = 106).
Results:
Results indicated shared features between the CHD8 and target groups that included less severe adaptive deficits in communication skills, similar functional language, more social motivation challenges in those with ASD, larger head circumference, higher weight, and lower seizure prevalence relative to the other gene group.
Conclusions:
These similarities suggest broader genetic ontology accounts for aspects of phenotypic heterogeneity. Improved understanding of the relationships between related disruptive gene events may lead us to improved understanding of shared mechanisms and lead to more focused treatments for individuals with known genetic mutations.
Background
Self‐injurious behaviours (SIB) are concerning, maladaptive behaviours that commonly occur in people with neurodevelopmental conditions and delays but seem to be particularly prevalent in children and adults with autism spectrum disorder (ASD). There has been increasing research examining the risk markers associated with the presence of SIB in people with ASD. Some of the factors associated with SIB have included cognitive abilities, adaptive functioning deficits and behaviour regulation impairments (e.g. impulsivity and repetitive behaviours). However, many of the findings in the literature are mixed and only explain a small proportion of the variance contributing to SIB. Limitations in the previous literature have centred on lack of availability of large and diverse samples, restricted age ranges and constraints of measurement.
Method
This study characterises a clinic‐referred sample of children and adults currently presenting with and without SIB using a range of standardised and parent‐report measures. The sample includes 144 individuals with ASD between the ages of 2.5 and 60.1 years.
Results
After adjusting for multiple tests, none of the variables maintained statistical significance between the group of individuals with and without SIB, but medium to large effect sizes were noted. These variables include parent‐reported early motor and toileting delays and perinatal risk, and current cognitive and social impairment. The remaining variables, including current autism severity levels, early ASD symptomatology, impulsivity, executive functioning impairments, adaptive functioning, mood and anxiety, did not differ between those with and without current engagement in SIB.
Conclusions
Utilising a diverse clinic‐referred sample and standardised diagnostic tools, this study explored retrospective and current correlate risk markers of SIB in individuals with ASD. In addition to impairments in current functioning, specific early developmental delays and perinatal risk factors were preliminarily associated with the presence of SIB in individuals with ASD. Together these findings suggest that a set of specific characteristics may be related to both early risk and concurrent manifestation of SIB. Identifying this set of characteristics in early development may lead to faster identification and better intervention services, but future work utilising longitudinal design and multivariate analysis is warranted.
Background
In genome-wide screening studies for de novo mutations underlying autism and intellectual disability, mutations in the ADNP gene are consistently reported amongst the most frequent. ADNP mutations have been identified in children with autism spectrum disorder co-morbid with intellectual disability, facial features and deficits in multiple organ systems. However, a comprehensive clinical description of the Helsmoortel-Van der Aa syndrome is lacking.
Methods
We identified a worldwide cohort of 78 individuals with likely disruptive mutations in ADNP from January 2014 to October 2016 through systematic literature search, by contacting collaborators, and through direct interaction with parents. Clinicians filled in a structured questionnaire on genetic and clinical findings to enable genotype-phenotype correlations. Clinical photographs and specialist reports were gathered. Parents were interviewed to complement the written questionnaires.
Results
We report on the detailed clinical characterization of a large cohort of individuals with an ADNP mutation and demonstrate a distinctive combination of clinical features, including mild to severe intellectual disability, autism, severe speech and motor delay and common facial characteristics. Brain abnormalities, behavioral problems, sleep disturbance, epilepsy, hypotonia, visual problems, congenital heart defects, gastrointestinal problems, short stature and hormonal deficiencies are common co-morbidities. Strikingly, individuals with the recurrent p.Tyr719* mutation were more severely affected.
Conclusions
This overview defines the full clinical spectrum of individuals with ADNP mutations, a specific autism subtype. We show that individuals with mutations in ADNP have many overlapping clinical features, distinctive from other autism/ID syndromes. In addition, our data show preliminary evidence of a genotype-phenotype correlation.
Self-injurious behavior (SIB) is a relatively common behavior in individuals with intellectual disabilities (ID). Severe SIB can be devastating and potentially life-threatening. There is increasing attention for somatic substrates of behavior in genetic syndromes, and growing evidence of an association between pain and discomfort with SIB in people with ID and genetic syndromes. In this review on SIB phenomenology in people with ID in general and in twelve genetic syndromes, we summarize different SIB characteristics across these etiologically distinct entities and identify influencing factors. We demonstrate that the prevalence of SIB in several well-known genetic intellectual disability syndromes is noticeably higher than in individuals with ID in general, and that characteristics such as age of onset and topographies differ widely across syndromes. Each syndrome is caused by a mutation in a different gene, and this allows detection of several pathways that lead to SIB. Studying these with the behavioral consequences as specific aim will be an important step toward targeted early interventions and prevention.
Self-injurious behaviors (SIB) have been reported in more than 30 % of children with an autism spectrum disorder (ASD) in clinic-based studies. This study estimated the prevalence of SIB in a large population-based sample of children with ASD in the United States. A total of 8065 children who met the surveillance case definition for ASD in the Autism and Developmental Disabilities Monitoring (ADDM) Network during the 2000, 2006, and 2008 surveillance years were included. The presence of SIB was reported from available health and/or educational records by an expert clinician in ADDM Network. SIB prevalence averaged 27.7 % across all sites and surveillance years, with some variation between sites. Clinicians should inquire about SIB during assessments of children with ASD.
Self-injurious behaviors (SIB) are problematic for many children with autism spectrum disorders (ASD). Existing models to explain factors contributing to SIB fail to account for a large proportion of variance in SIB. This study attempted to explain a greater proportion of variance in SIB by addressing methodological/theoretical limitations in previous research using a sample of 2341 youth with ASD. The model comprised of predictors identified by the prior study continued to explain only a small proportion of variance in the SIB score (R
2 = .13). Revisions to the model failed to substantially improve model fit. Results suggest that psychological, cognitive, and behavioral factors alone do not adequately explain common measures of SIB and highlight the need for further research.
Background:
Gastrointestinal (GI) symptoms are frequently reported in children with Autism Spectrum Disorder (ASD), and an impact of GI comorbidity on ASD behavioral problems has been hypothesized.
Aims:
To explore the type and the prevalence of GI symptoms in ASD patients and typical development (TD) controls, and to investigate their possible association with behavioral problems.
Methods:
A total of 230 preschoolers were included in this study. Specifically, four groups of children were evaluated: ASD individuals suffering from GI symptoms (ASD/GI+), ASD subjects without GI symptoms (ASD/GI-), TD peers with (TD/GI+) and without (TD/GI-) GI symptoms. Parental report of behavioral problems and GI symptoms were assessed through the Child Behavior Check List 1½-5.
Results:
A significant higher percentage of ASD (37.4%) versus TD (14.8%) with GI symptoms was observed. 'Constipated' and 'Not-Eat' were the most frequent GI symptoms both in ASD and in TD groups, but they were evaluated as more severe in ASD patients. ASD/GI+ children had more anxiety problems, somatic complaints, externalizing and total problems than ASD/GI- individuals. TD/GI+ did not show more behavioral problems than TD/GI-.
Conclusion:
Development of evidence-based guidelines for identification of GI problems in ASD preschoolers is warranted. GI symptomatology should be accurately assessed, especially in ASD children with anxiety and/or externalizing behavioral problems.
* Abbreviations:
ASD — : autism spectrum disorder
GI — : gastrointestinal
5-HT — : serotonin
Autism spectrum disorders (ASDs) are a set of complex neurodevelopmental disorders defined behaviorally by impaired social interaction, delayed and disordered language, repetitive or stereotypic behavior, and a restricted range of interests. ASDs represent a significant public health issue with recent estimates indicating that as many as 1% of children in the United States are diagnosed with an ASD.1,2 Many individuals with ASDs have symptoms of associated medical conditions, including seizures, sleep problems, metabolic conditions, and gastrointestinal (GI) disorders, which have significant health, developmental, social, and educational impacts. Gastrointestinal complaints are a commonly reported concern for parents and may be related to problem behaviors and other medical issues such as dysregulated sleep (ATN Annual Registry Report, unpublished data, November 2009).3 Despite the magnitude of these issues, potential GI problems are not routinely considered in ASD evaluations. This likely reflects several factors, including variability in reported rates of GI disorders, controversies regarding the relationship between GI symptoms and the putative causes of autism, the limited verbal capacity of many ASD patients, and the lack of recognition by clinicians that certain behavioral manifestations in children with ASDs are indicators of GI problems (eg, pain, discomfort, or nausea).4–10
Whether GI issues in this population are directly related to the pathophysiology of autism, or are strictly a comorbid condition of ASD remains to be determined, but clinical practice and research to date indicate the important role of GI conditions in ASDs and their impact on children as well as their parents and clinicians.9
On November 15, 2009, a symposium addressing these issues was organized as an adjunct to the annual meeting of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. A …
Address correspondence to Daniel L. Coury, MD, Professor of Pediatrics and Psychiatry, The Ohio State University, Chief, Developmental & Behavioral Pediatrics, Nationwide Children's Hospital, 700 Children's Dr, Timken G-350, Columbus OH 43205-2696
Self-injurious behaviours (SIB) are highly prevalent in individuals with autism spectrum disorders (ASD) and have deleterious effects on the individual and their environment. The aim of this study was to examine SIB prevalence and associated features in a population of 152 adolescents with ASD and to determine risk factors for SIB.
The present study uses a subset of data of a longitudinal follow-up of 152 children with ASD. The presence of a low or high level of self-injury was assessed at adolescence through the Aberrant Behaviour Checklist completed by parents. Clinical and social variables regarding severity of autism symptoms, psychological development, adaptive behaviours, parental quality of life and total intervention time were collected during childhood (mean age = 5 years, SD = 1.6) and at adolescence (mean age = 15 years, SD = 1.3).
About 35.8% of adolescents with ASD in our sample displayed self-injury, which was frequently associated with other challenging behaviours and was related to severity of autism symptoms, adaptive skills, intellectual functioning and language level (P < 0.001). The main risk factor for SIB at adolescence was severity of autism symptoms (P = 0.04). Cognitive development during childhood was found to be a protective factor (P = 0.03) whereas at adolescence, the main protective factor was communicative abilities (P = 0.04).
These data showed that SIB remained highly prevalent at adolescence and yielded risk and protective factors for developing SIB at this period of life. Limitations and perspectives for future research are discussed.
© 2015 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.
The objective of this review is to consider the psychological (largely behavioral) and biological [neurochemical, medical (including genetic), and pharmacological] theories and approaches that contribute to current thinking about the etiology and treatment of self-injurious behavior (SIB) in individuals with autism spectrum disorder and/or intellectual disability. Algorithms for the assessment and treatment of SIB in this context, respectively, from a multidisciplinary, integrative perspective are proposed and challenges and opportunities that exist in clinical and research settings are discussed.
Objectives
To examine the one-year course of parent-reported abdominal pain in children with autism spectrum disorder (ASD), and to determine whether anxiety and sensory over-responsivity (SOR) contribute to the onset or remission of abdominal pain.
Methods
Participants included 225 children (ages 2–17) with ASD enrolled in the Autism Speaks Autism Treatment Network. Primary measures included the parent-reported GI Symptom Inventory Questionnaire, Child Behavior Checklist, and Short Sensory Profile.
Results
One-fourth (25.8%) experienced chronic abdominal pain (duration ≥3 months) at baseline, persisting at one-year follow-up for 86.7%. New onset pain occurred for 23.8% of those without baseline pain. Anxiety, SOR, and chronic abdominal pain were associated at baseline. SOR significantly predicted new onset pain, but neither anxiety nor SOR were predictors of pain remission.
Conclusions
Abdominal pain appears to be common and persistent among children with ASD. The relations among SOR, anxiety and abdominal pain offer information about potential underlying mechanisms.
Objective:
This study aimed to examine the prevalence and characteristics of psychiatry-related emergency department (ED) visits among children with an autism spectrum disorder (ASD), including the specific reason for visit, as well as the influence of insurance type.
Methods:
Data used for this cross-sectional, observational study were obtained from the 2008 National Emergency Department Sample, the largest all-payer ED database in the United States. Psychiatry-related visits to the ED among children with ASD were identified using International Classification of Diseases, Ninth Revision, billing codes. A total of 3,974,332 visits (unweighted) were present for youth 3-17 years, of which 13,191 involved a child with ASD.
Results:
Thirteen percent of visits among children with ASD were due to a psychiatric problem, as compared with 2% of all visits by youths without ASD. Results from the multivariate analyses revealed that the likelihood for a psychiatric ED visit was increased 9-fold (odds ratio [OR], 9.13; 95% confidence interval [CI], 8.61-9.70) among pediatric ASD visits, compared with non-ASD visits. Children with ASD who were covered by private insurance, compared with those with medical assistance, were at even greater risk for a psychiatric ED visit (OR, 1.58; 95% CI, 1.53-1.63). Visits among children with ASD were more likely to be due to externalizing (OR, 1.62; 95% CI, 1.44-1.83) and psychotic (OR, 1.93; 95% CI, 1.58-2.35) disorders compared with visits among non-ASD children.
Conclusions:
This study highlights the need for improving community-based psychiatric systems of care for youths with ASD to divert psychiatry-related ED visits, particularly for those children with private insurance.
Children with autism spectrum disorders (ASD) experience high rates of anxiety, sensory processing problems, and gastrointestinal (GI) problems; however, the associations among these symptoms in children with ASD have not been previously examined. The current study examined bivariate and multivariate relations among anxiety, sensory over-responsivity, and chronic GI problems in a sample of 2,973 children with ASD enrolled in the Autism Treatment Network (ages 2-17 years, 81.6 % male). Twenty-four percent of the sample experienced at least one type of chronic GI problem (constipation, abdominal pain, bloating, diarrhea, and/or nausea lasting three or more months). Children with each type of GI problem had significantly higher rates of both anxiety and sensory over-responsivity. Sensory over-responsivity and anxiety were highly associated, and each provided unique contributions to the prediction of chronic GI problems in logistic regression analyses. The results indicate that anxiety, sensory over-responsivity and GI problems are possibly interrelated phenomenon for children with ASD, and may have common underlying mechanisms.
The odds ratio (OR) is probably the most widely used index of effect size in epidemiological studies. The difficulty of interpreting the OR has troubled many clinical researchers and epidemiologists for a long time. We propose a new method for interpreting the size of the OR by relating it to differences in a normal standard deviate. Our calculations indicate that OR = 1.68, 3.47, and 6.71 are equivalent to Cohen's d = 0.2 (small), 0.5 (medium), and 0.8 (large), respectively, when disease rate is 1% in the nonexposed group; Cohen's d
Background:
In most individuals, injury results in activation of peripheral nociceptors (pain-sensing neurons of the peripheral nervous system) and amplification of central nervous system (CNS) pain pathways that serve as a disincentive to continue harmful behaviour; however, this may not be the case in some developmental disorders that cause intellectual disability (ID). Moreover, individuals affected by ID disorders may initiate self-injurious behaviour to address irritating or painful sensations. In normal individuals, a negative feedback loop decreases sensation of pain, which involves descending inhibitory neurons in the CNS that attenuate spinal nociceptive processing. If spinal nociceptive signalling is impaired in these developmental disorders, an exaggerated painful stimulus may be required in order to engage descending anti-nociceptive signals.
Methods:
Using electronic databases, we conducted a review of publications regarding the incidence of chronic pain or altered pain sensation in ID patients or corresponding preclinical models.
Results:
There is a body of evidence indicating that individuals with fragile X mental retardation and/or Rett syndrome have altered pain sensation. These findings in humans are supported by mechanistic studies using genetically modified mice harbouring mutations consistent with the human disease. Thus, once self-injurious behaviour is initiated, the signal to stop may be missing. Several developmental disorders that cause ID are associated with increased incidence of gastroesophageal reflux disease (GERD), which can cause severe visceral pain. Individuals affected by these disorders who also have GERD may self-injure as a mechanism to engage descending inhibitory circuits to quell visceral pain. In keeping with this hypothesis, pharmacological treatment of GERD has been shown to be effective for reducing self-injurious behaviour in some patients. Hence, multiple lines of evidence suggest aberrant nociceptive processing in developmental disorders that cause ID.
Conclusions:
There is evidence that pain pathways and pain amplification mechanisms are altered in several preclinical models of developmental disorders that cause ID. We present hypotheses regarding how impaired pain pathways or chronic pain might contribute to self-injurious behaviour. Studies evaluating the relationship between pain and self-injurious behaviour will provide better understanding of the mechanisms underlying self-injurious behaviour in the ID population and may lead to more effective treatments.
Self-injurious behavior (SIB) among individuals with intellectual and related neurodevelopmental disorders (IDD) is a clinical challenge and scientific puzzle. The physiological mechanisms regulating the sensory components of SIB remain a mystery with no clear understanding of the underlying pathophysiology. The central dogma regarding sensory processing in general and pain in particular among individuals with IDD and chronic SIB is that sensory processing is reduced and pain is absent or blunted. In this paper, recent findings challenging some of the conventional wisdom regarding pain and sensory function among individuals with IDD and SIB are reviewed. It seems that at least a subgroup of individuals with IDD and chronic SIB may be in a physiological state similar to neuropathic pain in which hyperalgesia is mediated by plasticity mechanisms regulating inflammatory, immune, and nociceptive systems. In response to repeated tissue damage associated with chronic self-injury, innate immune cells may be producing pro-inflammatory and pro-nociceptive cytokines that act on the brain to cause sickness-like behavior and sensitize primary sensory nerve afferents contributing to pain hypersensitivity (i.e., hyperalgesia).
In an effort to identify de novo genetic variants that contribute to the overall risk of autism, the Simons Foundation Autism Research Initiative (SFARI) has gathered a unique sample called the Simons Simplex Collection (SSC). More than 2000 families have been evaluated to date. On average, probands in the current sample exhibit moderate to severe autistic symptoms with relatively little intellectual disability. An interactive database has been created to facilitate correlations between clinical, genetic, and neurobiological data.
To determine the prevalence and impact of pediatric abdominal pain (AP).
Prospective cohort study (12/2005-06/2006), with gastrointestinal and other symptoms assessed weekly. Anxiety, depression, functional disability, quality of life, somatization, coping, school absenteeism and medical care were assessed in 237 students in the third through eighth grades (11.8 years; 134 girls) from 2 public schools weekly. Complete data were obtained on 4606 of 5175 (89%) possible questionnaires.
Seventy-two percent of children reported >1 somatic symptom weekly, and 45% of children reported >1 gastrointestinal symptom weekly. The weekly prevalence of AP was 38%, and 90% of children reported AP at least once. AP persisted >4 consecutive weeks in 52% of children and was associated with higher anxiety (P < .001) and depression (P < .001) scores and worse quality of life (P < .001). Twenty-three percent of children missed school for AP (average, 2.3 days), and 10% of parents of those children missed work (average, 1.9 days). Presence of AP (P < .001) was independently associated with school absences. Four children (2%) sought medical attention.
AP is common in school-age children and is associated with worse quality of life, psychological co-morbidities, school absenteeism, and parental work absences.
Systematic study of abnormal repetitive behaviors in autism has been lacking despite the diagnostic significance of such behavior. The occurrence of specific topographies of repetitive behaviors as well as their severity was assessed in individuals with mental retardation with and without autism. The occurrence of each behavior category, except dyskinesias, was higher in the autism group and autistic subjects exhibited a significantly greater number of topographies of stereotypy and compulsions. Both groups had significant patterns of repetitive behavior co-occurrence. Autistic subjects had significantly greater severity ratings for compulsions, stereotypy, and self-injury. Repetitive behavior severity also predicted severity of autism. Although abnormal repetition is not specific to autism, an elevated pattern of occurrence and severity appears to characterize the disorder.