Wendy Shih

Association between Early Adverse Life Events and Irritable Bowel Syndrome

BACKGROUND & AIMS Although childhood and adult abuse are more prevalent among patients with irritable bowel syndrome (IBS) than healthy individuals (controls), other types of early adverse life events (EALs) have not been well characterized. We investigated whether different types of EALs, before age 18 years, are more prevalent among patients with IBS, and the effects of sex and nongastrointestinal symptoms on the relationship between EALs and IBS. METHODS EALs were evaluated in 294 IBS patients (79% women) and 435 controls (77% women) using the Early Trauma Inventory Self-Report Form, which delineates subcategories of general trauma and physical, emotional, and sexual abuse. Validated questionnaires assessed gastrointestinal, psychological, and somatic symptoms. RESULTS Compared with controls, IBS patients reported a higher prevalence of general trauma (78.5% vs 62.3%), physical punishment (60.6% vs 49.2%), emotional abuse (54.9% vs 27.0%), and sexual events (31.2% vs 17.9%) (all P < .001). These significant differences were observed mainly in women. Of the EAL domains, emotional abuse was the strongest predictor of IBS (P < .001). Eight of the 27 EAL items were significant (P < .001) and increased the odds of having IBS by 108% to 305%. Although EALs and psychological variables were related, EALs had an independent association with IBS (P = .04). CONCLUSIONS Various types of EALs are associated with the development of IBS-particularly among women. Psychological distress and somatic symptoms might contribute to this relationship. When appropriate, EALs and nongastrointestinal symptoms should be assessed in IBS patients.

Serum and Colonic Mucosal Immune Markers in Irritable Bowel Syndrome

OBJECTIVES:Low-grade colonic mucosal inflammation has been postulated to have an important role in the pathophysiology of irritable bowel syndrome (IBS). The objectives of this study were (i) to identify serum and tissue-based immunological and neuroendocrine markers associated with mucosal inflammation in male (M) and female (F) patients with non-post-infectious IBS (non-PI-IBS) compared with healthy controls and (ii) to assess possible correlations of such markers with IBS symptoms.METHODS:Sigmoid mucosal biopsies were obtained from 45 Rome II positive IBS patients without a history of PI-IBS (26 F, 35.5% IBS-C, 33.3% IBS-D, 31.1% IBS-A/M) and 41 healthy controls (22 F) in order to measure immunological markers (serum cytokine levels, colonic mucosal mRNA levels of cytokines, mucosal immune cell counts) and neuroendocrine markers associated with mucosal inflammation (corticotropin releasing factor- and neurokinin (NK)-related ligands and receptors, enterochromaffin cells). Symptoms were measured using validated questionnaires.RESULTS:Of all the serum and mucosal cytokines measured, only interleukin-10 (IL-10) mRNA expression showed a group difference, with female, but not male, patients showing lower levels compared with female controls (18.0±2.9 vs. 29.5±4.0, P=0.006). Mucosal mRNA expression of NK-1 receptor was significantly lower (1.15±0.19 vs. 2.66±0.56, P=0.008) in female, but not male, patients compared with healthy controls. No other significant differences were observed.CONCLUSIONS:Immune cell counts and levels of cytokines and neuropeptides that are associated with inflammation were not significantly elevated in the colonic mucosa of non-PI-IBS patients, and did not correlate with symptoms. Thus, these findings do not support that colonic mucosal inflammation consistently has a primary role in these patients. However, the finding of decreased IL-10 mRNA expression may be a possible biomarker of IBS and warrants further investigation.

Caregiver-Mediated Intervention for Low-Resourced Preschoolers With Autism: An RCT

OBJECTIVES: To compare 2 short-term, community caregiver training interventions for preschool-aged children with Autism Spectrum Disorder who had low resources. Low resource was defined by the US Department of Housing and Urban Development low-income index or 1 “indicator,” (eg, Medicaid eligibility). Child outcomes focused on joint engagement, joint attention, and play. METHODS: Participants included 112 families of a child who had Autism Spectrum Disorder who met criteria for being low-resourced and who were randomly assigned to 1 of 2 3-month interventions, group caregiver education or individualized caregiver-mediated intervention (CMM). Children were assessed for social communication skills pre- and post-treatment, and followed up at 3 months. RESULTS: All children improved in joint engagement and initiating joint attention, with significantly greater improvement by the CMM group. Outcomes on play skills were mixed, with improvement of symbolic play for the CMM group and no change in functional play skills. Joint engagement maintained over time for the CMM group, and initiating joint attention maintained for both groups over time. CONCLUSIONS: This study is among the first randomized trials comparing 2 active interventions with a large sample of low-resourced families. Results suggest improvements in core autism deficits of joint engagement, joint attention, and symbolic play with relatively brief, caregiver-mediated interventions, but additional support is necessary to maintain and generalize these gains over time.

The peer relationships of girls with ASD at school: Comparison to boys and girls with and without ASD

BACKGROUND This study examines the social relationships of elementary school children with high-functioning autism, focusing on how gender relates to social preferences and acceptance, social connections, reciprocal friendships, and rejection. METHOD Peer nomination data were analyzed for girls with and without ASD (n = 50) and boys with and without ASD (n = 50). Girls and boys with ASD were matched by age, gender, and IQ. Each child with ASD was matched by age and gender to a typically developing classmate. RESULTS Consistent with typically developing populations, children with ASD preferred, were accepted by, and primarily socialized with same-gender friends. With fewer nominations and social relationships, girls and boys with ASD appear more socially similar to each other than to the same-gender control group. Additionally, girls and boys with ASD showed higher rates of social exclusion than their typically developing peers. However, boys with ASD were more overtly socially excluded compared to girls with ASD, who seemed to be overlooked, rather than rejected. CONCLUSIONS Our data suggest a number of interesting findings in the social relationships of children with ASD in schools. Like typically developing populations, children with ASD identify with their own gender when socializing and choosing friends. But given the social differences between genders, it is likely that girls with ASD are experiencing social challenges that are different from boys with ASD. Therefore, gender is an important environmental factor to consider when planning social skills interventions at school.

Randomized controlled trial of parental responsiveness intervention for toddlers at high risk for autism.

This study tested the effects of a parent-mediated intervention on parental responsiveness with their toddlers at high risk for an autism spectrum disorder (ASD). Participants included caregivers and their 66 toddlers at high risk for ASD. Caregivers were randomized to 12 sessions of an individualized parent education intervention aimed at improving parental responsiveness or to a monitoring control group involving 4 sessions of behavioral support. Parental responsiveness and child outcomes were measured at three time points: at beginning and end of the 3-month treatment and at 12-months post-study entry. Parental responsiveness improved significantly in the treatment group but not the control group. However, parental responsiveness was not fully maintained at follow up. There were no treatment effects on child outcomes of joint attention or language. Children in both groups made significant developmental gains in cognition and language skills over one year. These results support parental responsiveness as an important intervention target given its general association with child outcomes in the extant literature; however, additional supports are likely needed to fully maintain the treatment effect and to affect child outcomes.

Characterization of symptoms in irritable bowel syndrome with mixed bowel habit pattern.

Irritable bowel syndrome (IBS) with mixed bowel habits (IBS‐M) is a heterogeneous subtype with varying symptoms of constipation and diarrhea, and has not been well characterized. We aimed to characterize gastrointestinal (GI) and non‐GI symptoms in IBS‐M patients from a US patient population, and to compare them with IBS with constipation (IBS‐C) and diarrhea (IBS‐D).

Children with Autism Spectrum Disorder and Social Skills Groups at School: A Randomized Trial Comparing Intervention Approach and Peer Composition.

BACKGROUND Peer relationships improve for children with autism spectrum disorder (ASD) in clinic-based social skills groups but rarely generalize to real world contexts. This study compares child outcomes of two social skills interventions conducted in schools with children in Kindergarten through fifth grade. METHOD Children with ASD were randomized to one of two interventions that varied on group composition (mixed typical and ASD vs. all ASD or social difficulties) and intervention approach (didactic SKILLS based vs. activity-based ENGAGE groups). Interventions were implemented at school for 8 weeks (16 sessions) with an 8-week follow-up. Innovative measures of peer nomination and playground peer engagement, as well as teacher reports of child behavior problems and teacher-child relationship were analyzed for 137 children with ASD across four sites. RESULTS On the primary outcome of social network connections from the peer nomination measure, there was no main effect of treatment, but there were moderator effects. Children with low teacher-child closeness or high conflict improved more in their social connections if they received the SKILLS intervention, whereas children with higher teacher-child closeness improved more if they received the ENGAGE intervention. Only two secondary outcome measures yielded significant effects of treatment. Children in the SKILLS groups increased peer engagement and decreased isolation during recess. Child behavior problems and teacher-child closeness moderated peer engagement such that children with higher behavior problems and lower closeness benefitted more from SKILLS groups. CONCLUSIONS These findings suggest that social skills groups conducted at school can affect both peer engagement during recess as well as peer acceptability. Child characteristics and teacher-child relationship prior to intervention yield important information on who might benefit from a specific social skills intervention.

Improving peer engagement of children with autism on the school playground: a randomized controlled trial.

This study aimed to test the effects of a psychosocial intervention, Remaking Recess, on peer engagement for children with autism spectrum disorder (ASD). Using a randomized, wait-list-controlled design, the intervention was implemented during recess at four elementary schools. The immediate treatment (IT) group consisted of 13 (2 female) elementary school students with ASD and the wait-list (WL) group contained 11 (4 female) students with ASD. All of the children with ASD were fully included in the general education program. Analyses revealed that time spent engaged with peers was significantly increased for the IT group and maintained over the follow-up. School playground staff in the IT group showed increased behaviors aimed at improving peer engagement for children with ASD compared to playground staff at the WL sites. These improvements did not maintain to follow-up. These results suggest that a low dose, brief intervention can be beneficial in increasing peer engagement for children with autism in inclusive settings, but continued support of playground staff is likely needed.

Autonomic Response to a Visceral Stressor is Dysregulated in Irritable Bowel Syndrome and Correlates with Duration of Disease

Previous studies reported altered autonomic nervous system (ANS) responses in irritable bowel syndrome (IBS) at baseline and to colonic balloon distension. This study examined heart rate variability (HRV) and plasma catecholamines as an index of ANS responsiveness in IBS during flexible sigmoidoscopy (FS) and explored associations of HRV with clinical measures.

Identification of a Functional TPH1 Polymorphism Associated With Irritable Bowel Syndrome Bowel Habit Subtypes

OBJECTIVES:Alterations in 5-hydroxytryptamine (5-HT) signaling have been implicated as a factor contributing to the altered bowel habit of irritable bowel syndrome (IBS) patients. Tryptophan hydroxylase 1 (TPH1) is the rate-limiting enzyme in enterochromaffin cell 5-HT biosynthesis. We hypothesized that genetic variants affecting TPH1 gene expression might alter intestinal 5-HT bioavailability and subsequently the propensity for distinct bowel habit subtypes in IBS. In this study, we assessed the only common TPH1 proximal promoter variant (−347C/A; rs7130929) and its association with bowel habit predominance in IBS.METHODS:Electrophoretic mobility shift assays were performed to assess whether the −347C/A-allele variant affects the DNA binding of nuclear factors. Genotype distribution was determined for 422 IBS patients subtyped using the Rome III criteria and for 495 healthy controls recruited from two university medical centers. Association with bowel habit was tested using a multinomial logistic regression model controlling for race, anxiety, depression, and study site.RESULTS:Early growth response factor 1 (EGR-1) bound with higher affinity to a site comprising the minor A-allele of single-nucleotide polymorphism (SNP) −347C/A. TPH1 genotype frequencies did not differ between IBS patients and controls overall. The CC genotype was more prevalent in the IBS-D subtype (47%) than in the IBS-C (25%) and IBS-M (37%) subtypes (P=0.039) after adjusting for race and other covariates. Colonic biopsies from a small cohort of IBS patients from one center were tested for higher TPH1 mRNA expression in samples with CC compared with the CA genotype, but the results did not reach statistical significance.CONCLUSIONS:The TPH1 promoter SNP −347C/A differentially binds EGR-1 and correlates with IBS bowel habit subtypes and possibly colonic TPH1 expression consistent with its role in modulating intestinal 5-HT signaling.